This HANDBOOK is being updated by topic. For updates, please … · 2020-03-09 · 2 Antimicrobial Handbook GRAM NEGATIVE ISOLATES - % SUSCEPTIBLE Escherichia coli 81 68 93 97 97

AntimicrobialHandbook – 2012

0173-ColorCover2011 1/9/12, 3:18 PM1

This HANDBOOK is being updated by topic. For updates, please visit:

http://www.cdha.nshealth.ca/antimicrobial-stewardship

http://www.cdha.nshealth.ca/antimicrobial-stewardship

http://www.cdha.nshealth.ca/nsha-antimicrobial-stewardship

1Antimicrobial Handbook

Table of ContentsMicrobiology Susceptibility Reports 2009 ............................................................................ 2Guidelines for Interpretation of Gram Stain Resuilts ............................................................... 4Key Characteristics of Selected Organisms ........................................................................... 5Antibiotic Administration Considerations Selected Prescribing Criteria for Restricted Anti-infective Agent ................................... 7 Antibiotic Cost Awareness ........................................................................................... 9 Antibiotic Dosage Guidelines ....................................................................................... 11 Antibiotic Dosing in Obesity ........................................................................................ 15 Automatic Therapeutic Interchange ............................................................................ 20 Quinolone and Enteral Nutrition Policy ....................................................................... 21Clinical Guidelines Aminoglycoside Antibiotics-Dosing and Monitoring Guidelines .................................. 22 Amphotericin B Deoxycholate .................................................................................... 28 Amphotericin B Lipid Complex (ABLC) ....................................................................... 31 Bacteremia, Staphylococcus aureus ............................................................................ 32 CAPD Perionitis Management .................................................................................... 33 Candidemia Treatment of ........................................................................................... 38 Cellulitis ..................................................................................................................... 39 Clindamycin Intervention Project ............................................................................... 43 Clostridium Difficile-Associated Disease (CDAD), Treatment of ................................... 44 Endocarditis, Prevention of Bacterial ........................................................................... 47 Endocarditis, Treatment of Bacterial ........................................................................... 49 Febrile Neutropenia Febrile Neutropenia-High Risk Inpatient ................................................................ 54 Low Risk Febrile Neutropenia ................................................................................ 56 Empiric Therapy of Fungal Infections .......................................................................... 60 Immunization for Adults ............................................................................................. 64 Intra-abdominal Infections, Guidelines for Empiric Treatment ..................................... 68 Pelvic Inflammatory Disease ....................................................................................... 73 Penicillin Allergy ......................................................................................................... 74 Pentamidine-Suggested Dosing Guidelines ................................................................. 77 Pneumonia Empiric Therapy .................................................................................................... 78 Community-Acquired ............................................................................................ 79 Hospital-Acquired .................................................................................................. 81 Ventilator-Associated Pneumonia ........................................................................... 74 Sepsis ......................................................................................................................... 86 Splenectomy Vaccination Guidelines .......................................................................... 88 Surgical Prophylaxis ................................................................................................... 93 Trimethoprim Sulfamethoxazole Desensitization ......................................................... 94 Urinary Tract Infections (UTIs) Classification and Diagnosis ................................................................................... 104 Management of UTIs ............................................................................................. 105 Vancomycin Usage Guidelines ................................................................................................... 107 Dosage Guidelines ................................................................................................ 108Intravenous to Oral Step Down Sequential Antibiotic Therapy and Therapeutic Interchange ....................................... 110 Potential Savings Intravenous-to-Oral (IV to PO) Stepdown ........................................ 111 Bioavailability of Oral Antibiotics ................................................................................ 112Notes .............................................................................................................................. 113

Published by the Antimicrobial Agents Subcommittee, District Drugs and Therapeutics Committee © Revised 2012This handbook has been designed to aid practitioners at Capital Health in the appropriate utilization ofantimicrobials.

Editor Dr. Kathy Slayter in conjunction with the Antimicrobial Agents Subcommittee.

Access at http://cdhaintra.cdha.nshealth.ca/departmentservices/pharmacy/rxpublications.cfm

1-19 1/9/12, 3:05 PM1

Updated yearly-

Updated May 2019-

Updated April 2018-

Updated Nov 2018 -

Updated Feb 2019-

Updated Feb 2019-

Updated Feb 2019-

Updated 2017-

2 Antimicrobial Handbook

GRAM NEGATIVE ISOLATES - % SUSCEPTIBLE

Escherichia coli 81 68 93 97 97 84 92 96 99 97 92 96 71 85 96Klebsiella pneumoniae 92 IR 93 96 96 87 96 97 99 53 95 94 90 91 97Proteus mirabilis 93 82 94 99 100 91 97 96 99 IR 97 98 89 87 96Enterobacter cloacae IR IR IR IR IR IR 97 99 100 40 97 IR IR 91 99Citrobacter freundii IR IR IR 11 12 3 88 94 100 87 87 IR IR 81 97Serratia marcescens IR IR IR 50 21 IR 95 97 100 IR 94 50 49 99 85Klebsiella oxytoca 96 IR 51 100 100 49 98 99 100 93 99 96 95 98 99Morganella morganii IR IR IR 90 94 IR 92 86 100 IR 93 97 88 78 96Enterobacter aerogenes IR IR IR IR IR IR 100 100 100 15 100 IR IR 97 100

Amox

icill

in/c

lavu

alna

te

Ampi

cilli

n

Cefa

zolin

Cef

tazi

dim

e

Cef

tria

xone

Cep

hale

xin

Cip

roflo

xaci

n

Gen

tam

icin

Mer

open

em

Nitr

ofur

anto

in *

Nor

floxa

cin

Pipe

raci

llin/

tazo

bact

am

Pipe

raci

llin

TMP-

SMZ

Tobr

amyc

in

* For use in urinary tract infection only.IR - Usually not active either because of intrinsic or acquired resistance.

MicrobiologySusceptibility Reports May 2009

GRAM POSITIVE ISOLATES - % SUSCEPTIBLE

Staphylococcus aureus NT 81 81 76 64 81 64 98 99 97 98 100Coagulase negativestaphylococci NT 38 38 45 38 38 40 67 98 93 57 100Enterococcus faecalis 97 IR IR IR IR IR IR IR 99 30 IR 96 82Enterococcus faecium 12 IR IR IR IR IR IR IR NT 60 IR 65 99

Ampic

illin

Cefaz

olin

Ceph

alexin

Cipr

oflox

acin

Clind

amyc

in

Clox

acilli

n

Eryth

rom

ycin

Gent

amici

n

Nitro

furan

toin

*

Tetra

cycli

ne

TMP-

SMZ

Vanc

omyc

in

Gent

amici

n sy

nerg

y

* For use in urinary tract infection only.IR - Usually not active either because of intrinsic or acquired resistance.NT - Not tested.Methicillin resistant S. aureus strains are resistant to all penicillins, cephalosporins, andcarbapenems.

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UPDATED

Yearly


AFERMENTORS - % SUSCEPTIBLE

Pseudomonas aeruginosa 78 72 85 75 84 85 58 82 92 IR NT IRStenotrophomonas maltophilia 46 26 IR IR NT NT 16 14 13 0 38 98Acinetobacter baumannii 78 91 94 NT 89 60 NT 93 98 54 NT 90Burkholderia cepacia 22 3 IR NT NT NT IR IR IR IR IR 19

Cefta

zidim

e

Cipr

oflo

xacin

Imip

enem

Mer

open

em

Pipe

racil

lin/ta

zoba

ctam

Pipe

racil

lin

Amika

cin

Gent

amici

n

Tobr

amyc

in

Ceftr

iaxon

e

Tica

rcilli

n/cla

vulan

ate

TMP-

SMZ

IR - Usually not active either because of intrinsic or acquired resistance.NT - Not tested.N.B. - Specific susceptibilities should be consulted when they are available, as individualresults can be especially difficult to predict when the number is small of isolates tested.

MicrobiologySusceptibility Reports 2009 (cont’d)

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UPDATED

Yearly


Guidelines1 for Interpretation of Gram Stain Results

Gram-Positive Cocci (GPC) Pairs, chains, clusters:

- Staphylococcus sp Pairs, chains:

- Streptococcus sp - Enterococcus sp

Pairs, lancet-shaped: - Streptococcus pneumoniae

Pairs: - Enterococcus sp

Gram-Positive Bacilli (GPB) Diphtheroids:

- Small, pleomorphic:> Corynebacterium sp > Propionibacterium (anaerobe)

Large, with spores: - Clostridium sp - Bacillus sp

Branching, beaded, rods: - Nocardia sp - Actinomyces sp (anaerobe)

Other: - Listeria sp (blood/cerebrospinal fluid) - Lactobacillus sp (vaginal/blood)

Gram-Negative Cocci (GNC) Diplococci

- Pairs:> Neisseria meningitidis > Neisseria gonorrhoeae > Moraxella catarrhalis

Other: - Acinetobacter sp

Gram-Negative Bacilli (GNB) Enterobacteriaceae:

- Escherichia coli - Serratia sp - Klebsiella sp - Enterobacter sp - Citrobacter sp

Nonfermentative: - Pseudomonas aeruginosa - Stenotrophomonas (Xanthomonas) maltophilia - Many others

Haemophilus influenzae Bacteroides fragilis group (anaerobe) Fusiform (long, pointed):

- Fusobacterium sp (anaerobe) - Capnocytophyga sp

1These guidelines are not definitive but presumptive for the identification of organisms on gram stain. Treatment will depend on the quality of the specimen and appropriate clinical evaluation.

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Key Characteristics of Selected Organisms

Gram-Positive Cocci (GPC) Catalase-positive:

- Staphylococcus sp Catalase-negative:

- Enterococcus sp - Streptococcus sp (chains) - Micrococcus sp (usually insignificant)

Coagulase-positive: - Staphylococcus aureus

Coagulase-negative: - Coagulase-negative staphylococci (CNS):

> Blood: Staphylococcus epidermidis or CNS > Urine: Staphylococcus saprophyticus > Staphylococcus lugdunensis4

Gram-Positive Bacilli (GPB) Diphtheroids:

- May be Corynebacterium sp: often blood culture contaminants

- Corynebacterium jeikeium: resistant to many agents except vancomycin

Anaerobic diphtheroids: Propionibacterium acnes Bacillus sp: Bacillus anthracis: non-motile and non- -

hemolytic; Bacillus subtilisspores

Listeria monocytogenes: cerebrospinal fluid, blood Lactobacillus sp: vaginal flora, rarely in blood Nocardia sp: Branching, beaded; partial acid-fast-positive Rapid growing mycobacteria:

- Mycobacterium fortuitum - Mycobacterium chelonae/abscessus

Gram-Negative Bacilli (GNB) Other:

- Haemophilus influenzae (coccobacillary); requires supplements/special media (chocolate agar plate)

Gram-Negative Cocci Neisseria meningitidis Neisseria gonorrhoeae Moraxella (Branhamella) catarrhalis Acinetobacter sp1

Gram-Negative Bacilli (GNB) Lactose-positive:

- Escherichia coli - Klebsiella pneumoniae (mucoid) - Enterobacter sp2 - Citrobacter sp2

Lactose-negative/oxidase-negative: - Proteus mirabilis: indole-negative - Proteus vulgaris: indole-positive - Providencia sp - Morganella morganii - Serratia sp3 - Salmonella sp - Shigella sp - Acinetobacter sp1 - Stenotrophomonas (Xanthomonas) maltophilia

(nonfermenter) Lactose-negative/oxidase-positive:

- Pseudomonas aeruginosa (green; - - Aeromonas hydrophila (may be lactose-positive) - Rare:

> Other Pseudomonas sp > Moraxella sp1 > Alcaligenes sp > Burkholderia sp

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Key Characteristics of Selected Organisms (continued)

Fungi Moulds:

- Aseptate hyphae:> Zygomycetes, such as:

- Rhizopus sp - Mucor

- Septate hyphae:> Brown pigment (phaeohyphomycetes), such as:

- Bipolaris sp - Exserohilum sp - Alternaria sp - Curvularia sp - Sporothrix schenckii -

> Non-brown pigmented (hyalohyphomycetes, most common), such as:

- Aspergillus sp (Aspergillus fumigatus, Aspergillus flavus) - Fusarium sp - Penicillium sp - Paecilomyces sp - Dermatophytes

- Thermally dimorphic (yeast in tissue, mould in lab): > Histoplasma capsulatum (slow growing) > Blastomyces dermatitidis > Coccidioides immitis

Yeast: - Candida sp; Candida albicans if germ tube-positive - Cryptococcus sp (no pseudohyphae); Cryptococcus

neoformans if latex- or CAD-positive - Candida glabrata - Trichosporon sp - Rhodotorula, Saccharomyces sp

Anaerobes GNB:

- Bacteriodes sp (Bacteriodes fragilis) - Fusobacterium sp

GNC:- Veillonella sp

GPC:- Peptostreptococcus sp

GPB:- Propionibacterium acnes - Clostridium sp (spores) - Actinomyces sp (branching, filamentous) - Lactobacillus sp - Eubacterium sp - Bifidobacterium sp

1 May be either bacillary or coccoid. 2 May be lactose negative. 3 May produce red pigment and appear lactose-positive initially. 4 Clinically can act as Staphylococcus aureus; laboratory results will reflect this by using MIC interpretation for Staphylococcus aureus.

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Selected Prescribing Criteria ForRestricted Anti-infective AgentsCefotaxime and ceftriaxone (Cefotaxime should be used in placeof ceftriaxone for patients with biliary sludging or severe diarrhea)� Treatment of nosocomial pneumonia.� EMPIRIC therapy of severely ill patients with suspected Gram

negative infection.� Documented Gram negative infection resistant to 1st and 2nd

generation cephalosporins in patients who cannot receiveaminoglycosides.

� Meningitis.� Spontaneous bacterial peritonitis, community-acquired

secondary peritonitis (or hospital acquired with no previousantimicrobial therapy), or intra-abdominal abscess.

� Community acquired pneumonia in patients treated with afluoroquinolone in the last 3 months.

� Therapy for low risk febrile neutropenic patients.� Other indications on recommendation by the Division of

Infectious Diseases.

Ceftazidime� Treatment of documented Pseudomonas infections.� Empiric therapy for presumed Pseudomonas infections in febrile

neutropenic and cystic fibrosis patients.� Other indications on recommendation by the Division of


Ciprofloxacin IVPatients unable to take oral ciprofloxacin and one of:� Treatment of a documented Gram-negative infection due to an

organism resistant to other antibiotics or when anotherantibiotic is contraindicated.

� Treatment of respiratory infections in cystic fibrosis.� Empiric therapy of ICU nosocomial pneumonia where

Pseudomonas or other resistant Gram-negative infections aresuspected.

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� Therapy of high-risk febrile neutropenia for patients with asevere B-lactam allergy.

� Treatment of intra-abdominal infections in patients who cannotreceive penicillin or aminoglycoside-containing regimens.

� Peritonitis protocol for peritoneal dialysis patients.� Other indications on recommendation by the Division of


Imipenem� Treatment of resistant infections in cystic fibrosis patients.� Treatment of documented resistant infections or where

resistance to piperacillin-tazobactam or third-generationcephalosporins is likely.

� Other indications on recommendation by the Division ofInfectious Diseases.

Piperacillin-tazobactam� As a single agent for the treatment of serious Gram-negative or

polymicrobial infections, including mixed aerobic and anaerobicinfections, where the use of other agents is not appropriatebecause of resistance, contraindications or adverse events.

� Treatment of high risk febrile neutropenia.� Other indications on recommendation by the Division of


1-19 1/9/12, 3:05 PM8


Name Route Average Adult Dosage Regimen $ per dose $ per day

Aminoglycosides

Amikacin IV/IM 1000 mg (15 mg/kg) q24h $60.33 $60.33

Gentamicin IV/IM 400 mg (6 mg/kg) q24h $11.85 $11.85

Streptomycin IV 1000 mg q12h $8.40 $16.80

Tobramycin IV/IM 400 mg (6 mg/kg) q24h $19.43 $19.43

Antifungals

Amphotericin B IV 50 mg q24h $56.71 $56.71

ABLC* (amphotericin B lipid complex) IV 400 mg q24h $794.75 $794.75

Fluconazole po 200 mg q24h $5.24 $5.24

Fluconazole IV 200 mg q24h $14.15 $14.15

Itraconazole Oral Solution po 200 mg q24h $16.02 $16.02

Ketoconazole po 400 mg q24h $0.80 $0.80

Micafungin* IV 100 mg q24h $100.00 $100.00

Voriconazole* IV 400 mg q12h $280.00 $560.00

Voriconazole* po 200 mg q12h $47.50 $95.00

Antivirals

Acyclovir IV 350 mg (5 mg/kg) q8h $10.65 $31.95

Acyclovir po 200 mg 5 x per day $0.30 $1.50

Acyclovir po 800 mg 5 x per day $1.14 $5.70

Amantadine po 100 mg q12h $0.12 $0.25

Ganciclovir Implant 1 implant q5-8months

Oseltamavir (prophylaxis) po 75 mg q24h $3.90 $3.90

Oseltamavir po 75 mg q12h $3.90 $7.80

Valacyclovir po 500 mg q12h $3.31 $6.62

Valganciclovir po 900 mg q12h $44.82 $89.64

Cephalosporins

1st Generation

CeFAZolin IV/IM 1 g q8h $2.39 $7.17

CephALEXin po 500 mg q6h $0.16 $0.64

2nd Generation

CefUROXime axetil po 500 mg q12h $0.98 $1.96

CefUROXime Na IV/IM 750 mg q8h $4.55 $13.65

3rd Generation

CefoTAXime* IV/IM 1 g q8h $7.40 $22.20

CeftAZIDime* IV/IM 1 g q6h $6.40 $25.76

CefTRIAXone* IV/IM 1 g q24h $2.95 $2.95

CeFIXime po 400 mg q24h x 1 $3.18 $3.18

Fluoroquinolones

Ciprofloxacin* po 500 mg q12h $0.34 $0.68

Ciprofloxacin* IV 400 mg q12h $9.50 $19.00

Levofloxacin* po 500 mg q24h $2.80 $2.80

Levofloxacin* IV 500 mg q24h $34.00 $34.00

Antibiotic Cost Awareness

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Antibiotic Cost Awareness (cont’d)

Costs include additional $1.15/dose for IV minibag; Dose per kg based on a 70 kg adult* Restricted antimicrobial

Name Route Average Adult Dosage Regimen $ per dose $ per day

Penicillins

Amoxicillin po 500 mg q8h $0.06 $0.24

Amoxicillin/Clavulanate po 875 mg/125 mg q12h $0.61 $1.22

Ampicillin IV/IM 1 g q6h $1.90 $7.60

Cloxacillin po 500 mg q6h $0.08 $0.32

Cloxacillin IV/IM 2 g q6h $4.77 $19.08

Penicillin G Na IV/IM 3 MU q4h $2.64 $15.84

Penicillin VK po 300 mg q6h $0.02 $0.08

Piperacillin IV/IM 3 g q6h $9.28 $37.12

Piperacillin/Tazobactam* IV 3.375 g q6h $7.64 $30.56

Ticarcillin/Clavulanate* IV 3.1 g q6h $11.25 $44.98

Tetracyclines

Doxycycline po 100 mg q12h $0.22 $0.44

Doxycycline† IV 100 mg q12h $15.15 $30.30

Tetracycline po 250 mg q6h $0.05 $0.20

Macrolides

Azithromycin po 500 mg on day one, q24h $1.89 $1.89

then 250 mg for 4 days

Azithromycin IV 500 mg q24h $23.92 $23.92

Azithromycin (MAC) po 1200 mg q weekly $15.25 N/A

Clarithromycin po 250 mg q12h $0.75 $1.50

Erythromycin po 500 mg q6h $0.16 $0.65

Miscellaneous

Chloramphenicol IV 1000 mg q6h $15.65 $62.60

Clindamycin po 300 mg q6h $0.31 $1.24

Clindamycin IV 600 mg q8h $4.27 $12.81

Dapsone po 100 mg q24h $0.41 $0.41

Daptomycin IV 6-8 mg/kg q24h $140.00 $140.00

Linezolid* po 600 mg q12h $70.64 $141.28

Linezolid* IV 600 mg q12h $95.51 $191.02

Imipenem IV 500 mg q6h $6.10 $24.40

Metronidazole IV 500 mg 12h $1.57 $3.14

Metronidazole po 500 mg q8h $0.04 $0.12

Nitrofurantoin po 50 mg q6h $0.11 $0.44

Trimethoprim/Sulfamethoxazole po 1 DS q12h $0.06 $0.12

Trimethoprim/Sulfamethoxazole IV 10 mL q12h $7.55 $30.20 (16 mg & 80 mg/5 mL)

Trimethoprim/Sulfamethoxazole IV 10 mL q6h $7.55 $30.20 (16 mg & 80 mg/5 mL) for PCP

Vancomycin IV 1 g q12h $10.33 $20.66

Vancomycin* po 125 mg q6h $1.15 $4.59

1-19 1/9/12, 3:05 PM10


Antibiotic Dosage GuidelinesG

ENER

AL C

OM

MEN

TS/

Usu

al A

dult

Dos

e1Cr

CLCr

CLCr

CLH

EMO

DIA

LYSI

S2PE

RITO

NEA

LCO

NTI

NU

OU

S RE

NAL

MIC

CO

NSI

DER

ATIO

NS

(CrC

L >5

0 m

L/m

in)

30 to

50

mL/

min

10 to

30

mL/

min

<10

mL/

min

DIA

LYSI

SRE

NAL

REP

LACM

ENT

PEN

ICIL

LIN

S(C

RRT)

4

Amox

icill

in (P

O)

250

to 5

00 m

g q8

h25

0 to

500

mg

q8h

250

to 5

00 m

g q1

2h25

0 to

750

mg

q24h

500

mg

q24h

500

mg

q12h

500

mg

q12h

Amox

icill

in/c

lavu

lana

te (P

O)

875

mg

q12h

875

mg

q12h

500

mg

q12h

500

mg

q24h

500

mg

q24h

250

mg

q12h

500

mg

q12h

Ampi

cilli

n (IV

)1

to 2

g q

4-6h

1 to

2 g

q6-

8h1

to 2

g q

8-12

h1

to 2

g q

12h

1 to

2 g

q12

h50

0 m

g 1

g q1

2h1

to 2

g q

8-12

hCl

oxac

illin

2 g

q4-6

h2

g q4

-6h

Peni

cilli

n G

(IV)

2 to

4 M

Uni

ts q

4h2

M U

nits

q4h

1 M

Uni

ts q

4h1

M U

nits

q4h

1 M

Uni

ts q

4h1

to 2

M U

nits

q4h

Pipe

raci

lln/t

azob

acta

m (I

V)3.

375

g3.

375

g q8

h3.

375

g q8

h3.

375

g q1

2h3.

375

g q1

2h3.

375

g q1

2h3.

375

g q8

h

CEPH

ALO

SPO

RIN

SCe

fazo

lin (I

V)1

g q8

h1

g q8

h1

g q1

2h1

g q2

4h1

g q2

4h50

0 m

g q1

2h1

to 2

g q

12h

Ceph

alex

in (P

O)

500

mg

q6h

500

mg

q6h

500

mg

q8-1

2h50

0 m

g q1

2-24

h50

0 m

g q2

4h50

0 m

g q1

2-24

hN

DCe

furo

xim

e (V

I)75

0 m

g q8

h75

0 m

g q8

h75

0 m

g q1

2h75

0 m

g q2

4h75

0 m

g q2

4h75

0 m

g q1

2h75

0 m

g q1

2hCe

furo

xim

e (P

O)

250

to 5

00 m

g q1

2h25

0 to

500

mg

q12h

250

to 5

00 m

g q2

4h25

0 to

500

mg

q24h

250

to 5

00 m

g q2

4h25

0 to

500

mg

q12h

Ceftr

iaxo

ne (I

V)D

ose

2 g

q12h

for m

enin

gitis

1 g

q24h

1 g

q24h

Cefo

taxi

me

(IV)

Dos

e 1

g q8

h fo

r pne

umon

ia1

to 2

g q

8h1

to 2

g q

8h1

to 2

g q

12h

1 to

2 g

q24

h1

to 2

g q

24h

1 to

2 g

q24

h1

to 2

g q

12h

Dos

e 2

g q4

h fo

r men

ingi

tis2

g q4

h2

g q6

h2

g q8

h2

g q1

2-24

h2

g q1

2-24

h2

g q1

2-24

h2

g q8

hCe

ftazid

ime

(IV)

Dos

e 2

g q8

h fo

r men

ingi

tis1g

IV q

6h1

to 2

g q

12h

1 to

2 g

q24

h1

to 2

g q

48h

1 to

2 g

3x/

wee

k af

ter H

D50

0 m

g q2

4h1

to 2

g q

8hIm

ipen

em (I

V)M

onito

r ren

al fu

nctio

n (S

Cr);

Use

this

dose

em

piric

ally

and

500

mg

q6h

500

mg

q8h

500

mg

q12h

500

mg

q24h

500

mg

q24h

500

mg

q24h

500

mg

q6-8

hw

hen

know

MIC

≤2

mg/

L

QU

INO

LON

ESCi

prof

loxa

cin

(PO

)M

g+2 ,

Ca+2 ,

AI+3 c

onta

inin

g25

0-75

0 m

g q1

2h25

0-75

0 m

g q1

2h25

0-75

0 m

g q2

4h25

0-75

0 m

g q2

4h25

0-50

0 m

g q2

4h25

0-50

0 m

g q2

4h25

0-75

0 m

g q1

2hCi

prof

loxa

cin

(IV)

anta

cids

, iro

n, z

inc,

and

200-

400

mg

q12h

200-

400

mg

q12h

200-

400

mg

q24h

200-

400

mg

q24h

200-

400

mg

q24h

200-

400

mg

q24h

200-

400

mg

q12h

Levo

floxa

cin

(PO

/IV)

sucr

alfa

te ↓

PO

qui

nolo

ne25

0 m

g q2

4h25

0 m

g q2

4h25

0 m

g q4

8h25

0 m

g q4

8h25

0 m

g q4

8h25

0 m

g q2

4hab

sorp

tion

>90%

(sep

arat

e50

0 m

g q2

4h25

0 m

g q2

4h25

0 m

g q4

8h25

0 m

g q4

8h25

0 m

g q4

8h25

0 m

g q2

4had

min

istra

tion

times

≥2

hour

s)75

0 m

g q2

4h75

0 m

g q4

8h50

0 m

g q4

8h50

0 m

g q4

8h50

0 m

g q4

8h50

0 m

g q2

4hM

ACRO

LID

ESAz

ithro

myc

in (I

V)50

0 m

g q2

4h50

0 m

g q2

4hCl

arith

rom

ycin

(PO

)50

0 m

g q1

2h50

0 m

g q1

2h50

0 m

g q2

4h50

0 m

g q2

4h

1-19 1/9/12, 3:05 PM11


Antibiotic Dosage Guidelines (cont’d)G

ENER

AL C

OM

MEN

TS/

Usu

al A

dult

Dos

e1Cr

CLCr

CLCr

CLH

EMO

DIA

LYSI

S2PE

RITO

NEA

LCO

NTI

NU

OU

S RE

NAL

MIC

CO

NSI

DER

ATIO

NS

(CrC

L >5

0 m

L/m

in)

30 to

50

mL/

min

10 to

30

mL/

min

<10

mL/

min

DIA

LYSI

SRE

NAL

REP

LACM

ENT

(CRR

T)4

ANTI

FUN

GAL

S

Amph

oter

icin

B (I

V)0.

5 to

1 m

g/kg

q24

h0.

5 to

1 m

g/kg

q24

h0.

5 to

1 m

g/kg

q24

h(c

onsid

er 5

00 m

L-1

L N

S pr

e- o

r div

ided

pre

- and

post

-infu

sion

to ↓

risk

of n

ephr

otox

icity

)M

icaf

ungi

n10

0 m

g q2

4h10

0 m

g q2

4hLi

pid

amph

oter

icin

BM

onito

r SCr

, K+,

Mg+

+, P

O4;

5 m

g/kg

q24

h5

mg/

kg q

24h

5 m

g/kg

q24

h(IV

) (Ab

elce

t)Ad

min

ister

in D

5W o

ver 2

(con

sider

500

mL-

1 L

NS

pre-

or d

ivid

ed p

re- a

nd p

ost-i

nfus

ion

hour

sto

↓ ri

sk o

f nep

hrot

oxic

ity)

Fluc

onaz

ole

(PO

/IV)

Mon

itor L

FTs;

cons

ider

PO

200

mg

q24h

200

mg

q24h

100

mg

q24h

100

mg

q24h

100

mg

q24h

200

mg

q24h

ther

apy

(>90

% b

ioav

aila

bilit

y);

high

er d

aily

dos

ing

(at l

east

400

mg)

reco

mm

ende

d in

syst

emic

infe

ctio

nsM

onito

r LFT

s; co

nsid

er P

O40

0 to

800

mg

q24h

400

to 8

00 m

g q2

4h20

0 to

400

mg

q24h

200

to 4

00 m

g q2

4h20

0 to

400

mg

q24h

400

to 8

00 m

g q2

4hth

erap

y (>

90%

bio

avai

labi

lity)

;(fo

r sys

tem

ic fu

ngal

high

er d

aily

dos

ing

(at l

east

infe

ctio

ns)

400

mg)

reco

mm

ende

d in

syst

emic

infe

ctio

nsFl

ucyt

osin

e (P

O)

Mon

itor S

Cr, C

BC12

.5 to

25

mg/

kg q

6h12

.5 to

25

mg/

kg q

12-2

4h12

.5 to

25

mg/

kg12

.5 to

25

mg/

kg50

0 m

g to

1 g

12.5

to 2

5 m

g/kg

q24-

48h

q24-

48h

q24-

48h

q24-

48h

Voric

onaz

ole

(IV)3

IV: c

autio

n Cr

CL <

50 m

L/m

in6

mg/

kg q

12h

x 2,

6 m

g/kg

q12

h x

2, th

en 4

mg/

kg q

12h

(cyc

lode

xtrin

may

acc

umul

ate)

then

4 m

g/kg

q12

hPO

dos

e: ≥

40 k

g:20

0 or

300

mg

q12h

, <40

kg:

100

ot 1

50m

g q1

2hCh

ild-P

ugh

Clas

s A o

r B: R

educ

em

aint

enan

ce d

osag

e by

50%

ANTI

VIRA

LS

Acyc

lovi

r (IV

)D

ose

base

d on

idea

l or

5 to

10

mg/

kg q

8h5

to 1

0 m

g/kg

q12

h5

to 1

0 m

g/kg

q24

h2.

5 to

4 m

g/kg

q24

h2.

5 to

5 m

g/kg

q24

h2.

5 to

5 m

g/kg

q24

h5

to 1

0 m

g/kg

q24

had

just

ed b

ody

wei

ght.

Vala

cycl

ovir

(PO

)1

g q8

-12h

1 g

q12h

1 g

q24h

500

mg

q24h

1 g

3x/w

eek

afte

r HD

500

mg

q48h

500

mg

q24h

1-19 1/9/12, 3:05 PM12


Antibiotic Dosage Guidelines (cont’d)G

ENER

AL C

OM

MEN

TS/

Usu

al A

dult

Dos

e1Cr

CLCr

CLCr

CLH

EMO

DIA

LYSI

S2PE

RITO

NEA

LCO

NTI

NU

OU

S RE

NAL

MIC

CO

NSI

DER

ATIO

NS

(CrC

L >5

0 m

L/m

in)

30 to

50

mL/

min

10 to

30

mL/

min

<10

mL/

min

DIA

LYSI

SRE

NAL

REP

LACM

ENT

(CRR

T)4

ANTI

VIRA

LS (c

ont’d

)G

anci

clov

ir (IV

)M

onito

r, W

BC5

mg/

kg q

12h

2.5

mg/

kg q

24h

1.25

mg/

kg q

24h

1.25

mg/

kg 3

x/w

eek

1.25

mg/

kg 3

x/w

eek

1.25

mg/

kg 3

x/w

eek

2.5

mg/

kg q

24h

(indu

ctio

n)af

ter H

D5

mg/

kg q

24h

1.25

mg/

kg q

24h

0.62

5 m

g/kg

q24

h0.

625

mg/

kg 3

x/w

eek

0.62

5 m

g/kg

3x/

wee

k0.

625

mg/

kg 3

x/w

eek

1.25

mg/

kg q

24h

(mai

nten

ance

)af

ter H

DVa

lgan

cicl

ovir

(PO

)90

0 m

g q1

2h45

0 m

g q1

2h45

0 m

g q4

8h

ID

or T

rans

plan

t con

sult

(indu

ctio

n)(C

rCL

40-5

9)45

0 m

g q4

8h (C

rCL

25-3

9)90

0 m

g q2

4h45

0 m

g q2

4h45

0 m

g tw

ice

wee

kly

ID o

r Tra

nspl

ant c

onsu

lt(m

aint

enan

ce)

(CrC

L 40

-59)

450

mg

q48h

(CrC

L 25

-39)

ANTI

TUBE

RCU

LOSI

SEt

ham

buto

l (PO

)M

onito

r uric

aci

d,15

to 2

5 m

g/kg

q24

h15

to 2

5 m

g/kg

q24

-36h

15 to

25

mg/

kg q

48h

15 to

25

mg/

kg q

48h

15 to

25

mg/

kg q

48h

15 to

25

mg/

kg q

24-3

6hLF

Ts; v

ision

test

Isoni

azid

(PO

)M

onito

r LFT

s5

mg/

kg q

24h

5 m

g/kg

q24

hPy

razin

amid

e (P

O)

Mon

itor L

FTs

15 to

30

mg/

kg q

24h

15 to

30

mg/

kg q

24h

15 to

30

mg/

kg q

24h

Rifa

mpi

n (IV

, PO

)3M

onito

r LFT

s; sig

nific

ant

600

mg

q24h

600

mg

q24h

drug

inte

ract

ion

pote

ntia

l

MIS

CELL

ANEO

US

Clin

dam

ycin

(IV)

360

0 to

900

mg

q8h

600

to 9

00 m

g q8

hD

apto

myc

in (I

V)M

onito

r bas

elin

e an

d6

to 8

mg/

kg q

24h

6 to

8 m

g/kg

q24

h6

to 8

mg/

kg q

48h

6 to

8 m

g/kg

pos

t HD

6 to

8 m

g/kg

q48

h6

to 8

mg/

kg q

24h

wee

kly

CPK

leve

lsD

oxyc

yclin

e (IV

, PO

)10

0 m

g q1

2h10

0 m

g q1

2hLi

nezo

lid (I

V, P

O)

Mon

itor C

BC: c

onsid

er60

0 m

g q1

2h60

0 m

g q1

2hPO

ther

apy

(-100

% b

ioav

aila

bilit

y)M

etro

nida

zole

(IV,

PO

)350

0 m

g q8

-12h

500

mg

q8-1

2h50

0 m

g q1

2h50

0 m

g q8

-12h

1-19 1/9/12, 3:05 PM13


Antibiotic Dosage GuidelinesG

ENER

AL C

OM

MEN

TS/

Usu

al A

dult

Dos

e1Cr

CLCr

CLCr

CLH

EMO

DIA

LYSI

S2PE

RITO

NEA

LCO

NTI

NU

OU

S RE

NAL

MIC

CO

NSI

DER

ATIO

NS

(CrC

L >5

0 m

L/m

in)

30 to

50

mL/

min

10 to

30

mL/

min

<10

mL/

min

DIA

LYSI

SRE

NAL

REP

LACM

ENT

(CRR

T)4

MIS

CELL

ANEO

US

(con

t’d)

Colis

tin (I

V)Re

duce

dos

e w

hen

CrCL

2.5-

3 m

g/kg

q24

h2.

5 to

3 m

g/kg

load

2.5

to 3

mg/

kg lo

ad x

1,

2.5

to 3

mg/

kg lo

ad x

1, t

hen

1 m

g/kg

q3-

5 da

ys<8

0 m

L/m

in; m

onito

r SCr

,(c

an d

ivid

e do

se 1

2h)

x 1,

then

1 to

1.5

then

1 to

1.5

mg/

kg q

2-3

days

elec

troly

tes,

neur

oact

ivity

mg/

kg q

24h

Tige

cycl

ine

(IV)3

Seve

re (C

hild

-Pug

h Cl

ass C

)10

0 m

g x

1, th

en 5

010

0 m

g x

1, th

en 5

0 m

g q1

2hhe

patic

impa

irmen

t: 10

0 m

gm

g q1

2hx

1, th

en 2

5 m

g q1

2hTr

imet

hopr

im/s

ulfa

(IV,

PO

)M

onito

r SCr

, WBC

, pla

tele

t2.

5 to

5 m

g/kg

q6-

12h

2.5

to 5

mg/

kg2.

5 to

5 m

g/kg

2.5

to 5

mg/

kg q

24h

2.5

to 5

mg/

kg q

24h

coun

tq6

-12h

(TM

P)q6

-12h

q12

-24h

1 The

dos

ing

reco

mm

enda

tions

pre

sent

ed h

ere

are

for -

70 k

g ad

ults

with

mod

erat

e to

seve

re in

fect

ions

bas

ed o

n pu

blish

ed li

tera

ture

and

clin

ical

exp

erie

nce.

The

se re

com

men

datio

ns sh

ould

onl

y be

use

d as

gui

delin

es a

nd d

osin

g ba

sed

on p

harm

acok

inet

ic a

nd c

linic

al e

valu

atio

n is

sugg

este

d w

here

pos

sible

. 2 For

ant

imic

robi

als d

osed

eve

ry 2

4 ho

urs i

n pa

tient

s on

hem

odia

lysis

, dos

es sh

ould

be

adm

inist

ered

afte

r dia

lysis

on

dial

ysis

days

. Alte

rnat

ivel

y, a

ll do

ses m

ay b

ead

min

ister

ed o

nce

daily

in th

e ev

enin

g to

ens

ure

adm

inist

ratio

n af

ter d

ialy

sis o

n di

alys

is da

ys. 3 D

osin

g ad

just

men

t may

be

nece

ssar

y in

pat

ient

s with

seve

re li

ver d

ysfu

nctio

n. 4 F

or p

atie

nts r

ecei

ving

con

tinuo

us v

eno-

veno

ushe

mof

iltra

tion

(CVV

H) o

r con

tinuo

us v

eno-

veno

us h

emod

iafil

tratio

n (C

VVH

DF)

at ≥

1 L

/h; N

D =

no

data

ava

ilabl

e.

1-19 1/9/12, 3:05 PM14


Antibiotic Dosing in ObesityObesity can be defined based on the percentage above idealbody weight (% IBW) or based on the body mass index (seeTable I). Although several equations have been formulated,the Devine formulas (see Equations 1 and 2) are mostfrequently used to calculate IBW.

Table I: Defining Obesity

Classification % IBW Body Mass Index (BMI)

Normal 80 -125% IBW 18.5 -24.9 kg/m2

Obese 126 -190% IBW 30.0 -39.9 kg/m2

Morbidly obese >190% IBW >40 kg/m2

Equation 1: IBW(male) = 50 kg + 2.3 kg x (inches over 5ft tall)

Equation 2: IBW(female) = 45.5 kg + 2.3 kg x (inches over 5ft tall)

Since obesity can impact the distribution and clearance ofdrugs, changes to the volume of distribution (Vd) and totalbody clearance (CL) are the key pharmacokinetic parametersthat must be considered in calculating the dose of antibioticnecessary to achieve desired serum concentrations. The Vd isphysiologically determined by the volume of blood, thevolume of body tissues and organs, and the binding of thedrug in the tissues relative to the blood. The Vd in obesepatients, therefore, depends on the drug’s affinity for andquantity of adipose tissue; a greater affinity for adipose tissueaffords a greater volume for drug accumulation. In additionto physiologic determinants, the Vd of antibiotics can beinfluenced by the drug’s solubility in body water relative toadipose tissue. Most antibiotics are hydrophilic and willdistribute into body water better than into adipose tissue(e.g., acyclovir). For these antibiotics, Vd correlates betterwith lean body mass, or IBW. However, since lean body masstends to increase along with adipose tissue in obesity, the Vdfor some hydrophilic drugs (e.g., aminoglycosides) correlatesbetter with adjusted body weight (ABW). On the other hand,lipophilic compounds (e.g., amphotericin B), may have an

1-19 1/9/12, 3:05 PM15


Antibiotic Dosing in Obesity (cont’d)expanded Vd in obese patients, and thus correlate betterwith total body weight (TBW). Finally, it should be noted thatTBW is also recommended as the basis for dosing certainobese patient populations with hydrophilic antibiotics when(a) the safety of this approach has been demonstrated (e.g.,daptomycin), or when (b) clinically significant differences inVd and CL have not been detected in comparative studies(e.g., dalfopristin-quinupristin).

Calculating the Vd (see Equation 3) can help to determine anappropriate loading dose for obese patients. For thiscalculation, the Vd determined for a drug in a non-obesepopulation is simply multiplied by a factor that takes intoaccount the excess body weight and corrects for additionaldistribution of the drug into adipose tissue. A genericcorrection factor of 0.4 for hydrophilic drugs is an average offactors (0.37-0.58) validated in pharmacokinetic studies ofaminoglycosides, but different correction factors arerecommended for beta-lactams (0.3) and ciprofloxacin(0.45). Although the generic correction factor of 0.4 isinferred from theoretical data on aminoglycosides, it providesthe best current alternative for estimating the parameter forother hydrophilic antibiotics when clinical studies in obesepatients are lacking.

Equation 3: Vd(obese) = Vd(non-obese) x Adjusted Body Weight

Adjusted Body Weight = IBW + [(*C) x (TBW - IBW)]

*C = correction factor (see explanation in text above andTable III below)

1-19 1/9/12, 3:05 PM16


Antibiotic Dosing in ObesityLiterature-Based Antibacterial Dosing Recommendations for Obese Patients

Antibacterial Primary Considerations Adult, non-obese, Recommendation(s) Agent normal renal function

Vd (L/kg) t1/2 (h)

-Initial doses should be based on Vdusing ABW with correction factor of0.4 (ABW=IBW+0.4[TBW-IBW]).-Final dosage adjustments should bebased on serum concentrations.

-No dose adjustmentrecommended.

-Increase non-obese dose of 2 g IVq4h to 3 g IV q6h in obeseindividuals.-No dose adjustmentrecommended.-Base dose on diagnosis and CLcr.

-Base dose on CLcr.

-Use 2 g for surgical prophylaxis. -Pories et al. suggest 1 g IV, 2hbefore surgery and at induction ofanesthesia, followed by 500 mg IVq6h x 8 doses.

-No information on obesity dosingavailable.Base dose on Vd using ABW withcorrection factor for H20composition of adipose tissue(ABW=IBW + 0.3 [TBW-IBW]).-Base dose on Vd using ABW withcorrection factor for H20composition of adipose tissue(ABW=IBW + 0.3 [TBW-IBW]).-Base dose on CLcr.-No information on obesity dosingavailable. Base dose on Vd usingABW with correction factor for H20composition of adipose tissue(ABW=IBW + 0.3 [TBW-IBW]).-Base dose on CLcr.

0.26 2

0.25 1.5-4

0.26 1.6-3

0.27-0.29 1-1.9

0.57-1.55 0.5-1

0.47 0.3-0.8

0.14-0.23 0.9

T:0.15 T: 1C: 0.29 C: 1-1.5

0.13-0.22 1.5-2.5

0.2-0.29 2

0.46-0.53 0.8-1.4

0.28-9.4 1.6-20.08-0.19 5.8-8.7

0.17-0.31 1.1-1.9

AminoglycosidesAmikacin

Gentamicin

Tobramycin

βββββ-Lactams/PenicillinsAmpicillin

Cloxacillin

Penicillin G

Piperacillin-Tazobactam*

Ticarcillin-Clavulanate*βββββ-Lactams/CephalosporinsCefazolin

Cefepime*

Cefotaxime

Ceftazidime*Ceftriaxone*

Cefuroxime*

-Aminoglycosides are primarilydistributed into extracellularfluids (ECF).-Higher CL, but greater Vdcancels out effect; alteration indosage interval not necessary.

-Distributed in adipose tissue tosome extent, but serumconcentration not reported.-Significant increase in Vd(almost double that ofnon-obese parameter).-Drug absorption and serumlevels not altered by obesity.-Not evaluated in obese patients;multi-center trials studiedpatients with mean TBW of 73.3kg.-CL and Vd not affected bychanges in TBW.-No data available.

-In surgical prophylaxis, lowermean serum and adipose tissueconcentrations in obese patients.-Higher prophylactic dosesneeded to achieve serum andtissue concentrations similar tothose in non-obese patients.-Hydrophilic drug.-No data available.

-Hydrophilic drug, Vd and CLincreased 50% and 25%,respectively in patients rangingfrom 190% to 210% of IBW.-No data available.-No data available.

-No data available.

In addition to Vd, alterations in total body clearance (CL) should also be considered in determining amaintenance dose and dosing interval necessary to achieve desired steady-state concentrations in obesepatients. The Cockcroft and Gault equation is most commonly used in clinical practice to estimate drugclearance, but the accuracy of this method is limited to normal-weight patients. Although obesity generallyis associated with an increase in creatinine clearance (CLcr), the original Cockcroft and Gault equationtends to overestimate the parameter, prompting several modifications to the original.

1-19 1/9/12, 3:05 PM17


Antibiotic Dosing in Obesity (cont’d)Literature-Based Antibacterial Dosing Recommendations for Obese Patients


Vd (L/kg) t1/2 (h)βββββ-Lactams/CarbapenemsErtapenem

Meropenem

Imipenem-Cilastatin*

FluoroquinolonesCiprofloxacin

Levofloxacin*

Moxifloxacin*

MacrolidesAzithromycin*

Erythromycin

MiscellaneousAcyclovir

Amphotericin B

Aztreonam*

Clindamycin*

Daptomycin

-AUC was significantly decreasedin obese and morbidly obesepatients; however, no dosingadjustment was recommended.-Increased CL, Vd, and t1/2.-Percentage of time the dose wasabove the MIC during an 8hdosing interval was notsignificantly different.-No data available.

-Less distributed to adipose tissue,Vd increased by 23%, increasedCL, and lower C max; however,concentrations still withinrecommended therapeutic range.-Drug is lipophilic, and widelydistributed into body tissues.

-No data available.

-Peak concentrations similar inobese and non-obese adults.

-Pharmacokinetics notsignificantly different in obeseand non-obese groups.-Half-life depends on renalfunction.-Drug is lipophilic.-Zucker rats withhyperlipoproteinemia: ↓Vd, ↓CL,↑renal toxicity.-Drug is lipophilic.

-No data available.

-Increased Vd and CL in obese vs.non-obese subjects.-Large molecular mass with highpolarity, low lipid solubility, andhigh plasma protein binding.-Exposure increased by 25-30%when dose based on TBW, butstill safe and tolerated in subjectsranging from 56-147 kg.

-Use standard dose of 1 g/day.

-No dose adjustmentrecommended.

-Base dose on CLcr.

-Dose should be based on Vd usingABW with correction factor of 0.45(ABW = IBW + 0.45[TBW-IBW]).

-No information on obesity dosingavailable. Data suggest obesitymay not alter PK.-Base dose on CLcr.-Use standard dose of 400 mgIV/PO daily.

-No information on obesity dosingavailable.-Base dose on IBW.

-Base dose on IBW.

-Use traditional dosing of 0.5-1.5mg/kg based on TBW.

-Use dose at upper end of range fortreating serious infections inmorbidly obese adults.

-No information on obesity dosingavailable.-Base dose on TBW.

0.11 4

0.33-0.43 1

0.14-0.33 1

1.2-2.7 3-6

1.25 6-8

1.7-2.7 14.8

2 3 - 3 1 1 1 - 6 8

0.57 1-1.5

0.8 2 .2 -20

4 360

0.1-0.2 1.5-3

0.6-1.2 1 .5 -5

0.12 7 - 1 1

1-19 1/9/12, 3:05 PM18


Antibiotic Dosing in Obesity (cont’d)Literature-Based Antibacterial Dosing Recommendations for Obese Patients


Vd (L/kg) t1/2 (h)Miscellaneous (cont’d)Doxycycline*

Fluconazole

Linezolid

Metronidazole*

Sulfamethoxazole-Trimethoprim*Tigecycline*

Vancomycin

Voriconazole (oral)

Drug is lipophilic.

-Hydrophilic agent, eliminatedby kidney.

-Prolonged inhibitory activityobserved despite ↓ serumconcentrations.-No data available.

-No data available.

-Study subjects weighed 39-200kg.-Increased Vd and CL in obesepatients correlates better withTBW.

-Vd and CL same in obese andnon-obese.

-No information on obesitydosing available.-A higher dose is recommended(e.g., 1200 mg/day for candidafungaemia).-Use standard dose of 600 mgIV/PO q12h.

-No information on obesitydosing available.-No information on obesitydosing available.-Use traditional dose of 100 mgIV followed by 50 mg IV q12h.-Base dose on TBW, giving 20-30mg/kg/day.-If necessary, shortenadministration interval tomaintain serum trough >5 mg/L.-Adjustment of oral Voriconazolein patients with Class II obesity isnot necessary on the basis of TBW.

0.75 15-24

0.56-0.82 30

0.57-0.86 5

0.25-0.85 6-14

S: 0.360 S: 8-11T: 2 T: 6-177-9 42

0.7 7-9

1-19 1/9/12, 3:05 PM19


Automatic Therapeutic Interchange

See Sequential Antibiotic Therapy (SAT) for information on “pharmacist initiated route of administration”therapeutic interchange.

Preparation/regimen ordered Dispensed asAmpicillin Amoxicillin•250 mg po q6h •250 mg q8h•500 mg po q6h •500 mg q8h•1000 mg po q6h •500 mg q8hCeFAZolin ___ mg IV q6h CeFAZolin ___ mg IV q8hCeFAZolin 500 mg po q6h Cephalexin 500 mg po q6hCefoxitin CeFAZolin•1 g IV q6-8h •1 g IV q8h and metronidazole 500 mg IV q8h•2 g IV q6-8h •2 g IV q8h and metronidazole 500 mg IV q8hCefUROXime 1 g IV CefUROXime 750 mg IVCephalothin ___ mg IV q6h CeFAZolin ___ mg IV q8hCiprofloxacin 500 mg inj Ciprofloxacin 400 mg injCiprofloxacin 400 mg tab Ciprofloxacin 500 mg tabClindamycin ___ mg IV q6h Clindamycin ___ mg IV q8h [total daily dosage

no more than 1800 mg (Exception: gynecologypatients being treated for PID and necrotizingfasciitis may receive 900 mg IV q8h)]

Erythromycin IV (all regimens) Azithromycin 500 mg IV dailyErythromycins, oral•Ethylsuccinate/lactobionate •Erythromycin base•Estolate •Erythromycin stearate•Erythromycin base •Erythromycin base(enteric/particle-coated tab) (conventional-release; equivalent regimen)Gatifloxacin 400 mg IV/po days 1 & 2, then Levofloxacin 500 mg IV/po day 1, then 250 mgq48h thereafter q24h thereafterMeropenam ___ mg IV q__h Imipenem ___ mg IV q__hItraconazole cap Itraconazole sol (equivalent regimen)Metronidazole ___ mg IV q6-8h Metronidazole ___ mg IV q12 h

(Exception: cefoxitin interchange q8h)Metronidazole 250 mg IV q12h Metronidazole 500 mg IV q12hNitrofurantoin, macrocrystalline formulation Nitrofurantoin, conventional formulationMacrodantinNitrofurantoin, sustained release Nitrofurantoin, conventional-release (equivalentMacrobid regimen)Penicillins•Penicillin G 500 000 IU (300 mg), oral •Penicillin V potassium 300 mg, oral•Penicillin G inj •Penicillin G sodium inj•Penicillin G potassium inj •Penicillin G sodium inj•Penicillin V potassium 250 mg (400,000 IU) •Penicillin V potassium 300 mg (500,000 IU)•Penicillin V potassium 500 mg •Penicillin V potassium 600 mg•Penicillin V 300 mg •Penicillin V potassium 300 mgVancomycin IV inj q __ h All dosing intervals less than q12h changed to

q12h with total daily dosage remaining thesame (e.g. 500 mg q6h becomes 1 g q12h)

Vancomycin cap Vancomycin inj (to be reconstituted andadministered orally at the prescribed dosage)

20-31 1/10/12, 10:16 AM20

UPDATED

May 20

19


Quinolone and Enteral Nutrition PolicyD

o no

t ad

min

iste

r N

G Q

uino

lone

s in

cri

tica

lly

ill*

pat

ient

s re

ceiv

ing

Ent

eral

Fee

ds

Sum

mar

y of

Ava

ilabl

e Dat

a Ev

alua

ting

the C

ompa

tibili

ty o

f Cip

roflo

xacin

Coa

dmin

ister

ed w

ith E

nter

al N

utrit

ion

Pre

pare

d by

: Ta

sha

Mui

se, K

athr

yn S

layt

er, T

here

sa H

urle

y, H

oan

Lin

h B

anh

Aug

ust,

200

1

Stud

y

Wrig

ht D

, Piet

z S, K

onsta

ntin

ides

K. e

t al.

Dec

reas

ed In

Vitr

o Fl

uoro

quin

olon

e Co

ncen

trat

ions

Afte

rAd

mix

ture

With

an

Ente

ral F

eedi

ng F

orm

ulat

ion.

JPEN

200

0;24

(1):4

2-48

De M

arie

S, V

ande

nber

gh M

, Bui

jk S

et a

l.Bi

oava

ilabi

lity

of c

ipro

floxa

cin a

fter m

ultip

le e

nter

alan

d in

trav

enou

s dos

es in

ICU

patie

nts w

ith se

vere

gram

neg

ativ

e in

tra-

abdo

min

al in

fect

ions

. Int

ensiv

eCa

re M

ed 1

998;

24:

343-

6

Mim

oz O

, Bin

ter V

, Jac

olot

A e

t al.

Phar

mac

okin

etics

and

abs

olut

e bi

oava

ilabi

lity

ofcip

roflo

xacin

adm

inist

ered

thro

ugh

a na

soga

stric

tube

with

con

tinuo

us e

nter

al fe

edin

g to

crit

ically

ill

patie

nts.

Inte

nsive

Car

e M

ed 1

998;

24:

1047

-51

Healy

D, B

rodb

eck

M, C

lende

ning

C. C

ipro

floxa

cinAb

sorp

tion

is Im

paire

d in

Pat

ient

s Giv

en E

nter

alFe

edin

gs O

rally

and

via

Gas

tros

tom

y an

dJe

juno

stom

y Tu

bes.

Antim

icrob

Age

nts C

hem

othe

r19

96;4

0(1)

:6-1

0

Cohn

S, S

awye

r M, B

urns

G e

t al.

Ente

ric a

bsor

ptio

nof

Cip

roflo

xacin

dur

ing

tube

feed

ing

in th

e cr

itica

llyill

. J A

ntim

icrob

Che

mo

1996

;38:

871-

876

Mue

ller B

, Brie

rton

D, A

bel S

et a

l. Ef

fect

of E

nter

alFe

edin

g w

ith E

nsur

e on

Ora

l Bio

avai

labi

litie

s of

Oflo

xacin

and

Cip

roflo

xacin

. Ant

imicr

ob A

gent

sCh

emot

her.

1994

;38(

9):2

101-

5

Yuk

J, N

ight

inga

le C,

Sw

eene

y K

et a

l. Re

lativ

eBi

oava

ilabi

lty in

Hea

lthy

Volu

ntee

rs o

f Cip

roflo

xacin

Adm

inist

ered

thro

ugh

a N

asog

astr

ic Tu

be w

ith a

ndw

ithou

t Ent

eral

Fee

ding

. Ant

imicr

ob A

gent

s

Patie

nt P

opul

atio

n (#

pat

ient

s)

N/A

Criti

cally

ill i

nten

sive

care

pat

ients

with

GNIA

I(n

=5)

Stab

le cr

itica

lly il

lpa

tient

s (n=

12)

Stab

le ho

spita

lized

patie

nts (

n=26

)

Mec

hani

cally

ven

tilat

edpa

tient

s with

pneu

mon

ia(n

=7)

Healt

hy v

olun

teer

s(n

=13)

Healt

hy m

ale

Stud

y D

esig

n an

d Tr

eatm

ent

Cipr

o 50

0mg

tabl

et c

rush

ed a

nd a

dded

to 2

40m

L of

eac

h of

the

follo

win

g;W

ater

Wat

er +

calc

ium

Wat

er +

mag

nesiu

mW

ater

+ c

alciu

m +

mag

nesiu

mEn

sure

Rand

omize

d, tw

o se

quen

ce c

ross

over

stud

y;(a

)cip

ro 4

00 m

g IV

q12

h(b

)cip

ro 7

50 m

g ta

bs d

issol

ved

in sa

line

solu

tion,

add

ed to

ent

eral

feed

ing

and

deliv

ered

via N

G or

nas

oduo

dena

l tub

e 12

h

Pros

pect

ive, c

ross

over

stud

y;(a

)cip

ro 1

00 m

g IV

(1hr

infu

sion)

(b)c

ipro

750

mg

tab

crus

hed

+ w

ater

Rand

omize

d cr

osso

ver s

tudy

1.O

ral T

reat

men

t Gr o

up(a

)cip

ro 5

00 m

g(b

)cip

ro 5

00 m

g +

Susta

cal 2

40 m

L2.

G tu

be o

r J tu

be T

reat

men

t Gr o

up(c

)cip

ro 5

00 m

g cr

ushe

d in

60

mL

wat

er v

iafe

edin

g tu

be(d

)cip

ro 5

00 m

g +

Jevit

y

Subj

ects

rece

ived

cipro

floxa

cin 7

5 m

g q1

2h v

iaN

G tu

be a

nd se

rial d

rug

conc

entra

tions

wer

em

easu

red

afte

r the

1st a

nd 4

th d

ose.

Rand

omize

d cr

osso

ver d

esig

n w

ith 4

trea

tmen

ts;

(a)o

floxa

cin +

120

mL

wat

er(b

)oflo

xacin

400

mg+

120

mL

Ens

ure

(c)c

ipro

750

mg

+ 12

0 m

L w

ater

(d)c

ipro

750

mg

+ 12

0 m

L En

sure

Rand

omize

d, th

ree

way

cro

ssov

er st

udy;

(a)c

ipro

750

mg

tab

po(b

)cru

shed

750

mg

cipro

tab

susp

ende

d in

50

mL

of w

ater

adm

inist

ered

thro

ugh

an N

G tu

be(c

)cru

shed

750

mg

cipro

tab

susp

ensio

nad

min

ister

ed th

roug

h an

NG

tube

+ O

smol

ite

Ente

ral P

rodu

ct(c

onte

nts m

g/10

0 m

L)

Ensu

reCa

53.

75 m

gM

g 20

.9 m

gFe

2.2

5 m

gZn

2.8

2 m

gCo

0.2

5 m

g

Nut

rison

Ca 5

0 m

gM

g 20

mg

Fe 1

mg

Zn 1

mg

Nor

mo-

Real

Fibre

sCa

60

mg

Mg.

20 m

gFe

0.8

mg

Jevit

y

Susta

cal

Ca 1

37 m

g Ca

104

mg

Mg

46 m

g M

g 41

.6 m

gFe

2.1

mg

Fe 0

.2 m

gZn

2.6

mg

Zn

0.02

mg

Co 2

.3 m

g C

o 0.

38 m

g

Pulm

ocar

eCa

104

mg

Mg

62 m

gFe

2 m

gZn

2.4

mg

Co 2

.2 m

g

Ensu

reCa

53.

75 m

gM

g 20

.9 m

gFe

2.2

5 m

gZn

2.8

2 m

gCo

0.2

5 m

g

Osm

olite

Ca 5

3 m

gM

g 22

mg

Fe 0

.9 m

gZn

1.2

mg

Co 0

.11

mg

Cmax

(ug/

mL)

N/A

a)6.

8 (3

.9-9

.8)

b)3.

2 (1

.8-4

.6)

a)4.

1 (1

.5-7

.4)

b)2.

3 (0

.7-5

.8)

oral

1.43

±0.6

1g-

tube

2.27

±0.6

7j-t

ube1

.45±

0.48

Dose

1:

2.29

(1.2

4-3.

06)

Dose

4:

2.23

(1.2

0-3.

76)

c)3.

79±0

.72

d)1.

99±0

.57

a)2.

80±0

.94

b)2.

12±0

.37

AUC

0_∞

(ug.

h/m

L)

N/A

a)19

.3 (1

1.8-

26.7

)b)

19.1

(1.8

-27.

5)

a)10

.3 (3

.3-3

4.6

b)8.

4 (3

.6-5

3.4)

oral

9.44

±4.7

4g-

tube

7.4

4±3.

16j-t

ube

5.82

±2.6

3

Dose

1:

9.90

(3.2

0-19

.65)

Dose

4:

10.6

3 (4

.32-

19.2

6)

c)15

.96±

3.12

d)11

.66±

3.70

a)13

.17±

4.81

b)11

.46±

4.51

Bioa

vaila

bilit

y(%

)

N/A

a)N

/Ab)

53.1

(43.

5-62

.8)

44 (3

1-82

)

27 -

67

N/A

c)N

/Ad)

72±1

4

Mea

n Ph

arm

acok

inet

ic Pa

ram

eter

sSt

udy

Con

clusio

n

Ther

e is

an im

med

iate,

and

sign

ifica

nt lo

ss o

f FQ

whe

n m

ixed

with

Ens

ure

(ave

rage

dec

reas

e of

82.

5±1.

5% fo

r cip

roflo

xacin

and

61.

3% ±

5.2

% fo

rlev

oflo

xacin

500

mg

tab)

. An

expl

anat

ion

for t

he lo

ssre

main

s unc

lear.

Adeq

uate

spac

ing

of E

nsur

ead

min

istra

tion

(at l

east

2 h

befo

re a

nd a

fter F

Qdo

sing)

is re

com

men

ded.

Ente

ral d

osin

g of

cip

roflo

xacin

750

mg

bid

resu

lted

inad

equa

te se

rum

leve

ls in

tube

-fed

ICU

patie

nts w

ithse

vere

GN

IAI,

and

can

ther

efor

e be

use

d in

the

treat

men

t of s

uch

patie

nts.

In tu

be-fe

d cr

itica

lly il

l pat

ients,

a sw

itch

to N

Gcip

roflo

xacin

afte

r ini

tial t

hera

py to

sim

plify

the

treat

men

t of s

ever

e in

fect

ions

, is r

estri

cted

to th

ose

who

m se

rial a

sses

smen

ts of

cip

roflo

xacin

leve

ls ar

ero

utin

ely a

vaila

ble.

Decr

ease

d ab

sorp

tion

of c

ipro

floxa

cin m

ay b

e of

clini

cal i

mpo

rtanc

e w

hen

the

ente

ral f

eedi

ng is

coad

min

ister

ed w

ith c

ipro

by

the

oral

or jt

ube

rout

es. R

educ

tions

in m

ax le

vels

of c

ipro

in se

rum

, as

a re

sult

of fe

edin

gs g

iven

via g

tube

, are

sim

ilar t

oth

ose

follo

win

g or

al ad

min

istra

tion

on a

n em

pty

stom

ach,

mak

ing

a cli

nica

lly im

porta

nt in

tera

ctio

n by

this

rout

e les

s like

ly.

GI a

bsor

ptio

n of

cip

roflo

xacin

in tu

be fe

d cr

itica

lly il

lpa

tient

s was

dec

reas

ed, b

ut w

ell a

bove

MIC

valu

esfo

r man

y pa

thog

enic

bact

eria.

Switc

hing

from

par

ente

ral a

ntib

iotic

s to

oral

cipro

floxa

cin in

a p

atien

t rec

eivin

g En

sure

cou

ldre

sult

in u

ndes

irabl

y lo

w c

once

ntra

tions

in se

rum

.

Cipr

oflo

xacin

is w

ell a

bsor

bed

afte

r adm

inist

ratio

n via

NG

tube

(com

pare

d w

ith a

n or

ally

adm

inist

ered

inta

ct ta

blet

) eve

n in

the

pres

ence

of e

nter

al fe

edin

g.Th

us, e

nter

al fe

edin

g do

es n

ot h

ave

to b

e in

terru

pted

whe

n ad

min

sterin

g cip

roflo

xacin

.

* Con

com

itant

use

in a

ll ot

her p

atie

nts

at c

linic

al d

iscr

etio

n. If

use

d, s

pace

qui

nolo

ne a

nd fe

eds

by 2

-4 h

ours

.

20-31 1/10/12, 10:16 AM21


Aminoglycoside Antibiotics – Dosingand Monitoring Guidelines

In spite of recent advances made with the introduction of extended spectrum beta-lactamantibiotics, the aminoglycosides remain a major class of antibiotics for the treatment ofserious Gram negative infections.

1. SPECIFIC AMINOGLYCOSIDES

• Gentamicin

• Tobramycin

• Amikacin

2. ADVERSE EFFECTS

Associated toxicities are primarily those of ototoxicity (evidenced by sometimesirreversible hearing loss in the high and low frequency range, nausea, tinnitus and vertigo)and nephrotoxicity (generally reversible acute tubular necrosis signalled by elevations inserum creatinine). Several factors contribute to the risk of aminoglycoside toxicity.

• Length of therapy > 10 days• Renal insufficiency• Elevated aminoglycoside trough serum concentrations• Concomitant nephrotoxic and ototoxic drugs• Recent prior exposure to nephrotoxic medications

(e.g. aminoglycosides, amphotericin B, cyclosporine, etc.)• Pre-existing cochlear/vestibular dysfunction• Sodium/volume depletion• Old age• Renal transplants

3. MONITORING

Certain baseline monitoring parameters should be obtained and followed at therecommended time intervals whenever possible.

Baseline Parameter Follow-up

Weight, height Weekly as appropriate

Blood urea nitrogen Twice weekly

Serum creatinine Twice weekly (Unstable renal function) (Daily)

Intake and output As required

Clinical and laboratoryparameters of infection As appropriate (WBC, temperature)

20-31 1/10/12, 10:16 AM22


In addition, audiograms are recommended for patients at risk.• Patients with pre-existing hearing disorders.• Concurrent ototoxic drugs (e.g. cisplatin).• Prior exposure to a therapeutic course of an aminoglycoside (within 3 months).• Aminoglycoside therapy anticipated to exceed 14 days.

Monitoring of serum aminoglycoside concentrations is discussed within the dosing guide-lines.

4. ONCE-DAILY DOSING GUIDELINES

RECOMMENDATIONUpon the advice of the Antimicrobial Agents Sub- Committee and the District Drugs andTherapeutics Committee, patients receiving aminoglycoside therapy may be prescribed aonce-daily dosing schedule. Please see Table 1 for appropriate dosing interval for patientswith a CLcr between 20 and 59 mL/min.

a) PATIENT EXCLUSION:• Dialysis • Ascites• Renal failure (CLcr < 20 mL/min) • Burns (> 20%)• Single prophylactic dose before an • Low level synergy in which peaks of

operative or diagnostic procedure 3-5 mg/L are required and morefrequent dosing preferred(i.e. enterococcus, staph, endocarditis)

b) DOSAGE• Determine dosing weight:

For non-obese patients their actual body weight (ABW) is the dosing weight

For obese patients (i.e. 20% above ideal body weight (IBW)), calculate dosing weight asfollows: Obese dosing weight = IBW + 0.4 (ABW - IBW)

• The recommended dose of gentamicin or tobramycin is 6 mg/kg and 15 mg/kg foramikacin in 100 mL of a compatible intravenous solution infused over 1 hour.

c) DOSING INTERVALDetermine the patient’s creatinine clearance (CLcr) and choose the corresponding dosinginterval from Table 1.

Table 1. Dosing Interval

Creatinine Clearance (mL/min) Dosing Interval

> 60 q24h

40-59 q36h

20-39 q48h

< 20 Avoid once daily dosing

Aminoglycoside Antibiotics – Dosingand Monitoring Guidelines (cont’d)

20-31 1/10/12, 10:16 AM23



d) SERUM DRUG MONITORINGStandard peak and trough concentrations are not necessary. However, some patientsshould receive a level (6 hours before the end of the dosing interval) to be obtained on the1st dose and every 4 days thereafter; to assess for adequate clearance. The level forgentamicin/tobramycin should be <1 mg/L and amikacin <2.5 mg/L. Levels should beroutinely monitored in the following:

• patients with CLcr between 40-59 mL/min (i.e. q36h)• patients with CLcr between 20-39 mL/min (i.e. q48h)• patients in the ICU• aminoglycoside therapy > 5 days• CLcr decrease from baseline > 25%• infections involving highly resistant organisms• patients on concurrent nephrotoxins• patients > 65 years of age

Levels need not be obtained for patients with all of the following criteria:

• < 65 years old• CLcr > 60 mL/min• not receiving concurrent nephrotoxins• not receiving renal contrast media

CYSTIC FIBROSIS PATIENTS

Tobramycin DosingDose according to estimated CrClCrCl >50 mL/min = 10 mg/kg/24 hCrCl 30-49 mL/min = 10 mg/kg/36 hCrCl 20-29 mL/min = 10 mg/kg/48 hCrCl <20 mL/min, ARF = 3 mg/kg x 1 CONSULT PHARMACY

LabsAt the time of writing for Once Daily Dosing, please order:Pre level (6 hours before next dose)

Dosage IncreasesIf pre level (drawn 6 hours before the next dose) is undetectable, consider increasing thetobramycin dosage to 12.5 mg/kg/day.Repeat 6 hours pre level on new dosage.

Maximum Tobramycin DosageMaximum dosage is 15 mg/kg/dayWhen using this dosage >10 mg/kg/day, order peak levels 90 minutes after the end of theinfusion, in adition to pre levels.Peak levels must not exceed 50 mg/L (or 50 ug/mL)

20-31 1/10/12, 10:16 AM24



Use of Other AminoglycosidesThere are insufficient data in CF patients for guiding once daily dosing of otheraminoglycosides. If other aminoglycoside use is needed, use conventional dosingguidelines (i.e. every 8 to 12 hours with normal renal function). Because of the rapidclearance of aminoglycosides in CF patients, expert assistance from the pharmacokineticsservice is suggested if administration of other aminoglycosides is needed.

5. TRADITIONAL DOSING GUIDELINESFor patients falling within the exclusion criteria for once-daily dosing traditional dosingguidelines can be used.

a) DOSING• Determine dosing weight as in once-daily dosing guidelines. For patients with edema

or ascites the patients actual body weight should be used to account for drugdistribution into the large extravascular fluid compartments.

• The recommended loading dose for gentamicin or tobramycin is 1.5 - 2.0 mg/kgfollowed by 1.5 mg/kg every eight hours for patients with normal renal function.

• The recommended dose for amikacin is 7.5 mg/kg given every 12 hours for patientswith normal renal function.

b) DOSING IN RENAL INSUFFICIENCYThe initial (loading) dose is the same as for adults with normal renal function. However,the maintenance dosage regimen is adjusted based upon the degree of renal insufficiency.See Table 2 for appropriate interval and percentage of loading dose to be used asmaintenance dose.

20-31 1/10/12, 10:16 AM25



c) SERUM DRUG MONITORINGThe purpose of measuring the serum drug concentration at steady state is to confirm thattherapeutic concentrations have been achieved and drug accumulation has not takenplace. When treatment is anticipated to be >72 hours, pre (trough) and post (peak) pairsshould be obtained after steady state conditions are achieved (with 4th or 5th dose).

Table 2. Maintenance Dose Nomogram for Aminoglycoside Antibiotics (Adults)

Table 3. Target Serum Aminoglycoside Concentrations

GentamicinTobramycin

Amikacin

Desired Post* (peak)

Urinary tract infectionsSerious infectionsSynergy for gram positive infections only(e.g. enterococcus)

Desired Pre (trough)

mg/L

4-66-83-5

<2

mg/L

16-2020-25-

<8* Target post serum concentrations may need to be in excess of 8 mg/L (> 25 mg/L for amikacin) forpatients with severe gram-negative infections (e.g. sepsis, pneumonia, endocarditis).

Determine the recommended Dosing Interval using the Estimated CreatinineClearance (CLcr)Calculate Maintenance Dose as a percentage of the Loading Dose___________________________________________________________________________CLcr Estimated Half-life Dosing IntervalmL/min mL/sec (h) 8 h 12 h 24 h___________________________________________________________________________90 1.5 3.1 84% - -80 1.33 3.4 80 91% -70 1.17 3.9 76 88 -60 1.0 4.5 71 84 -50 0.83 5.3 65 79 -___________________________________________________________________________40 0.67 6.5 - 72% 92%30 0.50 8.4 - 63 8625 0.42 9.9 - 57 8120 0.33 11.9 - 50 7517 0.28 13.6 - 46 7015 0.25 15.1 - 42 67___________________________________________________________________________12 0.20 17.9 - - 61%

___________________________________________________________________________Modified from Sarubbi FA Jr, Hull JH. Ann Int Med 1978;89: 612-18.

20-31 1/10/12, 10:16 AM26



Serum Sampling Technique• Pre (trough) - Immediately before a dose (within 30 minutes)• Post (peak) - 30 minutes after a 1/2-1 hour infusion, or

- 1 hour following an IM injection• Specimen should be taken from opposite limb to the site of drug infusion.• The timing of drug administration and sample collection must be carefully

documented.

Additional serum drug sampling should be carried out twice weekly for most patients. Forpatients with stable renal and hydration status showing good clinical response and lack oftoxicity once weekly serum drug sampling is sufficient.

Patient Information Sheet - Aminoglycoside TreatmentYou have been prescribed an antibiotic which is called an aminoglycoside.Aminoglycoside antibiotics include drugs such as gentamicin, tobramycin and amikacin.Aminoglycosides have been available for the treatment of bacterial infections for over 30years and are highly effective agents. Your doctor has prescribed an aminoglycoside for youbecause they consider it to be the best option to treat the infection you have, at this time.Unfortunately, like most medications, there are potential side effects that may occur whenaminoglycosides are used. Aminoglycosides may cause reversible kidney damage in 5-10%of patients receiving more than 5 days of treatment with the aminoglycoside, and maycause irreversible hearing loss or imbalance and dizziness in less than 1% of patientsreceiving more than 10-14 days of therapy.• To minimize the risk of kidney damage, your care-givers are monitoring your kidney

function weekly, with the use of blood tests.• To minimize the risk of hearing loss, you should report any symptoms of ringing in the

ears, feeling of fullness in the ears, earache, or hearing loss to your care-giversimmediately, so that your aminoglycoside therapy can be re-evaluated.

• To minimize the risk of problems with your balance, you should report any symptomsof dizziness, unsteady walking, and loss of balance to your care-givers immediately, sothat your aminoglycoside therapy can be re-evaluated.

• If it is necessary to treat your infection for more than 14 days, you will undergo ahearing function test. The first test will be done right away and then about 2 weeks afteraminoglycoside therapy begins. Additional testing will also be done at any time thatyou report symptoms of hearing or balance problems.

If you have any additional questions about your aminoglycoside therapy, please speakwith your doctors or the ward pharmacist. Your nurse can arrange for either yourpharmacist or physician to come and speak with you about your aminoglycoside therapy.

20-31 1/10/12, 10:16 AM27


Amphotericin B Deoxycholate Guidelinesfor Intravenous AdministrationAmphotericin B (AMB) is indicated for the treatment of systemic fungal infections and forempiric therapy in febrile neutropenic patients.

ADMINISTRATION• Reconstitute 50 mg vial with 10 mL of sterile water for injection without preservative.

The reconstituted vial is stable for 24 hours at room temperature or if refrigerated.• Further dilute reconstituted vial in D5W to a maximum concentration of 0.1 mg/mL.

If amphotericin B is to be administered via a central line, a concentration of up to 0.25mg/mL may be administered. (Not compatible with NaCl solutions).

• Infuse over 4-6 hours, however the drug may be given over 2 hours if cardiac and renalstatus permit.

DOSAGE• There is no need to administer a test dose as there is no evidence to suggest that a test

dose is predictive of a systemic reaction to AMB and may result in a delay of therapy,especially in life threatening situations.

• Begin therapy with 0.25 mg/kg - 0.5 mg/kg depending on the infection and acuity ofthe problem.

• Monitor pulse, temperature and blood pressure every 15 minutes during the firstinfusion for one hour.

• On the next day the dose may be increased to 1.0 mg/kg depending on tolerance andthe type of infection being treated.

• A dose of 1.0 mg/kg/day should not be exceeded without consulting Infectious Disease.• It is recommended never to exceed a maximum daily dose of 1.5 mg/kg.

SIDE EFFECTS MANAGEMENT/PREVENTION MEASURES

For prevention of adverse 25-50 mg hydrocortisone IV, 650 mg oralsystemic effects acetaminophen and 25-50 mg oral diphen-(i.e. fever, chills, myalgias, hydramine may be administered 30 minutesnausea, vomiting) prior to am photericin B. (There is no need to

premedicate patients not manifesting theseadverse reactions).

Severe chills, rigors 50 mg meperidine IV in 10 mL NS over 5 minutes.(refractory to hydrocortisone)

Phlebitis Rotate the infusion sites and/or double thedaily dose on alternate days and/or administerover 4-6 hours. Administer via central line.

Hypokalemia Serum potassium daily. Potassium supplementsas required, consider amiloride.

Hypomagnesemia Serum magnesium 2 times weekly. Magnesiumsupplements as required.

Renal toxicity Serum creatinine three times weekly. Maintainadequate hydration. If deemed appropriate,500 mL NS may be infused before each dose ofamphotericin B.

20-31 1/10/12, 10:16 AM28


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Amphotericin B Deoxycholate Guidelinesfor Intravenous Administration (cont’d)

Management of Adult Patients on Amphotericin B

Fungal infection suspected/documented - Amphotericin B indicated?

Yes Amphotericin B (See over for Administration and Monitoring)

Indication Dose Empiric Therapy for Febrile Neutropenia 0.6 mg/kg IV dose Invasive Candidiasis 0.5-1 mg/kg IV daily x minimum of 14 days after last (+) blood culture Invasive Aspergillosis 1-1.5 mg/kg IV dailyC. lusitaniae and C. guilliermondi usually resistant to Amphotericin B

Assess fluid status

Overloaded Normal Depleted

Assess Na status

High (>146 mmol/L) Normal (133-146 mmol/L) Low (<133 mmol/L)

Investigate cause Consider 0.45% NaCl Recommend 0.9% NaCl EXCEPTIONS of hypernatremia 1L IV before ± after 500 mL IV before ± after Patients who cannot

each Amphotericin B each Amphotericin B tolerate additional Na dose dose to prevent Na and and/or fluid, e.g. fluid

intravascular volume overloaded, CHF, depletion and pulmonary edema, nephrotoxicity renal failure

Assess K and Mg status

High Normal Low (K > 5.0 mmol/L) (K 3.5-5.0 mmol/L) (K <3.5 mmol/L) (Mg >1.00 mmol/L) (Mg 0.70-1.00 mmol/L) (Mg <0.70 mmol/L)

High-Risk for Hypokalemia/Hypomagnesemia or consequences of same?: Consider • Acute leukemia • CHF

Amiloride • Atrial fibrillation • T1DM 5-10 mg PO bid1 • Moderate-severe hepatic insufficiency

Receiving loop/thiazide diuretics, long-term steroids, laxatives

CAUTION IN: elderly, diabetics, patients with renal or Recommend adrenal insufficiency, hyperkalemia, Amiloride hypermagnesemia, concomitant 5-10 mg PO bid1

administration with ACE inhibitors, NSAIDs 1. Monitor K+ closely. May still need to

give additional K+ supplementation.

No

Yes

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Amphotericin B Deoxycholate Guidelinesfor Intravenous Administration (cont’d)

2 Continuous Infusion - NOT Routinely Recommended.

Administration of Amphotericin B

Infusion Peripheral line - infuse dose over 4-6 hours

- maximum concentration 0.1 mg/mL Central line - infuse dose over 2-4 hours

- maximum concentration 0.25 mg/mL** (concentrations up to 1.4 mg/mL are soluble in D5W and may be consideredin fluid restricted patients)

Premedication Routine premedication NOT recommended. May be given if infusion-related reaction occurs and then as pre-treatment with subsequent doses. Fever /chills/rigors Meperidine 25-50 mg IV Fever Acetaminophen 650 mg PO (max 4 g/day) Nausea/vomiting Diphenhydramine 25-50 mg PO/IV, Metoclopramide 10 mg IV Give premedication 30 minutes prior to Amphotericin B AVOID OTHER NEPHROTOXIN (e.g. NSAIDS, aminoglycosides, vancomycin, etc.)

Routine Monitoring of Amphotericin B Therapy1

Renal deterioration? 1. Ensure sodium supplemented appropriately e.g. doubling of serum creatinine AND from baseline while receiving 2. Suggest twice the dose (1-1.5 mg/kg, Amphotericin B therapy max 1.5 mg/kg) every other day (q48h)

Continue current therapy Further/continued renal deterioration? and monitoring1 e.g. tripling of serum creatinine from baseline

OR serum creatinine ≥ 250 mmol/L

1Routine Monitoring Options:• Cardiovascular status (HR, BP) 1. Lipid-complex Amphotericin B (ABLC)• Respiratory status (RR <20/min dependent (Must be prescribed by Infectious Diseases or

upon baseline and underlying illness) Hematology) OR• Body weight (assess fluid status) 2. Continuous infusion2 of Amphotericin B• Fluid intake and output (Ins/Outs) (same daily dose infused over 24 hours) OR• CBC with differential 3. Micafungin (Must be prescribed by• Serum K/Na/Ca/Mg Infectious Diseases or Hematology)• Renal Function (i.e. Scr/BUN)• Liver function tests

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Yes

Yes

NoNo

20-31 1/10/12, 10:16 AM30


Amphotericin B Lipid Complex (ABLC)Guidelines for Intravenous Administration

Lipid complex formulations of amphotericin B allow for higher doses to be administeredand have lower incidence of adverse events relative to the conventional formulation.However, because lipid complex formulations of amphotericin B are significantly moreexpensive than the deoxycholate formulation ($500/day vs <$50/day for a 75 kg patient),it is necessary to reserve the drug for patients who meet the following criteria:

Evidence of serious systemic fungal infection

Culture/histology evidence for serious systemic fungal infections and/or evidence ofinvasive disease in patients at risk for disseminated fungal infections (i.e. BMT patients)with clinical signs of infection despite antimicrobial therapy.

AND/OR

Evidence of deteriorating renal function

Serum creatinine has doubled since baseline at initiation of therapy or creatinine clearanceis less than 60 mL/minute (hematological malagnancies, BMT patients).

Which is sustained for 48 hours or more despite the use of saline boluses and carefulattention to K and Mg levels and review of other nephrotoxic medications for possiblediscontinuation.

AND/OR

The patient is not a candidate for high dose fluconazole or itraconazole because of lack ofefficacy or adverse events or in the case of IV itraconazole lack of availability as well.

NOTE:

Previous exposure of lipid complex amphotericin B does not automatically infer that apatient will receive the lipid product during a subsequent treatment for fungal infections.(ie hematology patients).

Procedure for Obtaining Amphotericin B Lipid Complex• Initial order by ID or hematology physician in consultation.

• Patient must meet criteria for use.

• Each (ABLC) therapy regimen should be reviewed at least twice weekly by an ID orhematology physician. If renal function appears to be normalizing, the use oftraditional amphotericin B should be strongly considered.

20-31 1/10/12, 10:16 AM31


Recommendations for the Treatment ofStaphylococcus aureus BacteremiaCategory Criteria Therapy

Simple bacteremia All of the following: 7 d IV antibiotics1. TEE on d 5-7 of therapy that was negativefor both vegetations and predisposingvalvular abnormalities2. Negative surveillance blood cultureobtained 2-4 d after starting appropriateantibiotic therapy and removal of focus3. Removable focus of infection4. Clinical resolution (afebrile and nolocalizing complaints attributable tometastatic infection within 72 h of startingtherapy and removal of focus)5. No indwelling prosthetic devices

Uncomplicated One or more of the following: 14 d IV antibioticsbacteremia 1. Predisposing valvular abnormalities

(more than mild regurgitation) but novegetations shown by TEE2. Positive surveillance blood culture3. Superficial, non-removable focus ofinfection4. Persistent signs of infection after 72 hof antibiotic therapy

Endocarditis According to Duke criteria 4-8 wk IV antibiotics

Extracardiac All of the following: 4-8 wk IV antibiotics1. TEE negative for vegetations2. Deep-tissue infection

32-75 1/9/12, 3:03 PM32

UPDATED

April 2

018


PRE-PRINTED ORDER

Management of Peritonitis (Nephrology)

Patient: Allergies:

PPO0394MR_11_09 Sept 8 2011 Original – chart page 1 of 4

1. Investigations Within 48–72h of initiating antibiotic therapy, assess clinical improvement. Consult with physician/nurse

practitioner if there is no improvement Repeat peritoneal dialysis (PD) effluent culture as well as profile with differential q48h for the first week and

until negative culture result obtained Once negative result obtained, continue sending PD effluent weekly until antibiotic treatment has been

completed

2. Medications: Stop empiric antibiotic therapy and choice of subsequent antibiotic therapy based on culture and sensitivity and patient

allergy status. See below for antibiotic options. Intraperitoneal (IP) (6h long dwell) preferred. Intravenous (IV) administration only for patients where IP antibiotics cannot be utilized

i) Gram-positive organisms on culture (Staphylococcus Aureus, Coagulase-Negative Staphylococcus, Streptococcus spp.)

CeFAZolin 20 mg/kg IP or IV daily: (Circle Route of Administration)

Weight less than 60 kg = 1 g Weight 60–80 kg = 1.5 g

Weight greater than 80 kg = 2 g

OR Vancomycin (cephalosporin allergy and/or bacterial resistance to first-generation cephalosporin)

30 mg/kg IP x _______ kg (most recent total body weight) = _______mg IP EVERY 5 DAYS – approximately 3–5 doses

20 mg/kg IV x _______ kg (most recent total body weight) = _______mg IV EVERY 5 DAYS – approximately 3–5 doses

Duration of therapy Staphylococcus aureus = at least 21 days

Other gram-positive organisms =14 days Peritonitis with exit site or tunnel infection =14–21 days

Prescriber’s Signature: Date (yyyy/mm/dd):

Prescriber’s Name Reg. No. Print

32-75 1/9/12, 3:03 PM33


PRE-PRINTED ORDER

Management of Peritonitis (Nephrology)

Patient: Allergies:




2. Medications continued… ii) Enterococcus spp. on culture (Duration of therapy 21 days)

Ampicillin (if sensitive)

Ampicillin 1 g IP daily Ampicillin 1 g IV daily

OR Vancomycin (penicillin allergy and/or ampicillin resistance)

30 mg/kg IP x _________ kg (most total body weight) = ________mg IP EVERY 5 DAYS – approximately 3–5 doses

20 mg/kg IV x _________kg (most total body weight) = ________mg IV EVERY 5 DAYS – approximately 3–5 doses

PLUS Gentamicin

Gentamicin 0.6 mg/kg IP X ____kg (IBW)=_____mg IP daily (round to the nearest 20 mg)

Gentamicin 0.6 mg/kg IV X ____kg (IBW)=_____mg IV daily (round to the nearest 20 mg)

See Section 3 for gentamicin monitoring

iii) Culture Negative PeritonitisContinue initial empiric antibiotic therapy for 14 days (from PPO0395MR)

Repeat PD effluent culture and profile with differential

If culture positive, adjust therapy/duration based on organism identified (see appropriate section i-vii of this PPO for antibiotic options)

If culture still negative and no clinical improvement, consult physician to consider catheter removal and continue initial empiric antibiotic therapy for at least 14 days after catheter removal.

iv) Pseudomonas spp. on culture Select two anti-pseudomonal antibiotics (if feasible) with differing mechanisms that organism is sensitive to and patient is not allergic to: (Duration at least 21 days)

Ciprofloxacin 500 mg po bid If vomiting, ciprofloxacin 400 mg IP daily. Change to po once vomiting resolves

If vomiting, ciprofloxacin 400 mg IV daily. Change to po once vomiting resolves CeftAZIDime 1 g IP daily CeftAZIDime 500 mg IV daily

Piperacillin/tazobactam 3.375 g IV q12h Imipenem/cilastatin 500 mg IV daily (Restricted– See Capital Health Formulary) Gentamicin 0.6 mg/kg IP x _____kg (IBW)= ______mg IP daily (round to nearest 20 mg)

Gentamicin 0.6 mg/kg IV x _____kg (IBW)= ______mg IV daily (round to nearest 20 mg)

Other Antibiotic Order:


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PRE-PRINTED ORDER Management of Peritonitis (Nephrology) Patient: Allergies:




2. Medications continued… v) Single Gram-Negative Organisms on culture

E.coli, Proteus, Klebsiella spp. on culture

Choose two antibiotics (if feasible) based on sensitivity for 14–21 days

CeFAZolin 20 mg/kg IP or IV daily: (Circle route of administration)

Weight less than 60 kg = 1 g Weight 60–80 kg = 1.5 g Weight greater than 80 kg = 2 g

CeftAZIDime 1g IP daily CeftAZIDime 500 mg IV daily

Ciprofloxacin 500 mg po bid

If vomiting, Ciprofloxacin 400 mg IP daily. Change to po once vomiting resolves If vomiting, Ciprofloxacin 400 mg IV daily. Change to po once vomiting resolves Other Antibiotic Order:

Stenotrophomonas spp. on culture

Choose two antibiotics (if feasible) with differing mechanisms based on sensitivity for 21–28 days Trimethoprim/sulfamethoxazole DS (160 mg/800 mg) 1 tablet po daily

CeftAZIDime 1 g IP daily CeftAZIDime 500 mg IV daily Ticarcillin/clavulanate 3.1 g IV q12h (Restricted- See Capital Health Formulary)

Other antibiotic order:

Enterobacter, Citrobacter, Serratia, Morganella and Providentia spp. on culture

Choose two antibiotics (if feasible) with differing mechanisms based on sensitivity

Ciprofloxacin 500 mg po bid If vomiting, ciprofloxacin 400 mg IP daily. Change to oral once vomiting resolves for 14 to 21 days

If vomiting, ciprofloxacin 400 mg IV daily. Change to oral once vomiting resolves Trimethoprim/sulfamethoxazole DS (160 mg/800 mg) 1 tablet po daily Imipenem/cilastatin 500 mg IV daily (Restricted- See Capital Health Formulary)

Gentamicin 0.6 mg/kg IP x_____ kg (IBW) = ____ mg IP daily (round to nearest 20 mg)

Gentamicin 0.6 mg/kg IV x _____kg (IBW) = ____mg IV daily (round to nearest 20 mg) Other Antibiotic Order:


32-75 1/9/12, 3:03 PM35


PRE-PRINTED ORDER Management of Peritonitis (Nephrology) Patient: Allergies:




vi) Polymicrobial Peritonitis on Culture

Multiple gram-negative organisms or mixed gram–negative/gram–positive (high index of suspicious for intestinal origin) (Duration of therapy 14 to 21 days.) Choose one

Metronidazole 500 mg po q12h

If vomiting, metronidazole 500 mg IV q12h

Plus: Choose one Ampicillin (if sensitive) 1 g IP daily Ampicillin (if sensitive) 1 g IV daily

Vancomycin (penicillin allergy and/or ampicillin resistance) 30 mg/kg IP x _______ kg (most recent body weight) = _______mg IP q5days – approximately 3–5 doses

20 mg/kg IV x _______kg (most recent body weight) = ______mg IV q5days – approximately 3–5 doses

Plus: Choose one CeftAZIDime (if sensitive) 1 g IP daily CeftAZIDime (if sensitive) 500 mg IV daily

Ciprofloxacin 500 mg po bid If vomiting, Ciprofloxacin 400 mg IP daily. Change to oral once vomiting resolves

If vomiting, Ciprofloxacin 400 mg IV daily. Change to oral once vomiting resolves

Gentamicin 0.6 mg/kg IP x ______ kg (IBW) = ______ mg IP daily (round to nearest 20 mg)

Gentamicin 0.6 mg/kg IV x ______ kg (IBW) = ______ mg IV daily (round to nearest 20 mg)

Other Antibiotic Order: _____________________________________________________


vii)Fungal Peritonitis

Fluconazole (if sensitive) 200 mg po daily for 10 days If vomiting, fluconazole 200 mg IV daily for 10 days Remove catheter once fungi confirmed by culture

3. Monitoring

Pre (trough) gentamicin level before the fourth dose. Additional serum gentamicin sampling should be carried out twice weekly. Audiograms are recommended at baseline (right away) and again if aminoglycoside therapy anticipated to exceed 14 days

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PRE-PRINTED ORDER

Empiric Management of Peritonitis (Nephrology)

Patient: Allergies:


1) INVESTIGATIONS:

Send cloudy effluent ASAP for gram stain, culture and profile with differential Repeat above q48h for the first week and until negative culture result obtained Once negative result obtained, continue sending PD effluent weekly until antibiotic treatment has been completed

2) MEDICATIONS:

a) Initiate Empiric Antibiotic Therapy: Intraperitoneal (IP) (6h long dwell) preferred

IV administration only in patients whom IP antibiotics cannot be utilized

CeFAZolin 20 mg/kg IP or IV daily: (Circle Route of Administration)

Wt less than 60 kg = 1 g

Wt 60–80 kg = 1.5 g

Wt greater than 80 kg = 2 g

OR for patient allergic to cephalosporin:

Vancomycin:

30 mg/kg IP x ______ kg (most recent total body weight) = ______ mg IP EVERY 5 DAYS

20 mg/kg IV x ______ kg (most recent total body weight) = ______ mg IV EVERY 5 DAYS

PLUS All patients should receive one of the following:

Ciprofloxacin 500 mg po bid

If vomiting, ciprofloxacin 400 mg IP daily. Change to po once vomiting resolves

If vomiting, ciprofloxacin 400 mg IV daily. Change to po once vomiting resolves



If patient allergic to ciprofloxacin, ceftAZIDime 1 g IP daily

If patient allergic to ciprofloxacin, ceftAZIDime 500 mg IV daily

b) Non-Antibiotic Medication:

Hold oral iron, phosphate binders such as calcium carbonate (Tums®) until peritonitis has resolved.

Heparin 500 units/L of Dianeal® fluid IP for fibrin in effluent until clear

Ultrafiltration problems: use 2.5% Dianeal® exchanges (with short dwell times of 2-3 hours) as opposed to longer dwells with 4.25% Dianeal®

c) Subsequent Antibiotic Therapy: Based on 48–72h culture results (See Management of Peritonitis Pre-Printed Order PPO0394MR)

32-75 1/9/12, 3:03 PM37


Treatment of Candidemia

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Drug Therapy1st choice: Amphotericin B 0.6-1.0 mg/kg/day IV

ORFluconazole 400-800 mg/day IV or PO if tolerated*ORMicafungin 100 mg IV daily

Alternate: Amphotericin B 0.7 mg/kg/day IV plusFluconazole 800 mg/day IV or PO for 4-7 days,then Fluconazole 800 mg/day IV or PO*

❖ Continue therapy for 14 days after the last positive bloodculture and/or resolution of signs and symptoms

No

Yes

Suspected or confirmed candidemia

Is the patient neutropenic?

❖ Give at least 1 ophthalmologicexam to exclude candidalendophthalmitis at a time whenthe candidemia is controlled

❖ If the patient was neutropenicwait until they have recovered foreye examination

❖ Removal of intravascular catheters if possibleDrug Therapy1st choice: Amphotericin B 0.7-1.0 mg/kg/day IV

ORLipid formulation Amphotericin B 3.0-6.0 mg/kg/day IVORMicafungin 100 mg IV daily

Alternate: Fluconazole 6-12 mg/kg/day IV or PO if tolerated*❖ Continue therapy for 14 days after the last positive blood culture and/or

resolution of signs and symptoms and resolution of the neutropenia❖ May be necessary to accelerate recovery from neutropenia with GCSF❖ Failure to respond to therapy

❖ Consider susceptibility testing ifthere is a failure to respond totherapy as azole resistant C.albicans, C. glabrata and C.krusei are becoming morecommon

Lipid formulations of Amphotericin B are notinterchangeable and are used when there is acontraindication to conventional Amphotericin B:1. Amphotericin B lipid complex (ABLC); Abelcet2. Liposomal Amphotericin B; Ambisome

References1. CID 2004:38; 161.2. Medical Letter 2008:6(65); 1

If endocarditis is suspected and/or confirmed:Drug Therapy1st choice: Amphotericin B 0.6-1.0 mg/kg/day IV

ORLipid formulation Amphotericin B 3.0-6.0 mg/kg/day IVplus 5-flucytosine 25-37.5 mg/kg PO QID*

Alternate: Fluconazole 6-12 mg/kg/day IV or PO if tolerated*ORMicafungin 100 mg IV daily

❖ Continue therapy for 6 weeks after valve replacement❖ If valve replacement is contraindicated continue fluconazole long term

❖ See also guidelines for fungal infections.

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32-75 1/9/12, 3:03 PM38

UPDATED

Novem

ber 2

018


Cellulitis Guidelines

Definition:Acute spreading inflammation involving the soft tissue, excluding muscle,characterized by recent onset soft-tissue erythema, warmth, swelling andtenderness, considered to be of infective origin, and acquired in the community.This does not include infected surgical wounds or previously treated (<3months) deep diabetic infections.

Grading scale:

Grade I - Symptoms/signs restricted to superficial swelling,erythema, warmth, mild lymphadenopathy, & mildpain; absence of systemic symptoms in patientswithout high risk factors1.

Grade II - Dominant systemic signs – fever, chills lymphangitis&/or rapidly advancing edge.- Mild cellulitis (as defined in Grade I) in high-riskpatients1,2 without frank immunocompromise2.

Grade III - Failure to respond to >48 h of adequate oral antibiotictherapy, severe facial involvement or extensive skininvolvement (i.e. if any dimension of the area of skininvolved is greater than the distance between thepatient’s median wrist crease and the point of theelbow).- History of episodes of cellulitis requiring prolongedintravenous therapy.- Co-morbid conditions necessitating inpatient therapy.

Grade IV - Orbital, joint, or deep hand involvement.- Cellulitis in immunocompromised patients2.- Suspicion of necrotizing, deep-seated infection orsevere sepsis3.

__________________1 Age ≥16 years2 ‘High risk patients’, neutropenia, asplenia, active cancer and/orchemotherapy, SLE, transplant, prosthetic joint or valve, HIV withCD4 count <200, chronic venous insufficiency, chroniclymphedema etc. affecting the infected body part3Severe sepsis = systemic signs/symptoms with evidence of endorgan dysfunction or hypoperfusion

A four level grading system to guide the intensity of treatment according to theclinical presentation and underlying predisposition of the patient.

32-75 1/9/12, 3:03 PM39


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*For cellulitis unresponsive to conventional treatment or that involves an accompanyingabscess or furuncle consider Ca-MRSA (rates in NS purulent SSTI’s ~ 20%). Appropriatetreatment includes incision and drainage and non B-lactam antibiotics such asdoxycycline or trimethoprim/sulfamethoxazole.____________________________________________________________________________________1 See definition.2 Antibiotic treatment must be initiated immediately upon suspicion of diagnosis in patients gradeII to IV.

3 If patient reports shortness of breath or hives within 24 hours of penicillin use, substituteCefazolin/Probenecid with Clindamycin 600 mg or Levofloxacin 500 mg IV.

4 Clinical decision by attending physician (patient too sick), or logistical decision (home supportor patient compliance concerns).

5 Consults to several different disciplines may need to be made simultaneously.

Figure 1: Nova Scotia Adult Cellulitis Algorithm

Infected bite or infectednatural water injury?

Diagnosis ofCellulitis1*

Suspicion ofAbscess?

Uncertain orunripe2 or purulent

cellulitis

Confirmed Appropriate surgicalmanagement.Avoid antibiotics exceptif surrounding area ofcellulitis > 5 cm.

Begin Rx as GradeII. See in ED in 24 hfor re-evaluation.Consider coverageCa-MRSA.

Immediately giveClindamycin 600 mg IVand Ceftriaxone 1 g IVIMMEDIATE REFERRAL

Use the same grading systemfor disposition, but use Table Ifor antibiotic choice.

Consider the possibilityof necrotizing infection?

Grade I Grade II Grade III Grade IV

Cephalexin 500 mgQID po x 7 days or,Cloxacillin 500 mgQID po x 7 daysOr, Clarithromycin500 mg po bid x 7days.

Family doctorand reliablePatient/Family

Follow-upwith FD in48-72 h

Return to EDin 36-48 hif noimprovement

Initial dose ofCefazolin 2 g IV &Probenecid 1-2 g po2,3

Cephalexin 500 mgQID po x 7 days.Or, Cloxacillin 500 mgQID po x 7 daysOr, Clarithromycin500 mg po bid x7 days.

Follow-upwith FD in24-36 h

Return toED in24-36 h if noimprovement

Candidate forhome IV therapy4

Cefazolin 2 g IV+ Probenecid 1-2 g po2,3 daily

Arrange forcloselysupervised homeIV therapy.Cefazolin 2 g IV +Probenecid 1-2 gpo. Change to poregime as forGrade 1, if Grade1 featuresobtained for > 24hours. Follow withFD in 5 days.

Cefazolin 1-2 gIV or Cloxacillin1-2 g2,3

Refer toGen. Medor Fam.Med foradmission

I M M E D I A T ECONSULTS:I.D. for allpatients plus:Necrotizinginfection -surgery, Deephand infection -Plastic Surg.Orbital Cellulitis -Ophthalmology5

Blood Cultures - only in complex infections,immunocompromised or sepsisCBC & ‘Lytes - only if indicated for reasons other than cellulitis.Chem-strips (not lab glucose - to screen for Diabetes Mellitus)

Yes

NoYes

No

No

➝ ➝

Yes

Yes

Family doctorand reliablePatient/Family

➝ ➝

➝

➝

➝

➝

➝

NO➝ ➝ ➝ ➝

➝ ➝ ➝ ➝

➝

➝➝

➝ ➝

➝ ➝

➝ ➝

➝➝

➝➝

➝ ➝

➝ ➝

➝

32-75 1/9/12, 3:04 PM40


1 Treat as per Grade III on Cellulitis algorithm.2 Refer to nearest facility with IV capability, or, if appropriate, contact EHS NS for emergency home administration of IV antibiotics and splinting.3 If evidence of active infection at follow-up, apply cellulitis (mammal bite) guidelines.4 CFI = clenched fist injury.5 High Risk patients-see foot note #2 on page 27.

Recommendations for Antibiotic Prophylaxis of Bite Wounds(the use of this algorithm presumes thorough irrigation anddebridement of the wound)

Uni

nfec

ted

Bite

Wou

nds

Cef

tria

xo

ne

1-2

g I

V a

nd

Fla

gy

l 5

00

mg

tid

po

, sp

lin

t

as a

pp

rop

riat

e, s

ee i

n 2

4 h

2,3

No

Anti

bio

tics

.

Fo

llo

w i

n

24

h3

Am

ox

/Cla

v x

5-7

day

s. F

oll

ow

in

24

h3

< 3

h a

nd

imm

un

e O

K

Low

risk

pt

or

inju

ry

Do

g

Join

t

Oth

er

Oth

er

No

Hig

h

risk

pt

Yes

Gra

de

III1

Co

nsu

lt I

D

Han

ds/

face

Hu

man

CF

I4

Cat

> 3

h

Hig

h

risk

pt

or

inju

ry

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○ ○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○

○ ○ ○

○

○

○

○

○ ○ ○ ○

○

○

▲ ▲

▲▲

▲

▲

▲ ▲ ▲ ▲

▲

▲

▲

▲▲

▲

▲

▲

▲

▲

▲

▲ ▲

▲

▲

or

○

○

▲

▲

Nova Scotia Adult Cellulitis Guidelines

32-75 1/9/12, 3:04 PM41


Infe

ctio

ns o

f inj

urie

s su

stai

ned

in n

atur

al w

ater

or

as a

res

ult

of b

ite w

ound

sC

ircum

stan

ce o

f Orig

inal

Inju

ry:1

Gra

deM

amm

al B

iteSa

lt W

ater

Fres

h W

ater

IAm

ox/C

lav2

875

mg

po B

ID x

Dox

ycyc

line

200

mg

poTM

P-Su

lpha

3 D

S x

1 ta

b7-

10 d

ays

OD

+/-

Cip

roflo

xaci

n 50

0po

BID

or C

ipro

floxa

cin

If Pe

n. A

llerg

y, C

ipro

floxa

cin

mg

po B

ID x

7-1

0 da

ys50

0 m

g po

BID

x 7

-10

days

500

mg

po B

ID p

lus

Clin

dam

ycin

300

mg

QID

x 7

day

s or

Mox

iflox

acin

400

mg

po o

nce

daily

IIC

eftr

iaxo

ne 1

g IV

, the

n po

Cip

roflo

xaci

n 40

0 m

g IV

, the

n po

as

abov

ere

gim

e as

abo

ve

III4

Cef

tria

xone

1-2

g IV

OD

+C

ipro

floxa

cin

400

mg

IV B

IDM

etro

nida

zole

500

mg

BID

x(S

tep

dow

n to

PO

if fu

nctio

ning

gut

)7-

10 d

ays

1 Con

sult

ID if

pre

gnan

t.2 A

mox

icill

in/C

lavu

lana

te3 S

ulfa

met

hoxa

zole

/Trim

etho

prim

Nova Scotia Adult Cellulitis Guidelines

32-75 1/9/12, 3:04 PM42


Clindamycin Intervention ProjectDue to the frequency of the development of antibiotic associated diarrhea and the highcost associated with the use of clindamycin, the Antimicrobial Agents Sub-Committeeencourages physicians to consider the following:

Intra-Abdominal and Other Anaerobic Infections• Unless contraindicated it is suggested that metronidazole 500 mg PO/IV q12 hours be

employed with adjunctive antimicrobials in place of clindamycin.

• Metronidazole has superior coverage of B. fragilis and therefore is the drug of choice.

If staphylococcal/streptococcal coverage is also required,

• Metronidazole can be used in combination with cefazolin as an alternative toclindamycin.

• Compared to clindamycin the combined use of these agents offers:

i) equivalent staph/strep coverage

ii) better coverage for B. fragilis

iii) additional coverage of E. Coli and Klebsiella

iv) cost savings.

Cautions:• To avoid the risk of adverse effects, metronidazole should not be administered with

ALCOHOL-containing products or for 48 hours after discontinuation ofmetronidazole.

• If metronidazole and WARFARIN are administered concomitantly, the INR should bemonitored more frequently.

• Administration of metronidazole in pregnant patients should be avoided especiallyduring the first trimester.

• Dosage adjustment for cefazolin is indicated in patients with renal dysfunction.

• Use cefazolin with caution in patients with a history of penicillin allergy.

32-75 1/9/12, 3:04 PM43


CDAD is an infectious disorder that can develop when toxin-producing C. difficile isacquired as a component of the colonic microflora. If a patient harbouring the organism isthen exposed to certain antimicrobials, C. difficile is able to evade eradication by sporeformation, while many of the bacteria that help maintain normal ecology in the colon aredestroyed. This can result in the uncontrolled overgrowth of C. difficile and the productionof endotoxins that can cause inflammation and cellular damage. When CDAD occurs itcan range from self-limiting diarrhea to life threatening enterocolitis and toxic megacolon.

Diagnosis: Mild to moderate to severe diarrhea accompanied by a positive C. difficilecytotoxin test result.

Agents implicated in the development of CDAD: All antimicrobials and certainantineoplastics with antimicrobial activity have in implicated in the precipitation ofCDAD.

Most commonly implicated agents: Clindamycin, ciprofloxacinSecond and third-generation cephalosporins

Onset of development of CDAD: Ranges from one to two days after initiation of therapyto 10 weeks after drug discontinuation. Most cases occur after several days of therapy oftherapy with the offending agent.

Initial Management of CDAD: Stop the offending agent if feasible and restore fluids andelectrolytes if needed. With mild cases in those who are not elderly or debilitated, thepatient can be monitored for symptomatic improvement for 48 hours before oraltreatment for CDAD is initiated. If symptomatic deterioration occurs, antibiotic therapyfor CDAD should begin immediately.

Drug treatment of CDAD:

Agent Dose/Duration Efficacy Cost for 7 days

Metronidazole 500 mg tid Rapid resolution of $ 0.84 to 1.26

(first line) for 10 to 14 days symptoms within 5 days

Response rate = 95%

Relapse rate = 5 to 15%

Vancomycin 125 mg qid Rapid clinical and $53.67

(second line) for 10 to 14 days bacteriological improvement

within 5 days

Response rate = 97%

Relapse rate = 5 to 15%

Evidence has shown that oral metronidazole to be equivalent to oral vancomycin for thetreatment of mild-moderate CDAD. There appears to be little or no difference in eitherresponse or relapse rates between the two agents. Vancomycin is more costly and theindiscriminate use of vancomycin may have a role in the emergence of vancomycin-resistant enterococci (VRE). Thus oral vancomycin is reserved when CDAD fails torespond to metronidazole or is severe or potentially life-threatening. Vancomycin is alsothe preferred agent for pregnant and nursing mothers. Vancomycin may also beconsidered for patients who are currently receiving warfarin, alcohol-containing productsand are allergic to or highly intolerant of metronidazole.

Treatment of Clostridium Difficile-Associated Disease (CDAD)

32-75 1/9/12, 3:04 PM44


Treatment of Clostridium Difficile-Associated Disease (CDAD) (cont’d)Non-oral therapies: Oral therapy is always preferable for the treatment of CDAD, but theoral route is sometimes not feasible because of gastrointestinal obstruction ormegacolon. Intravenous metronidazole (500 mg q 12h) is recommended for thesepatients. An alternative is vancomycin administered via an nasogastric tube or enemas(with or without therapy with intravenous vancomycin or metronidazole).Monotherapy with intravenous vancomycin is almost never recommended because ofunacceptably low concentrations of vancomycin in the gastrointestinal lumen.

Additional strategies:

Antiperistaltic agents such as loperamide should be avoided as they predispose the patientretention of the C. difficile toxins and possible toxic megacolon or enhance the absorptionof metronidazole and result in treatment failure.

The routine use of bile-sequestering agents such as cholestyramine should be avoided inthe initial management of CDAD. There is lack of evidence to support its role and the drugmay bind oral vancomycin, causing treatment failure. Cholestyramine may have a role inthe treatment of patients with multiple relapse.

The treatment of asymptomatic carriers of C. difficile is not necessary.

Treatment of relapse, reinfection and failure:

15 to 30% of patients will relapse within two months after completing initial therapy.Relapse is defined as a return of symptoms and positive diagnostic test results aftersuccessful antimicrobial therapy for CDAD. Since relapse is unrelated to antimicrobialresistance, the same agent used to treat CDAD initially can be used to treat the relapse.Thus, a patient with relapse treated with oral metronidazole initially should receive asecond 10-day course of metronidazole. Reinfection is difficult to distinguish from relapseand reusing oral metronidazole is appropriate.

Relapse should be distinguished from treatment failure. Relapses generally manifest withinone to four weeks after cessation of therapy and treatment failure is indicated by a lack ofresponse. However all patients (unless severely ill) should be treated with a minimum of 72hours with oral metronidazole before switching to oral vancomycin.

Prevention:

Appropriate antimicrobial selection:

The optimal use of clindamycin, poorly absorbed agents (i.e. cefuroxime) or those withhigh biliary tract excretion (i.e. ceftriaxone) is essential for the prevention of CDAD.

Appropriate infection control measures – contact Infection Control

32-75 1/9/12, 3:04 PM45


Suggested Guidelines for the Treatment of Clostridium difficile-Associated Diarrhea

Diarrhea

History of prior (1-8 weeks) or concurrent exposure to antimicrobials

Look for othercause

Order assay for C.dificile toxin IBD patient

No Treatment (considerflexible sigmoidoscopy or other

investigations to determinecause if persistent diarrhea)

Metronidazole 500 mg IV q12h +/—Vancomycin via rectal enema (500 mgdiluted in 1 L of 0.9% NaCl injection) orthrough pigtail catheter directly intocecum or ileostomy (200 mg or 500mg of vancomycin (400 or 1000 ug/ml)in 0.5 L) QID if tolerated

Vancomycin125 mg po qidx 10-14 days

Metronidazole500 mg po tidx 10-14 days

No further studies

Consider treatment

Reconfirm diagnosis withC.difficile cytotoxin test

No further studies Further work-up

Manage without furtherantimicrobial therapy

Repeat Initial Course of Antibiotic Therapy(resistance to antimicrobials is exceedingly rare)

No further studies

Vancomycin 500 mg QID x 10days + S.boulardii # 500 mgpo BID(begininning on day 7 of vancotherapy) x 4 wksClin Infect Dis 2000;31:1012-17# Caution inimmunocompromized patients

Week Vancomycin Taper1 125 mg QID2 125 mg BID3 125 mg OD4 125 mg qOD5 & 6 125 mg q3 daysAm J Gastroenterol 1985;80:867-8

Vancomycin po x 14 daysfollowed by cholestyramine *4 g tid x 21 days Am JGastroenterol 1997;92: 739-50*cholestryramine should bespaced from all medications byat least 2 hours

Sequential TaperVanco 125 mg q6h x 7-10 daysVanco 125 mg q12hrs +cholestyramine 4 g q12 hrs x 5-7 daysVanco 125 mg OD + cholestyramine4 g q12h x 5-7 daysCholestyramine 4 g q12h x 14 daysAm J Gastroenterol 1982; 77:220-1

Yes No

Positive Negative

• Discontinue causative antibiotics, if feasible +/–substitute with antibiotic less predisposing to CDAD• Restore fluids & electrolytes as needed• Avoid antiperistaltic agents

Is diarrhea moderate/severe?

Yes No

Is patient able to tolerate po meds? Is patient elderly or debilitated?

Yes No

Monitor patientfor 48 hrs

• Is patients allergic to/or unableto tolerate metronidazole?• Does patient have a severityscore ≥ 2*?(see below) Resolution Persistent

DiarrheaYes No

Patient Responds

No Relapse Relapse after Therapy

Positive Negative

Is CDAD moderate/severe?

Yes No

Responds & Nofurther Relapse

Responds &Later Relapses

Yes No

▲ ▲

▲▲

▲

▲

▲ ▲

▲

▲

▲

▲

▲

▲

▲

▲

* CID 2007;45:302 1 Point 2 Points• age > 60 • endoscopic evidence of PMC• T > 38.3°C • ICU admission• albumin < 25• WBC > 15,000 cells/mms

32-75 1/9/12, 3:04 PM46


Prevention of Bacterial Endocarditis 1

Dental procedures that involve manipulation of gingival tissue or the periapicalregion of teeth or perforation of the oral mucosa expose patients with the followingcardiac conditions to a risk of developing endocarditis:i) serious congenital, heart conditions (CHD) - unrepaired or incompletely

repaired cyanotic congenital heart diseases (including palliative shunts andconduits), any repaired CHD with residual defect at the site or adjacent to thesite of prosthetic patch/device; a completely repaired CHD with prostheticmaterial, device during the first 6 months after procedure;

ii) cardiac transplant that develops cardiac valvulopathy;iii) prosthetic cardiac valve or prosthetic material used for cardiac valve repair;iv) prior episode(s) of endocarditis.

The following table was adapted from the American Heart Associationrecommendations published. Circulation April 19, 2007.

DENTAL AND UPPER RESPIRATORY PROCEDURESORAL2 DOSAGE

Amoxicillin3 2 g 1 hour before the procedure

Penicillin allergy:

Clindamycin 600 mg 1 hour before the procedure

OR

Azithromycin or clarithromycin 500 mg one hour before the procedure

OR

Cephalexin ¥ 2 g 1 hour before the procedure only

PARENTERAL2 DOSAGE

Ampicillin 2 g IM* or IV 30 minutes before the procedure

Penicillin Allergy:

Clindamycin 600 mg 30 minutes before the procedure

and 150 mg IV/PO 6 hours later

OR

Cefazolin ¥ 1 g 30 minutes before procedure

¥ Should not be used in individuals with immediate type 1 hypersensitivity reactionto penicillins (urticaria, angioedema, or anaphylaxis).* IM administration should be avoided in patients receiving anticoagulationtherapy.

32-75 1/9/12, 3:04 PM47


1. For patients with previous endocarditis, valvular heart disease, prosthetic heartvalves, most serious forms of congenital heart disease, viridans streptococci arethe most common cause of endocarditis after dental or upper respiratoryprocedures; enterococci are the most common cause of endocarditis aftergastrointestinal or genitourinary procedures.*

2. Oral regimens are more convenient and safer. Parenteral regimens are more likelyto be effective; they are recommended especially for patients with prostheticheart valves, those who have had endocarditis previously, or those takingcontinuous oral penicillin for rheumatic fever prophylaxis.

3. Amoxicillin is recommended because of its excellent bioavailability and goodactivity against streptococci and enterococci.

* Antibiotic prophylaxis against infective endocardidits is recommended in theaforementioned patients for dental procedures that involve manipulation ofgingival tissue or the periapical region of teeth or perforation of the oral mucosa,procedures on respiratory tract involving incision or biopsy of respiratorymucosa and procedures in patients with infected skin, skin structures ormusculoskeletal tissue; however, antibiotic prophylaxis against infectiveendocardidits is not recommended for genitourinary or gastrointestinal tractprocedures [Circulation 2007; 116: 1736-1754].

Prevention of Bacterial Endocarditis(cont’d)

32-75 1/9/12, 3:04 PM48


Treatment of Bacterial Endocarditis

Preface

Bacterial endocarditis is a serious, sometimes life-threatening infectionthat may require surgical, as well as medical therapy, for optimaloutcome.

Management requires a multidisciplinary approach involvinginfectious disease specialists, cardiologists, and cardiac surgeons, withother specialists as dictated by the specific clinical situation

These CDHA guidelines for the antimicrobial therapy of bacterialendocarditis have been arrived at by consensus among ID Divisionmembers based upon the evidence in the literature and our localepidemiology and susceptibility patterns.

32-75 1/9/12, 3:04 PM49


Treatment of Bacterial Endocarditis(cont’d)

Anat

omic

Site

/Dia

gnos

is/

Mod

ifyin

g Ci

rcum

stan

ces

Infe

ctiv

e en

doca

rditi

s -

Nativ

e va

lve

- em

piric

al rx

awai

ting

cultu

res

Infe

ctiv

e en

doca

rditi

s -

Nativ

e-va

lve-

IV il

licit

drug

use

± ev

iden

ce rt

-sid

eden

doca

rditi

s-em

piric

rx

Viri

dans

stre

p, S

. bov

is w

ithpe

nici

llin

G M

IC ≤

0.1 μμμμ μg

/mL

Viri

dans

stre

p, S

. bov

is w

ithpe

nici

llin

G M

IC >

0.1

to <

0.5

μμμμ μg/m

L

Virid

ans

stre

p or

S. b

ovis

with

pen

G M

IC ≥

0.5

and

ente

roco

cci s

usce

ptib

le to

AM

P/p

en G

, van

co

Etio

logi

es(u

sual

)

Viri

dans

stre

p 30

-40%

,“o

ther

” st

rep

15-2

5%,

ente

roco

cci 5

-18%

,st

aphy

loco

cci 2

0-35

%

S. a

ureu

sA

ll ot

hers

rare

Virid

ans

stre

p, S

. bov

is

Virid

ans

stre

p, S

. bov

is,

nutri

tiona

lly v

aria

ntst

rept

ococ

ci, t

oler

ant

stre

p

Susc

eptib

le e

nter

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ci,

virid

ans

stre

p, S

. bov

is,

nutri

tiona

lly v

aria

ntst

rept

ococ

ci

Prim

ary

[(Pen

G 2

0 m

U q

d IV

, div

. q4h

) or

(AM

P 12

g q

d IV

, con

tinuo

us o

r div

.q4

h) +

(cl

oxac

illin

2.0

g q

4h IV

) +ge

ntam

icin

1.0

mg/

kg q

8h IV

]

Clox

acill

in 2

g IV

q4h

+ge

ntam

icin

1.0

mg/

kg q

8h

[(Pen

G 1

2-18

mU

/d IV

, q4h

x 2

wee

ks) P

LUS

(gen

tam

icin

1 m

g/kg

q8h

IV x

2 w

eeks

) if

unco

mpl

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R (P

en G

12-

18 m

U/d

IV, q

4h x

4w

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) if c

ompl

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4 w

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PLUS

gen

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1 m

g/kg

q8h

IVx

2 w

eeks

.

[(Pen

G 1

8-30

mU

/24h

IV, q

4h x

4-

6 w

eeks

) PLU

S (g

enta

mic

in 1

mg/

kg q

8h IV

x 4

-6 w

eeks

)] O

R (A

MP

12 g

/d IV

, q4h

+ g

ent a

s ab

ove

x 4-

6 w

eeks

)

Alte

rnat

ive

Vanc

o 15

mg/

kg q

12h

IV

Vanc

o 15

mg/

kg q

12h

IV

(Cef

triax

one

2 g

qd IV

+ge

ntam

icin

1 m

g/kg

IV q

8hbo

th x

2 w

eeks

). If

alle

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pen

G o

r cef

triax

, use

van

co30

mg/

kg/d

in 2

div

. dos

es x

4w

eeks

Vanc

o 15

mg/

kg IV

q12

h x

4w

eeks

Vanc

o 15

mg/

kg IV

q12

hPL

US g

enta

mic

in 1

-1.5

mg/

kg q

8h IV

x 4

-6 w

eeks

.

Adju

nct D

iagn

ostic

or T

hera

peut

ic M

easu

res

and

Com

men

ts

If pa

tient

not

acu

tely

ill o

r not

in h

eart

failu

re, w

e pr

efer

to w

ait f

or b

lood

cultu

re re

sults

. If i

nitia

l 3 b

lood

cul

ture

s ne

g. a

fter 2

4-48

hrs

, obt

ain

2-3

mor

e bl

ood

cultu

res

befo

re e

mpi

ric rx

sta

rted.

Clo

xaci

llin

+ ge

ntam

icin

may

not

be

adeq

uate

cov

erag

e of

ent

eroc

occi

, hen

ce a

dditi

on o

f pen

icill

inG

pen

ding

cul

ture

s. W

hen

bloo

d cu

lture

s +,

mod

ify re

gim

en fr

om e

mpi

ricto

spe

cific

bas

ed o

n or

gani

sm, i

n vi

tro s

usce

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ilitie

s cl

inic

al e

xper

ienc

e.

If M

RS

A c

arrie

r, va

ncom

ycin

repl

aces

clo

xaci

llin

as th

e em

piric

cho

ice.

Targ

et g

ent l

evel

s: p

eak

3 μg

/mL,

trou

gh <

1 μg

/mL.

Infu

se v

anco

ove

r ≥1

h to

avo

id �

red

man

� s

yndr

ome.

S. b

ovis

sug

gest

s oc

cult

bow

el p

atho

logy

. (N

ew n

ame:

S. g

allo

lytic

us)

Can

use

cefa

zolin

for P

en G

in p

atie

nt w

ith a

llerg

y th

at is

not

IgE-

med

iate

d (e

.g. a

naph

ylax

is).

Alte

rnat

ivel

y, ca

n us

e va

nco.

Tar

get g

ent

leve

ls: p

eak

3 μg

/mL,

trou

gh <

1 μg

/mL.

4 w

eeks

of r

x if

sym

ptom

s <3

mon

ths;

6 w

eeks

of r

x if

sym

ptom

s >3

mon

ths.

Do

not g

ive

gent

onc

e-da

ily fo

r ent

eroc

occa

l end

ocar

ditis

. Tar

get g

ent

leve

ls: p

eak

3 μg

/mL,

trou

gh <

1 μg

/mL.

NOTE

: Dia

gnos

tic c

riter

ia in

clud

e ev

iden

ce o

f con

tinuo

us b

acte

rem

ia (m

ultip

le p

ositi

ve b

lood

cul

ture

s), n

ew m

urm

ur (w

orse

ning

of o

ld m

urm

ur) o

r val

vula

rin

suffi

cien

cy, d

efin

ite e

mbo

li, a

nd e

choc

ardi

ogra

phic

(tra

nsth

orac

ic o

r tra

nses

opha

geal

) evi

denc

e of

val

vula

r veg

etat

ions

. Rev

iew

: NE

JM 3

45: 1

318,

200

1.

Infe

ctiv

e en

doca

rditi

s - N

ativ

e va

lve

- cul

ture

pos

itive

(Con

sens

us o

pini

on o

n rx

by

orga

nism

: JA

MA

274

: 170

6, 1

995)

(Rev

iew:

NE

JM 3

45: 1

318,

200

1)(C

ombi

natio

n rx

: CID

36:

615

, 200

3)

Sugg

este

d Re

gim

ens*

* B

asel

ine

and

wee

kly

audi

omet

ry re

com

men

ded

if am

inog

lyco

side

s us

ed >

2 w

eeks

.

32-75 1/9/12, 3:04 PM50



Anat

omic

Site

/Dia

gnos

is/

Mod

ifyin

g Ci

rcum

stan

ces

Ente

roco

cci:

MIC

stre

ptom

ycin

>20

00 μ

g/m

L; M

IC g

enta

mic

in >

500-

2000

μg/

mL;

no

resi

stan

ce to

peni

cilli

n

Ente

roco

cci:

pen

G M

IC >

16 μ

g/m

L; n

oge

ntam

icin

resi

stan

ce

Ente

roco

cci:

Pen

/AM

P re

sist

ant +

hig

h-le

vel g

ent/s

trep

resi

stan

t +va

nco

resi

stan

t; us

ually

VR

ECo

nsul

tatio

n su

gges

ted

Stap

hylo

cocc

alen

doca

rditi

sAo

rtic

and/

or m

itral

val

vein

fect

ion

Aorti

c an

d/or

mitr

al v

alve

-M

RSA

Tric

uspi

d va

lve

infe

ctio

n(u

sual

ly IV

DUs)

:M

SSA

S. p

neum

onia

S. p

yoge

nes

B, C

, and

G S

trept

ococ

ci

Etio

logi

es(u

sual

)En

tero

cocc

i, hi

gh-le

vel

amin

ogly

cosi

dere

sist

ance

Ente

roco

cci,

intri

nsic

pen

G/A

MP

resi

stan

ce

Ente

roco

cci,

vanc

o-re

sist

ant,

usua

lly E

.fa

eciu

m

Stap

h. a

ureu

s,m

ethi

cilli

n-se

nsiti

ve

Stap

h. a

ureu

s m

ethi

cilli

nre

sist

ant

Stap

h. a

ureu

s,m

ethi

cilli

n-se

nsiti

ve

S. p

neum

onia

S. p

yoge

nes

B, C

, and

G S

trept

ococ

ci

Prim

ary

Pen

G or

AM

P IV

as

abov

e x

8-12

wee

ks (a

ppro

x. 5

0% c

ure)

No

relia

ble

effe

ctiv

e rx

. Can

try

linez

olid

600

mg

IV o

r po

q12h

clox

acill

in 2

g q

4h-6

IV x

4-6

wee

ks +

/- (g

enta

mic

in 1

.0 m

g/kg

q8h

IV x

3-5

d).

NOTE

: Low

dos

e of

gen

t

Vanc

o 1

g IV

q12

h x

4-6

wee

ks+/

- gen

tam

icin

if s

usce

ptab

le

clox

acill

in 2

g q

4-6h

IV p

lus

gent

amic

in 1

mg/

kg q

8h IV

x 2

wee

ks. N

OTE

: Low

dos

e of

gent

Test

pen

icill

in s

usce

ptib

ility

and

cons

ult w

ith ID

Peni

cilli

n G

18

mu/

24 h

(q4h

)X

4 w

eeks

Peni

cilli

n G

18

mu/

24 h

(q4h

)X

4-6

wee

ks +

/- ge

ntam

icin

for

2 w

eeks

Alte

rnat

ive

If pr

olon

ged

pen

G/A

MP

fails

,co

nsid

er s

urgi

cal r

emov

al o

fin

fect

ed v

alve

.

[(Cef

azol

in 2

.0 g

q8h

IV x

4-6

wee

ks) +

/- (g

enta

mic

in 1

.0 m

g/kg

q8h

IV x

3-5

d)].

OR

Vanc

o 15

mg/

kg q

12h

x 4-

6 w

eeks

Line

zolid

600

mg

IV q

12h

If pe

nici

llin

alle

rgy:

Not

cle

ar.

Hig

h fa

ilure

rate

with

2 w

eeks

of

vanc

o +

gent

amic

in (C

ID 3

3: 1

20,

2001

). C

an tr

y lo

nger

dur

atio

n of

vanc

o ±

RIF

(if s

ensi

tive)

.

Adju

nct D

iagn

ostic

or T

hera

peut

ic M

easu

res

and

Com

men

ts10

-25%

E. f

aeca

lis a

nd 4

5-50

% E

. fae

cium

resi

stan

t to

high

gen

t lev

els.

May

be

sens

itive

to s

trept

omyc

in, c

heck

MIC

.C

ase

repo

rt of

suc

cess

with

com

bina

tion

of A

MP,

ME

R, a

nd v

anco

(S

cand

J In

f Dis

29:

628

, 199

7).

Avo

id c

epha

losp

orin

s in

pat

ient

s w

ith im

med

iate

alle

rgic

reac

tion

tope

nici

llin;

cef

azol

in fa

ilure

s re

porte

d (C

ID 3

7: 1

194,

200

3).

No

defin

ite d

ata,

pro

or c

on, o

n on

ce-d

aily

gen

tam

icin

for S

. aur

eus

endo

card

itis.

At p

rese

nt, f

avor

q8h

dos

ing

x 3-

5 d.

↑ re

cogn

ition

of I

V c

athe

ter-

asso

ciat

ed S

. aur

eus

endo

card

itis.

May

nee

dTE

E to

det

ect e

ndoc

ardi

tis.

23%

of S

. aur

eus

bact

erem

ia in

ass

ocat

ion

with

IV c

athe

ter h

ad e

ndoc

ardi

tis (

CID

115

: 106

& 1

15, 1

999)

; if T

EE

neg

,on

ly n

eed

2 w

eeks

of t

hera

py fo

r IV-

rela

ted

S. a

ureu

s ba

cter

emia

.

2-w

eek

regi

men

not

reco

mm

ende

d if

met

asta

tic in

fect

ion

(e.g

.os

teo)

, lef

t-sid

ed e

ndoc

ardi

tis, o

r MRS

A.2

repo

rts o

f suc

cess

with

4-w

eek

oral

regi

men

; CIP

750

mg

bid

+ R

IF 3

00m

g bi

d. L

ess

than

10%

pts

had

MR

SA

(LN

2: 1

071,

198

9; A

JM 1

01: 6

8,19

96).

Sugg

este

d Re

gim

ens*

Vanc

o 15

mg/

kg q

12h

Plus

gen

t 1-1

.5 m

g/kg

q8h

(no

sing

le d

ose)

x 4-

6 w

eeks

32-75 1/9/12, 3:04 PM51



Anat

omic

Site

/Dia

gnos

is/

Mod

ifyin

g Ci

rcum

stan

ces

Met

hici

llin

resi

stan

ce(M

RSA)

Slow

-Gro

win

g fa

stid

lous

Gm

-neg

. bac

illi

Barto

nella

spe

cies

Infe

ctiv

e en

doca

rditi

s -

cultu

re n

egat

ive

Feve

r, va

lvul

ar d

isea

se, a

ndE

CH

O v

eget

atio

ns ±

em

boli

and

neg.

cul

ture

s

Infe

ctiv

e en

doca

rditi

s -

Pros

thet

ic v

alve

- em

piric

ther

apy

(cul

ture

s pe

ndin

g)

Ear

ly (<

2 m

onth

s po

st-o

p)

Late

(>2

mon

ths

post

-op)

Etio

logi

es(u

sual

)St

aph.

aur

eus,

met

hici

llin-

resi

stan

t

HACE

K gr

oup

(see

Com

men

ts) (

May

o C

lin P

roc

72: 5

32, 1

997)

B. h

ense

lae,

B. q

uint

ana

S. e

pide

rmid

is, S

. aur

eus.

Rar

ely,

Ent

erob

acte

nace

ae,

diph

ther

oids

, fun

gi

S. e

pide

rmid

is, v

irida

nsst

rep,

ent

eroc

occi

, S. a

ureu

s

Prim

ary

Vanc

o 15

mg/

kg q

12h

x 4-

6 w

eeks

Ceftr

iaxo

ne 2

.0 g

qd

IV x

4 w

eeks

Alte

rnat

ive

Fails

/into

lera

nt to

van

co, c

antry

line

zolid

600

mg

IV o

r po

q12h

AMP

12 g

qd

(div

. q4h

) x 4

wee

ks +

gen

tam

icin

1.0

mg/

kg q

8h IV

x 4

wee

ks

Adju

nct D

iagn

ostic

or T

hera

peut

ic M

easu

res

and

Com

men

tsFo

r MR

SA

, no

diffe

renc

e in

dur

atio

n of

bac

tere

mia

or f

ever

bet

wee

n pt

s rx

with

van

co o

r van

co +

RIF

(A

nIM

115

: 674

, 199

1).

HACE

K (a

cron

ym fo

r Hem

ophy

lus

para

influ

enza

e, H

. aph

roph

ilus,

Actin

obac

illus

, Car

diob

acte

rium

, Elk

enel

la, K

inge

lla).

H. a

phro

philu

sre

sist

ant t

o va

nco,

clin

da a

nd m

ethi

cilli

n. F

or H

emop

hilu

s, s

ee C

ID 2

4:10

87, 1

997.

Dx: I

mm

unof

luor

esce

nt a

ntib

ody

titer

≥1:

800;

blo

od c

ultu

res

only

occ

.po

sitiv

e, o

r PC

R.

Surg

ery:

Ove

r 50%

pts

requ

ire v

alve

sur

gery

; rel

atio

n to

cur

e un

clea

r.B

. qui

ntan

a tra

nsm

itted

by

body

lice

am

ong

hom

eles

s; a

sym

ptom

atic

colo

niza

tion

of R

BC

s de

scrib

ed (

Ln 3

60: 2

26, 2

002)

.

Ear

ly s

urgi

cal c

onsu

ltatio

n ad

vise

d. W

atch

for e

vide

nce

of h

eart

failu

re.

Sugg

este

d Re

gim

ens*

Etio

logy

in 3

48 c

ases

stu

died

by

sero

logy

, cul

ture

, his

topa

th &

mol

ecul

ar d

etec

tion:

C b

urne

tii 4

8%, B

arto

nella

sp.

28%

and

rare

ly (A

biot

roph

ia e

lega

nd, M

ycop

lasm

aho

min

is, L

egio

nella

pne

umop

hila

, Tro

pher

yma

whi

pple

i — to

geth

er 1

%) &

rest

with

out e

tiolo

gy id

entif

ied

(mos

t on

antib

iotic

s). E

mph

asis

is o

n di

agno

sis.

See

spe

cific

orga

nism

for t

reat

men

t reg

imen

s.

Opt

imal

rx e

volv

ing.

Ret

rosp

ectiv

e &

ope

n pr

ospe

ctiv

e tri

als

supp

ort

gent

amic

in 3

mg/

kg IV

onc

e da

ily x

min

imum

of 1

4 da

ys +

dox

y 10

0m

g po

q12

h x

4-6

wee

ks

Vanc

o 15

mg/

kg q

12h

IV +

gen

tam

icin

1.0

mg/

kg q

8h IV

32-75 1/9/12, 3:04 PM52



Out

pati

ent T

reat

men

tPa

tien

ts w

ith

org

anis

ms s

usce

ptib

le to

Cef

tria

xon

e w

ould

ben

efit

from

on

ce d

aily

dos

ing

of C

eftr

iaxo

ne

2 g

to fa

cilit

ate

hom

e IV

ther

apy

once

disc

har

ged

from

hos

pita

l.

Anat

omic

Site

/Dia

gnos

is/

Mod

ifyin

g Ci

rcum

stan

ces

Infe

ctiv

e en

doca

rditi

s -

Pros

thet

ic v

alve

- po

sitiv

ebl

ood

cultu

res

Sur

gica

l con

sulta

tion

advi

sed:

retro

spec

tive

anal

ysis

sho

ws

↓ m

orta

lity

of p

ts w

ith S

.au

reus

end

ocar

ditis

if v

alve

repl

aced

dur

ing

antib

iotic

rx(C

ID 2

6: 1

302

& 1

310,

199

8);

also

, ret

rosp

ectiv

e st

udy

show

ed ↑

risk

of d

eath

2°

neur

o ev

ents

in a

ssoc

. with

Cou

mad

in rx

Infe

ctiv

e en

doca

rditi

s -Q

feve

r

Etio

logi

es(u

sual

)S

taph

. epi

dem

idis

Sta

ph. a

ureu

s

Viri

dans

stre

p. e

nter

ococ

ci

Ent

erob

acte

riace

ae o

r P.

aeru

gino

sa

Can

dida

, asp

ergi

llus

Cox

iella

bur

netti

i

Prim

ary

Alte

rnat

ive

Adju

nct D

iagn

ostic

or T

hera

peut

ic M

easu

res

and

Com

men

tsIf

S. e

pide

rmid

is is

sus

cept

ible

to C

loxa

cilli

n in

vitr

o (n

ot c

omm

on),

then

subs

titut

e C

loxa

cilli

n fo

r van

co.

In th

eory

, cou

ld s

ubst

itute

Cip

ro fo

r Pip

erac

illin

, but

no

clin

ical

dat

a.

Hig

h m

orta

lity.

Val

ve re

plac

emen

t plu

s an

tifun

gal t

hera

py s

tand

ard

ther

apy

but s

ome

succ

ess

with

ant

ifung

al th

erap

y al

one

(CID

22:

262

,19

96).

Dx: I

gG C

F an

tibod

y of

1:2

00 to

pha

se I

antig

en d

iagn

ostic

of c

hron

ic Q

feve

r (Ln

ID 3

:709

, 200

3).

Sugg

este

d Re

gim

ens*

(Van

co 1

5 m

g/kg

q12

h IV

+ R

IF 6

00 m

g B

ID)

x 6

wee

ks +

gent

amic

in 1

mg/

kg q

8h IV

x 1

4 d

See

infe

ctiv

e en

doca

rditi

s, n

ativ

e va

lve,

cul

ture

pos

itive

Amin

ogly

cosi

de (t

obra

if P

. aer

ugin

osa)

+ (P

iper

acill

in o

rC

efta

zidi

me)

Amph

o B

± an

azo

le, e

.g. f

luco

nazo

le

Doxy

100

mg

po b

id +

hyd

roxy

chlo

roqu

ine

600

mg/

d x

1.5-

3 ye

ars

Met

hici

llin

sens

itive

: (cl

oxac

illin

2.0

g q

4h IV

+ R

IF 6

00 m

g B

ID) x

6 w

eeks

+ g

enta

mic

in 1

.0 m

g/kg

q8h

IV x

14

d.M

ethi

cilli

n re

sist

ant:

(Van

co 1

5 m

g/kg

q12

h IV

+ R

IF 6

00 m

g B

ID) x

6 w

eeks

+ g

enta

mic

in 1

.0 m

g/kg

q8h

IV x

14

d.

32-75 1/9/12, 3:04 PM53


Temp (po) ≥38.5°C or >38°C X 2 in 12hours and ANC ≤0.5 x 109 1

1. Clinical assessment2

2. Microbiological assessment culturesof blood, urine, sputum and otherobvious sites of infection

3. Radiological assessment (Cxray)

Imipenem 500 mg IV q 6h3

Afebrile(Temp < 38.5°C)

Clinically orMicrobiologicallyDefined Infection2

ANC >0.5rising X 48 h

ANC ≤0.5 by day 7and clinically well

ANC ≤0.5 by day 7 &high risk (ANC ≤0.1,mucositis, unstable)

Continue broad spectrumantibiotics (modify coverageif necessary) until afebrile ≥total of 5-7 days OR ANC≥0.5. Treat specific infectionfor at least 7-10 days2,4,7

D/C Ab- 48 hAF& ANC>0.5

Continueantibiotics untilafebrile for 5-7days.

Continue originalempiric regimenuntil ANC ≥0.5

Continue antibiotics for2 weeks max. OR ANC>0.5

Persistent Fever(Temp ≥38.5°C)

Modify Therapy2-6

ReassessDay5-78

Persistent Fever(Temp ≥38.5°C) andunresolving neutropenia

Consider AmphotericinB 0.6-1 mg/kg IV daily9

Reassess10 ➝

➝➝

➝

➝➝

➝➝

➝

➝ ➝

➝➝ ➝➝

➝➝ ➝

➝➝ Day3-5

No ClinicallyDefined Infection2

➝

Febrile Neutropenia - High Risk Inpatient

Intolerance/nephrotoxicity

➝

ABLC (Abelcet) 5 mg/kg daily

➝

Intolerance/nephrotoxicity ➝

Micafungin100 mg daily ➝

➝

32-75 1/9/12, 3:04 PM54


High Risk Febrile NeutropeniaFootnotes1. ANC: Absolute Neutrophil Count.

2. Clinically defined infections: It is important to remember that patients withchemotherapy induced febrile neutropenia need both broad spectrum cover-age, as well as coverage for specific infections. For initial management ofclinically defined infections. In addition to meropenem, consider:(i) Severe Mucositis/Oral Lesions: Yeast/fungal, and HSV cultures.(ii) Documented Line Infection or Sepsis: Vancomycin 1 g IV q12h if

Coagulase-negative staphylococcus (CNST) or MRSA isolated. If suspectedline infection, may consider adding Vancomycin. Discontinue if culturesare negative after 48 hours and/or decrease in clinical suspicion.

(iii) C. difficile diarrhea suspected or documented, ADD metronidazole.(iv) Pulmonary Infiltrates: Consider BAL: for RSV, CMV, PCP, Legionella &

fungus.

3. Documented Hypersensitivity to B-Lactam Antibiotics: Ciprofloxacin 400 mgIV q12h +/- gentamicin 6 mg/kg IV q24h. Vancomycin should be added forbroader gram positive coverage: Consider an ID consult.

4. Deterioration: Patients who deteriorate (e.g. become hypotensive or confused)while still neutropenic and on any combination of antibiotics need carefulreassessment for a source of infection, as well as the addition/change ofantibiotics. Vancomycin may be added empirically in this instance pendingculture results. If culture(s) negative after 48 hours, discontinue.

5. Pathogen Isolated (microbiologically defined infection): Maintain initialbroad-spectrum regimen, unless sensitivities indicate that a pathogen isinadequately covered. Culture documented Pseudomonas infections shouldalways be treated with two agents to which the bacteria is susceptible. AddVancomycin for documented gram positive infections until susceptibilityconfirmed.

6. Renal Function: Monitor serum creatinine at least 3x per week while on anaminoglycoside. If baseline SCr >200 mmol/L or estimated ClCr <70 mL/minavoid adding an aminoglycoside; add ceftazidime to meropenem if doublecoverage required (ie Pseudomonas).

7. Clinically or Microbiologically Defined Infection and Afebrile at Day 4:Continue broad spectrum coverage until afebrile 5-7 days OR ANC ≥0.5 x 109/L.Continue coverage for specific infection for at least 7-10 days AND until clinicalsymptoms have resolved AND ANC >0.5 x 109/L, AND afebrile for 5 days.Duration of antibiotics should be assessed on an individual basis.

8. If still persistently febrile and ANC >0.5, antimicrobials may be stopped after 4-5days of treatment and patient reassessed.

9. Amphotericin B: Consult hospital guidelines for the use of amphotericin B.

10. Consider stopping antimicrobials after 2 weeks of treatment for ANC 0.2-0.5 ifno infectious etiology identified and condition is stable.

32-75 1/9/12, 3:04 PM55


{Paraphrased from Finberg RW, Talcott JA. N Eng J Med 1999; 341: 362-3}

The treatment of fever and neutropenia has evolved with the development of bothnew antimicrobial drugs and new strategies for using them. The first effective treatmentfor patients with fever and neutropenia was the combination of an antipseudomonalpenicillin, carbenicillin, and gentamicin in a strategy of early empirical therapy triggeredby fever alone.

In the 1980’s, the options for antibiotic treatment improved. A large, randomizedstudy demonstrated that a single broad-spectrum drug, ceftazidime, could safely replacethe standard combination of an antipseudomonal penicillin and an aminoglycoside.Despite this finding, because of their previous experience with rapidly fatal pseudomonasinfections, wary clinicians were reluctant to use ceftazidime alone in patients whooften were very ill from intensive chemotherapy.

However, risk-assessment studies began to refine clinicians intuitions about the medicalinstability of their patients. A retrospective study by Talcott et al. of 261 episodes offever and neutropenia treated in the hospital provided justification, in part, for theanxiety of clinicians. In one of five episodes, serious, potentially life-threatening medicalcomplications developed, such as hypotension, respiratory failure and altered mentalstatus. However, not all patients were at similarly high risk. Within 24 hours ofhospitalization, three high-risk groups, could be identified: 1. Patients who were alreadyinpatients when fever and neutropenia developed; 2. Outpatients who needed acutehospital care for problems in addition to the fever and neutropenia; and 3. Clinicallystable outpatients with uncontrolled cancer (those with acute anticancer therapy). Allthe remaining patients - a group that comprised 70 percent of the outpatients - wereby default at low risk. The validity of these risk groups was later confirmed. For patientsin the three high-risk groups, the rate of medical complications was 36 percent, and20 percent of such patients died. For the low-risk patients, the complication rate was 2percent, and none died.

The ability to make distinctions about risk offered new possibilities for treatment. Iffever and neutropenia do not always have the same clinical significance, then thestrategy for treating them may vary according to circumstance. For example, clinicianswho initially were wary of singe-drug therapy with ceftazidime often were morecomfortable using it for low-risk patients. But there were other possible innovationswith important economic implications. If a single intravenous antibiotic could be usedto treat low-risk patients, why not still cheaper and more convenient oral antibiotics?Even more radically, why not send apparently stable patients home for treatment andavoid incurring the cost of an inpatient bed? A more recent paper validated a scoringsystem to predict risk.

Attached are two recent reports from the N Eng J Med1,2 which involve large, prospective,randomized studies of low-risk patients (defined variously by the investigators) thatexpand our options for the management of fever and neutropenia in patients withcancer. The results of these studies show that oral antibiotics may be safely substitutedfor intravenous antibiotics in low-risk patents with fever and neutropenia. Now thatthese studies have provided us with more convenient, versatile antibiotic strategies fortreating low-risk patients with fever and neutropenia, when should we use them? Dothese studies of oral therapy justify our using outpatient treatment? The authors of

Low Risk Febrile Neutropenia

32-75 1/9/12, 3:04 PM56


both of these rigorous, careful studies, which were designed to assess the relativeefficacy of antibiotic regimens given to inpatients, caution that they do not. Althoughclinical experience with the treatment of patient with fever and neutropenia on anoutpatient basis has grown in the past decade, this approach has yet to be validated inlarge, randomized studies designed to assess this critical question: Is outpatient treatmentof fever and neutropenia, away from the watchful eyes and readily available emergencyequipment of the hospital, as safe as inpatient treatment, or at least safe enough?

In the largest study conducted to date, Malik3 and colleagues examined 169 episodesof fever and neutropenia and found that inpatients and outpatients treated withofloxacin alone were equally likely to have their fever and neutropenia resolve withoutrequiring a change in their antibiotic regimen. Although this finding indicates thatidentical regimens have equal efficacy in inpatients and outpatients, it says little aboutthe safety of outpatient treatment. Three patients in the outpatient group died; at leastone of these deaths was apparently preventable.

1. N Engl J Med, July 29, 1999; 341: 305-11.2. N Engl J Med, July 29, 1999; 341: 312-18.3. Am J Med, 1995; 98: 224-31.4. Klastersky J, Paesmans M, Rubenstein EB et al. The multinational association for

supportive care in cancer risk index: A multinational scoring system for identifyinglow-risk febrile neutropenic cancer patients. JCO 2000; 18 (16); 3038-3051.

32-75 1/9/12, 3:04 PM57


A Potential Step by Step ManagementProgram for Low-Risk Febrile Neutropenia

This protocol should only be activated after discussionwith the medical oncologist or hematologist on call

Outpatient Management of the Low Risk Febrile Neutropenic (FN) PatientSafe management of the FN patient relies on a careful risk assessment to identify thoseindividuals who can be treated in the outpatient setting. Outpatient management is intendedonly for stable patients who can be expected to do well. Patients with acute leukemia are notcandidates for outpatient management of febrile neutropenia.

Definitions:• Fever is an oral temperature ≥38°C on 2 occasions at least 12 hours apart or a single oral

temperature ≥38.5°C.• Neutropenia is an absolute neutrophil count (ANC) ≤0.5x109/L as determined by an

automated differential.

Patient Assessment:If the patient will be compliant with outpatient management recommendations ANDLives within 30 minutes of a hospital and has 24 hour live-in support, ANDCan be assessed daily by a physician, he/she may be eligible for outpatient therapy.Answer all of the following questions about the patient:

Yes No1. The patient has hypotension (systolic BP <90 mmHg systolic or 40 mmHg ___ ___

less than patient’s normal)2. The patient has a compromised mental status or is incompetent ___ ___3. The patient has respiratory distress ___ ___4. The patient has abdominal pain, vomiting, mucositis or diarrhea ___ ___5. The patient has gross bleeding or severe bruising ___ ___6. The patient needs parental fluid therapy or pain control ___ ___7. The ANC is expected to take >10 days to recover ___ ___8. There is evidence of deep organ or tissue infection (e.g.: pneumonia, ___ ___

pyelonephritis)9. The temperature is >39°C and the ANC ≤ 0.1x109/L ___ ___10. There is a coexistent medical condition requiring admission ___ ___11. The patient has recently received prophylactic or therapeutic antibiotics ___ ___

(other than sulfamethoxazole-trimethoprim)

If the answer to any of the above is YES, the patient is NOT a candidate for outpatientantibiotic therapy for febrile neutropenia.

Patient Scoring:If the patient is a candidate for outpatient antibiotic therapy, complete the following checklist:

Characteristic Value

• Burden of illness: no or mild symptoms 5• No hypotension 5• No chronic obstructive lung disease 4• Solid tumour or no previous fungal infection 4• No dehydration 3• Burden of illness: moderate symptoms 3• Outpatient status 3• Age <60 years 2

If the score adds to ≥21 the patient may be considered for outpatient antibiotic therapy

32-75 1/9/12, 3:04 PM58


Outpatient Antibiotic Therapy

Oral

Ciprofloxacin* 750 mg BIDand

Amoxicillin-Clavulanate875 mg BID

* consider potential fordrug interactions

Moxifloxacin* 400 mg OD

Management

1. Order a CBC and differential, BUN, creatinine, urinalysis, blood and urine cultures, andchest XRAY.

2. The patient should be given the first dose of antibiotics and observed in the medical dayunit (MDU) or Emergency Department (ED) for 4 hours, monitoring heart andrespiratory rates, blood pressure with orthostatic measurements, temperature, and pulseoximetry every 2 hours at a minimum.

3 If the patient remains clinically stable and fulfills all criteria, the patient can be dischargedto home with the appropriate prescription (5 day supply with 1 repeat) and specificinstructions on how to take the antibiotics and on follow up with the MDU at 10AM thefollowing day.

4. Dose adjustments are required for ciprofloxacin and amoxicillin clavulanate in thepresence of renal insufficiency. Give the first doses and contact pharmacy for advice onfurther dosing recommendations.

5. The patient will be seen daily by the physician or physician clinical associate for thepatient’s service until afebrile and asymptomatic, or hospitalized if necessary.

6. If the patient remains febrile for more than 5 days, admission is required and antibioticsreassessed.

7. Antibiotics will be continued for 5-10 days and until the ANC is >0.5x109/L and thepatient afebrile for ≥72 hours. Oral antibiotics should replace IV as soon as tolerated.

8. The patient should have a CBC with differential and creatinine every 48 hours at aminimum.

Prepared by the Divisions of Infectious Diseases, Medical Oncology, andHematology and the Pharmacy Department, CDHAMarch 2005/Revised 07/05, 12/05, 05/06, 05/06, 06/06

If penicillin allergic

32-75 1/9/12, 3:04 PM59


Empiric Therapy of Fungal InfectionsIn

fect

ion

Usu

al P

atho

gens

Reco

mm

ende

d Em

piri

c Th

erap

yRe

com

men

ded

Dos

eRe

com

men

ded

Dur

atio

nC

omm

ents

Can

dida

Can

didu

ria

Can

dida

spp

*As

ympt

omat

ic•

Usu

ally

ass

ocia

ted

with

fore

ign

body

in u

rinar

yTr

eatm

ent n

ot re

com

men

ded

trac

t. Re

mov

al o

f urin

ary

cath

eter

or s

tent

r esu

ltsun

less

hig

h ris

k†in

40%

era

dica

tion

of c

andi

duria

but

onl

y 20

%if

subs

eque

ntly

repl

aced

.Sy

mpt

omat

ic/H

igh

Risk

†*

Fluc

onaz

ole

may

not

be

effe

ctiv

e ag

ains

t C.

Fluc

onaz

ole

200

mg

PO d

aily

7-14

day

skr

usei

and

som

e st

rain

s of

C. g

labr

ata.

C. l

usita

niae

may

be

resis

tant

to a

mph

oter

icin

B.

Alte

rnat

ive

** B

ladd

er ir

rigat

ion

with

am

phot

eric

in B

has

Am

phot

eric

in B

2 **

0.3-

0.5

mg/

kg/d

IV7-

14 d

ays

been

use

d to

trea

t can

dida

l cys

titis

but d

oes

not

trea

t inf

ectio

ns b

eyon

d th

e bl

adde

r.-

Pers

isten

t can

didu

ria in

imm

unoc

ompr

omise

dpa

tient

s w

arra

nts

US

or C

T of

kid

ney.

†H

igh

Risk

:•

neut

rope

nia

• re

nal t

rans

plan

t pat

ient

s•

patie

nts

unde

rgoi

ng u

rolo

gica

l pro

cedu

res.

Esop

hage

alC

andi

da a

lbic

ans

Fluc

onaz

ole

200

mg

PO fi

rst d

ay-

Alw

ays

indi

cativ

e of

imm

unos

uppr

essio

nC

andi

dias

isO

ccas

iona

llyth

en 1

00 m

g PO

dai

lyno

n-al

bica

ns s

ppRe

fract

ory

2-3

wee

ks a

fter c

linic

alFl

ucon

azol

e40

0-80

0 m

g po

dai

ly-b

idim

prov

emen

tor A

mph

oter

icin

B o

r0.

5 m

g/kg

/d IV

Mic

afun

gin

100

mg

IV d

aily

Inva

sive

Gen

eral

Man

agem

ent

Can

didi

asis

/- R

emov

al o

f cen

tral

ven

ous

and/

or p

erito

neal

dia

lysis

cat

hete

rs g

ener

ally

reco

mm

ende

d in

non

-neu

trop

enic

pat

ient

s bu

t con

trov

ersia

l for

neu

trop

enic

Can

dide

mia

patie

nts

as s

ourc

e of

ten

from

GI t

ract

.- D

iscon

tinue

bro

ad s

pect

rum

ant

ibio

tics

if po

ssib

le.

- Ser

ial b

lood

cul

ture

s (m

inim

um d

aily

x3)

to e

nsur

e st

erili

zatio

n ev

ery

2-3

days

unt

il bl

ood

cultu

res

nega

tive.

- Fun

dosc

opic

exa

min

atio

n sh

ould

be

done

.- F

or p

ositi

ve C

andi

da s

pp c

ultu

res:

• C

. gla

brat

a - s

ome

resis

tanc

e w

ith lo

w d

ose

fluco

nazo

le b

ut c

an b

e ov

erco

me

with

hig

h do

se th

erap

y.•

C. k

ruse

i - re

sista

nt to

fluc

onaz

ole

• C

. lus

itani

ae, C

. gui

llier

mon

dii -

usu

ally

resis

tant

to a

mph

oter

icin

B.

32-75 1/9/12, 3:04 PM60


Empiric Therapy of Fungal Infections (cont’d)

Infe

ctio

nU

sual

Pat

hoge

nsRe

com

men

ded

Reco

mm

ende

d D

ose

Reco

mm

ende

d D

urat

ion

Com

men

tsEm

piri

c Th

erap

y

Can

didi

a al

bica

nsFl

ucon

azol

e80

0 m

g IV

load

ing

dose

min

imum

14

days

afte

r las

t*

Usu

ally

ass

ocia

ted

with

pro

sthe

ticC

andi

dia

trop

ical

is*or

then

400

-800

mg

IV/P

O d

aily

posit

ive

bloo

d cu

lture

devi

ce, e

spec

ially

cen

tral

ven

ous

cath

eter

s.C

andi

da p

arap

silos

is*A

mph

oter

icin

B0.

6-1

mg/

kg/d

IVan

d re

solu

tion

of s

igns

and

- Am

phot

eric

in B

or c

aspo

fung

inC

andi

da g

labr

ata

sym

ptom

sre

com

men

ded

empi

rical

ly if

:C

andi

da k

ruse

iM

icaf

ungi

n10

0 m

g IV

dai

ly•

hem

odyn

amic

ally

uns

tabl

e•

neut

rope

nic

(AN

C <

0.5

x109 /

L)•

susp

ect n

on-a

lbic

ans

Can

dida

spp

.

Empi

ric

Trea

tmen

t of

Can

dida

spp

Am

phot

eric

in B

0.6-

0.7

mg/

kg/d

IVPe

rsis

tent

Feb

rile

Aspe

rgill

usAl

tern

ativ

eN

eutr

open

ia P

roto

col

Mic

afun

gin

100

mg

IV d

aily

(Hig

h Ri

sk)

or ABL

C5

mg/

kg/d

IV

Empi

ric

Trea

tmen

t of

Can

dida

spp

Fluc

onaz

ole

400

mg

IV/P

O d

aily

Pers

iste

nt F

ebri

leAl

tern

ativ

eN

eutr

open

ia P

roto

col

Mic

afun

gin

100

mg

IV d

aily

(Low

Risk

)or A

BLC

5 m

g/kg

/d IV

Can

dida

Hep

atos

plen

icC

andi

da s

ppA

mph

oter

icin

B0.

6-0.

7 m

g/kg

/d IV

3-6

mon

ths

and

reso

lutio

n- F

luco

nazo

le m

ay b

e gi

ven

afte

rC

andi

dias

isor

or c

alci

ficat

ion

of ra

diol

ogic

1-2

wee

ks o

f am

phot

eric

in B

ifFl

ucon

azol

e40

0-80

0 m

g da

ilyle

sions

clin

ical

ly s

tabl

e an

d im

prov

ed.

Inva

sive

Asp

ergi

llosi

sAs

perg

illus

fum

igat

usVo

rico

nazo

le6

mg/

kg IV

q12

h fir

st d

ay≥1

0 w

eeks

- Inf

ectio

us D

iseas

es c

onsu

lt re

com

men

ded.

Aspe

rgill

us fl

avus

then

4 m

g/kg

IV q

12h

- For

cen

tral

ner

vous

sys

tem

infe

ctio

n,O

ther

Asp

ergi

llus

spp

orth

en 2

00 m

g PO

bid

*vo

ricon

azol

e re

com

men

ded

and

ABL

C5

mg/

kg/d

IV≥1

0 w

eeks

***

neur

osur

gery

ofte

n re

quire

d.Sa

lvag

e***

***

Com

bina

tion

antif

unga

l the

rapy

may

Mic

afun

gin

100

mg

IV d

aily

≥10

wee

ksbe

nee

ded.

Con

sult

Infe

ctio

us D

iseas

es.

32-75 1/9/12, 3:04 PM61


Empiric Therapy of Fungal Infections (cont’d)In

fect

ion

Usu

al P

atho

gens

Reco

mm

ende

dRe

com

men

ded

Dos

eRe

com

men

ded

Dur

atio

nC

omm

ents

Empi

ric

Ther

apy

Fung

al S

inus

itis

Aspe

rgill

us s

ppIm

mun

ocom

pete

nt- I

n im

mun

ocom

pete

nt h

ost,

fung

i in

sinus

esAn

tifun

gal t

hera

py n

otm

ay b

e as

soci

ated

with

nas

al p

olyp

osis

and

rout

inel

y re

com

men

ded

do n

ot ro

utin

ely

requ

ire a

ntifu

ngal

ther

apy.

- In

imm

unoc

ompr

omise

d pa

tient

s/di

abet

icIm

mun

ocom

prom

ised

keto

acid

osis,

a fu

ngal

infe

ctio

n ca

n pr

esen

t as

Aspe

rgill

usas

a c

ellu

litis

that

may

rapi

dly

prog

ress

and

Vori

cona

zole

6 m

g/kg

IV q

12h

first

day

be fa

tal.

Surg

ical

deb

ridem

ent i

s ne

cess

ary.

then

4 m

g/kg

IV q

12h

or*

Use

the

high

er d

ose

if ne

utro

peni

c.20

0 m

g PO

bid

** O

ther

Azo

les

and

mic

afun

gin

not

orac

tive

agai

nst

Rhiz

opus

/Muc

or s

pp.

Am

phot

eric

in B

1-1.

25 m

g/kg

/d*

IV

Rhiz

opus

/Muc

or**

Am

phot

eric

in B

0.8-

1.5

mg/

kg/d

IVPo

saco

nazo

le (

NF)

200

mg

PO q

id

Ende

mic

Myc

oses

*C

rypt

ococ

cus

spp*

*- I

nfec

tious

Dise

ases

con

sult

stro

ngly

reco

mm

ende

d.H

istop

lasm

a sp

p***

* Th

erap

y/do

se/d

urat

ion

depe

nden

t on

clin

ical

pic

ture

.Bl

asto

myc

es s

pp**

Cas

pofu

ngin

not

act

ive

agai

nst C

rypt

ococ

cus

spp.

Coc

cidi

oide

s sp

p**

* Fl

ucon

azol

e le

ss e

ffect

ive

then

itra

cona

zole

aga

inst

Hist

opla

sma

spp.

32-75 1/9/12, 3:04 PM62


Immunization for AdultsChildhood immunization programs have proven to be an effective and safe method ofpreventing many infectious diseases. The delivery and implementation of adultimmunization programs have not matched the successes achieved in the pediatricpopulation. However given increased emphasis on disease prevention, healthcareproviders must be made aware of the need to improve immunization among adults.Immunization status should be considered an integral part of the health assessment of anyadult. Opportunities to provide vaccines to adults are being missed in the healthcaresetting. Prevention of infection by immunization is a lifelong process that should betailored to meet individual variations in risk resulting from age, illness, travel, occupationand lifestyle.

Canadian recommendations for vaccination can be found in the CanadianImmunization Guide, sixth edition 2006 or at http://phac-aspe.gc.ca/publicat/cig-gci/index.html or e-CPS-Clin-Info “vaccines”.

Opportunities for Immunization in Acute Care Institutions

A vaccination history taken on admission to hospital provides an important opportunityto ensure that up-to-date immunization is maintained in all individuals.

In acute care hospitals the admission of elderly patients and others at risk for complicationsfrom influenza and other diseases should be seen as opportunity to ensure protectionagainst these diseases. All routine vaccines should be up to date and consideration shouldbe given to other vaccines as needed.

(see next page for more information on individual vaccines, toxoids)

Opportunities for Immunization in Long-Term Health Care Facilities

Annual vaccination against influenza is strongly recommended for individuals in nursinghomes and chronic care institutions. Pneumococcal vaccine is recommended for theelderly and chronically ill, particularly in closed populations. A single dose should beadministered to all unvaccinated individual admitted to such facilities. All routine vaccinesshould be up to date and consideration should be give to other vaccines as needed.

(see next page for more information on individual vaccines, toxoids)

32-75 1/9/12, 3:04 PM63


Immunization for Adults (cont’d)Va

ccin

e or

Indi

cati

onTi

min

g C

omm

ents

toxo

id

Dip

hthe

ria

All a

dults

Ever

y 10

yea

rs, a

s Td

Adv

erse

eve

nts:

Tran

sient

loca

l and

febr

ile re

actio

ns (

usua

lly m

ild a

nd se

lf-lim

iting

)(I

M)

Con

trai

ndic

atio

ns: A

llerg

y to

any

com

pone

nt o

f the

vac

cine

Teta

nus

All a

dults

Ever

y 10

yea

rs, a

s Td

Adv

erse

eve

nts:

Loca

l ery

them

a an

d sw

ellin

g. Se

vere

loca

l rea

ctio

ns a

re a

ssoc

iate

d(I

M)

with

hig

h le

vels

of a

ntito

xin,

ofte

n as

a re

sult

of o

ver v

acci

natio

n C

ontr

aind

icat

ions

: Alle

rgy

to a

ny co

mpo

nent

of t

he v

acci

ne. N

o bo

oste

r dos

e in

the l

ast f

ive

yea

rs o

r 10

year

s if m

ajor

loca

l rea

ctio

n or

avo

id u

se a

t all

if pr

evio

us m

ajor

syst

emic

reac

tion

Pert

ussi

sAd

ults

who

hav

e not

Giv

e onc

e as d

Tap

(it is

Adv

erse

eve

nts:

Tran

sient

, loc

al p

ain,

eryt

hem

a an

d sw

ellin

g w

ere g

ener

ally

mild

prev

ious

ly re

ceiv

ed a

dos

ere

com

mem

ded

that

a si

ngle

Con

trai

ndic

atio

ns: H

yper

sens

itivi

ty to

any

com

pont

of t

he v

acci

neof

ace

llula

r Per

tuss

is va

ccin

eTd

boo

ster

be r

epla

ced

with

the c

ombi

ned

dTap

vac

cine

)

Infl

uenz

aAd

ults

>65

yrs

or <

65G

ive y

early

bet

wee

n C

ontr

aind

icat

ions

: Ana

phyl

axis

to eg

gs, p

revi

ous a

llerg

ic re

actio

n to

influ

enza

(IM

, SC

)yr

s with

chro

nic

Sept

embe

r and

vac

cine

med

ical

cond

ition

s1D

ecem

ber

Pneu

moc

occa

lAd

ults

>65

yrs

Onc

e in

a lif

e-tim

e A

dver

se e

vent

s: Lo

cal s

oren

ess a

nd er

ythe

ma

are c

omm

on(p

olys

acca

ride)

or <

65 y

rs w

ithRe

-vac

cina

tion

once

in C

ontr

aind

icat

ions

: Pre

viou

s alle

rgic

reac

tion

to p

neum

ococ

cal v

acci

ne(I

M, S

C)

chro

nic m

edic

al5

year

s for

the f

ollo

win

g:co

nditi

ons2

patie

nts w

ith a

sple

nia,

sickl

e cel

l dise

ase,

seve

reca

rdio

pulm

onar

y di

seas

e,ci

rrho

sis, c

hron

ic re

nal

failu

re, H

IV in

fect

ion,

or

imm

unos

uppr

essio

n

Mea

sles

All a

dults

bor

n in

197

0 or

All a

dults

bor

n in

197

0 or

Adv

erse

eve

nts:

Feve

r, tr

ansie

nt th

rom

bocy

tope

nia

and

very

rare

ly en

ceph

aliti

s(p

refe

rabl

e to

late

r who

are

susc

eptib

lela

ter w

ho a

re su

scep

tible

Con

trai

ndic

atio

ns: I

mm

unos

uppr

essio

n. P

revi

ous a

llerg

ic re

actio

n to

mea

sles o

r MM

R va

ccin

es,

give

as M

MR)

to m

easle

sto

mea

sles (

by se

rolo

gy)

neo

myc

in a

llerg

y(S

C)

Rube

llaSu

scep

tible

wom

en o

fO

ne d

ose,

no

furt

her

Adv

erse

eve

nts:

Rash

, lym

phad

enop

athy

, tra

nsie

nt a

rthr

algi

a(S

C)

child

bear

ing

age a

nddo

ses n

eede

d C

ontr

aind

icat

ions

: Pre

gnan

cy, i

mm

unos

uppr

essio

n, a

llerg

y to

neo

myc

inhe

alth

care

wor

kers

Mum

psAd

ults

bor

n in

One

dos

e, n

o fu

rthe

r A

dver

se e

vent

s: Fe

ver,

paro

titis,

rash

(SC

)19

70 o

r lat

erdo

ses n

eede

d C

ontr

aind

icat

ions

: Pre

gnan

cy, i

mm

unos

uppr

essio

n, a

llerg

y to

neo

myc

in

32-75 1/9/12, 3:04 PM64


Immunization for Adults (cont’d)

Vari

cella

Susc

eptib

le h

ealth

Two

dose

s sep

arat

edA

dver

se e

vent

s: Fe

ver,

loca

l rea

ctio

ns, r

ash

(SC

)ca

re w

orke

rs, a

ndby

4 to

8 w

eeks

Con

trai

ndic

atio

ns: H

yper

sens

itivi

ty to

any

vac

cine

com

pone

nt in

clud

ing

neom

ycin

, mal

igna

ntce

rtai

n pa

tient

neop

lasm

s affe

ctin

g th

e bon

e mar

row

, im

mun

osup

pres

sion,

act

ive u

ntre

ated

TB,

pre

gnan

cypo

pula

tions

4W

arni

ngs:

Avoi

d sa

licyl

ates

for 6

wee

ks

Hep

atit

is B

3O

ccup

atio

nal,

life-

styl

e or

Serie

s of t

hree

dos

esA

dver

se e

vent

s: Fe

ver,

loca

l rea

ctio

ns(I

M)

envi

ronm

enta

l exp

osur

e4C

ontr

aind

icat

ions

: Hyp

erse

nsiti

vity

to a

ny v

acci

ne co

mpo

nent

Hae

mop

hilu

s BPa

tient

s with

ana

tom

ic o

rO

ne d

ose

Adv

erse

eve

nts:

Feve

r, lo

cal r

eact

ions

(HIB

)fu

nctio

nal a

sple

nia

and

Cur

rent

ly n

oC

ontr

aind

icat

ions

: Hyp

erse

nsiti

vity

to a

ny v

acci

ne co

mpo

nent

(IM

)ot

her i

mm

unos

uppr

esse

dre

com

men

datio

ns fo

rpa

tient

s at r

isk fo

r inv

asiv

ere

vacc

inat

ion

are

HIB

infe

ctio

nav

aila

ble

Men

actr

aPa

tient

s with

ana

tom

icPa

tient

s with

ana

tom

ic o

rA

dver

se e

vent

s: Fe

ver,

loca

l rea

ctio

nsA

,C,Y

and

W-1

35or

func

tiona

l asp

leni

afu

nctio

nal a

sple

nia

Con

trai

ndic

atio

ns: H

yper

sens

itivi

ty to

any

vac

cine

com

pone

nt(c

onju

gate

) (IM

)Pr

efer

red

to g

ive d

ose

x 1

(inst

ead

of C

-con

juga

te fo

llow

ed b

y A,

C,

Y, W

-135

pol

ysac

char

ide)

Men

ingo

cocc

alPa

tient

s with

ana

tom

icO

ne d

ose (

2 w

eeks

aft

er co

njug

ate)

Adv

erse

eve

nts:

Feve

r, lo

cal r

eact

ions

A,C

,Y a

nd W

-135

or fu

nctio

nal a

sple

nia

The n

eed

for r

epea

t dos

es a

ndC

ontr

aind

icat

ions

: Hyp

erse

nsiti

vity

to a

ny v

acci

ne co

mpo

nent

(pol

ysac

char

ite)

thei

r opt

imal

tim

ing

is un

know

n(S

C)

(effe

ctiv

enes

s of v

acci

ne is

prob

ably

2 y

ears

or l

ess)

Men

ingo

cocc

alPa

tient

s with

ana

tom

icG

ive d

ose (

2 w

eeks

pri

or to

Adv

erse

eve

nts:

Feve

r, lo

cal r

eact

ions

C (c

onju

gate

) (IM

)or

func

tiona

l asp

leni

apo

lysa

ccha

ride v

acci

ne)

Con

trai

ndic

atio

ns: H

yper

sens

itivi

ty to

any

vac

cine

com

pone

nt

Hep

atit

is A

3O

ccup

atio

nal,

life-

styl

e or

Serie

s of t

wo

to th

ree d

oses

Adv

erse

eve

nts:

Feve

r, lo

cal r

eact

ions

(IM

)en

viro

nmen

tal e

xpos

ure4

(dep

endi

ng o

n th

e pro

duct

)C

ontr

aind

icat

ions

: Hyp

erse

nsiti

vity

to a

ny v

acci

ne co

mpo

nent

1. C

ardi

ores

pira

tory

dise

ase,

dia

bete

s mel

litus

, hep

atic

or r

enal

dise

ase,

canc

er, i

mm

unos

uppr

essio

n, a

lcoh

olism

, res

iden

ce in

an

inst

itutio

n2.

Car

dior

espi

rato

ry d

iseas

e (ex

cept

ast

hma)

, dia

bete

s mel

litus

, alc

ohol

ism, c

irrho

sis, r

enal

dise

ase,

canc

er, a

sple

nia,

sick

le ce

ll di

seas

e, C

SF le

ak, H

IV in

fect

ion,

hom

eles

snes

s, IV

DU

3. T

here

is co

mbi

natio

n H

epat

itis A

/B v

acci

ne a

vaila

ble

4. P

leas

e cal

l Pha

rmac

y or

refe

r to

Can

adia

n Im

mun

izat

ion

Gui

delin

e 7th ed

200

6 fo

r mor

e inf

orm

atio

n.

32-75 1/9/12, 3:04 PM65


Patient: Allergies:

PRE-PRINTED ORDERDepartment of Medicine, Infectious Diseases

Pneumonococcal & Influenza Vaccination

CD0880MR 10/05 Page 1 of 1Top copy – chart Bottom copy – pharmacy

Physician’s Signature: Date (YYYY/MM/DD):

Physician’s Name: CPSNS No.Print

THE FOLLOWING ORDERS:• May be used on any nursing unit and will be carried out by a qualified health professional ONLY ON THE

AUTHORITY OF A PHYSICIAN• All orders to be carried out must be checked/completed as appropriate. • All dates must be written yyyy/mm/dd. All times must be on the 24-hour clock (hhmm hr).

1. Risk assessment for INFLUENZA: At high risk due to: (check all applicable)a. ■ Age 65 or olderb. ■ Chronic cardiovascular or pulmonary disease (i.e. asthma*, COPD)c. ■ Resident in nursing homed. ■ Chronic condition such as diabetes mellitus, cancer, immunodeficiency, immunosuppression, renal

disease, anemia or hemoglobinopathye. ■ HIVf. ■ Foreign travel to destination where influenza is likely circulatingg. ■ Health care occupation or contact with people at high risk

2. Risk assessment for PNEUMONOCOCCAL disease: At high risk due to: (check all applicable)■ At risk for influenza (any of box a. through e. above checked; exception – box f. or g.)■ Asplenia, splenic dysfunction, sickle cell disease, cirrhosis, alcoholism or chronic leak of cerebrospinal fluid* Asthma alone has not been associated with increased risk for pneumococcal disease

3. Contraindications (check all applicable)■ Anaphylactic reaction to a previous dose■ Hypersensitivity to eggs (influenza only) or other components of the vaccine■ Acute febrile illness■ Previously received pneumococcal vaccine. [Some sub-groups require re-immunization (See Canadian

Immunization Guide)]

4. ■ Administer pneumococcal vaccine (0.5 mL intra-muscularly or subcutaneously in deltoid)

5. ■ Administer influenza vaccine [0.5 mL intramuscularly in deltoid (subcutaneously also permissible)]

6. ■ Do not administer vaccines

32-75 1/9/12, 3:04 PM66


Risk assessment for pneumococcal vaccine only (as all patients are at risk for influenza disease and qualify for vaccine

unless there is a contraindication)

Assess contraindications

Obtain Informed Consent

Discuss:

- Benefits of vaccine s)

- Risks of not getting vaccinated

- Common and expected side effects of the vaccine (s)

- Possible serious adverse effects and their frequency

- Potential need and consent for anaphylaxis management

- Provide opportunity for questions

- Patient appears to understand and knowingly consents

Administer vaccine(s)

Document administration of vaccine including lot number and site of injection(s) either in MAR

32-75 1/9/12, 3:04 PM67


Guidelines for the Empiric Treatment ofIntra-abdominal Infections

Infe

ctio

nPa

tien

t Cri

teri

aU

sual

Pat

hoge

ns R

ecom

men

ded

Alt

erna

tive

sD

urat

ion

Com

men

tsEm

piri

c Th

arpy

Acu

te C

hol

ecys

titi

sM

ildU

sual

ly d

oes n

ot re

quir

ean

tim

icro

bial

ther

apy

Mod

erat

e to

seve

reE.

coli

Cef

azol

in +

Peni

cilli

n-al

lerg

ic:

7-10

day

sa E

nter

ococ

cus s

houl

dB.

frag

ilis

met

roni

dazo

leb

Clin

dam

ycin

+be

trea

ted

only

ifEn

tero

cocc

usa

OR

gent

amic

inc

3-5

days

isola

ted

b Cef

oxiti

n is

Ampi

cilli

n +

OR

if no

inte

rcha

nged

toge

ntam

icin

c +C

ipro

floxa

cin

+pe

rfor

atio

n,ce

fazo

lin +

met

roni

dazo

lem

etro

nida

zole

met

roni

dazo

leab

cess

, or

c Am

inog

lyco

sides

shou

ldch

olan

gitis

be a

void

ed in

the e

lder

ly,

Ora

l Ste

pdow

n:O

ral S

tepd

own:

criti

cally

ill,

or th

ose

Amox

icill

in/

Cip

roflo

xaci

n +

with

rena

l im

pairm

ent.

clav

ulan

ate

met

roni

dazo

le

Acu

te C

hola

ngit

isU

ncom

plic

ated

E. co

liC

efaz

olin

+Pe

nici

llin-

alle

rgic

:10

day

sa E

nter

ococ

cus s

houl

d(n

o pe

rfor

atio

nB.

frag

ilis

met

roni

dazo

leb

Clin

dam

ycin

+be

trea

ted

only

ifor

abs

cess

)En

tero

cocc

usa

OR

gent

amic

inc

isola

ted

b Cef

oxiti

n is

Ampi

cilli

n +

OR

inte

rcha

nged

toge

ntam

icin

c +C

ipro

floxa

cin

+ce

fazo

lin +

met

roni

dazo

lem

etro

nida

zole

met

roni

dazo

lec A

min

ogly

cosid

es sh

ould

be a

void

ed in

the e

lder

ly,

Ora

l Ste

pdow

n:O

ral S

tepd

own:

criti

cally

ill,

or th

ose

Amox

icill

in/

Cip

roflo

xaci

n +

with

rena

l im

pairm

ent.

clav

ulan

ate

met

roni

dazo

le

Perf

orm

atio

n/ab

sces

sSe

e Sec

onda

ryPe

riton

itis

Post

-ERC

PP.

aer

ugin

osa

Pipe

raci

llin/

Peni

cilli

n-al

lerg

ic:

tazo

bact

amC

ipro

floxa

cin

+m

etro

nida

zole

* Cul

ture

s and

sens

itivi

ties s

houl

d al

way

s be u

sed

to gu

ide a

ntim

icro

bial

ther

apy w

hen

avai

labl

e

32-75 1/9/12, 3:04 PM68


Guidelines for the Empiric Treatment ofIntra-abdominal Infections (cont’d)

Infe

ctio

nPa

tien

t Cri

teri

aU

sual

Pat

hoge

ns R

ecom

men

ded

Alt

erna

tive

sD

urat

ion

Com

men

tsEm

piri

c Th

arpy

Acu

teM

ild-m

oder

ate

E. co

liO

ral T

her

apy:

bPe

nici

llin-

alle

rgic

:7-

10 d

ays,

a Onl

y am

oxic

illin

-D

iver

ticu

liti

sB.

frag

ilis

Amox

icill

in-c

lavu

lana

teC

ipro

floxa

cin

+ac

cord

ing

clav

ulan

ate c

over

sEn

tero

cocc

usa

OR

met

roni

dazo

leto

clin

ical

Ente

roco

ccus

Trim

etho

prim

/re

spon

se.

b Ora

l the

rapy

issu

lfam

etho

xazo

le +

appr

opria

te fo

r mild

met

roni

dazo

leun

com

plic

ated

IV T

hera

py:

infe

ctio

nsC

efaz

olin

+ m

etro

nida

zole

Seve

reSe

e Sec

onda

ry P

erito

nitis

Acu

te P

ancr

eati

tis

Com

plic

ated

-E.

coli

Pipe

raci

llin/

Peni

cilli

n-al

lerg

ic:

Dep

ende

ntTa

ilor a

ntim

irobi

als

absc

ess,

infe

cted

Ente

roco

ccus

spp

tazo

bact

amC

ipro

floxa

cin

+on

clin

ical

to C

&S r

esul

ts.

pseu

docy

st, i

nfec

ted

S. a

ureu

sO

Rm

etro

nida

zole

pict

ure,

necr

otic

pan

crea

sC

oagu

lase

Mer

open

emm

ay b

ene

gativ

e Sta

phpr

olon

ged.

Anae

robe

sC

andi

da sp

p

32-75 1/9/12, 3:04 PM69



Infe

ctio

nPa

tien

t Cri

teri

aU

sual

Pat

hoge

ns R

ecom

men

ded

Alt

erna

tive

sD

urat

ion

Com

men

tsEm

piri

c Th

arpy

Acu

te A

ppen

dici

tis

Unc

ompl

icat

edEm

piri

c th

erap

yn

ot re

quir

ed

Com

plic

ated

(gan

gren

e,pe

rfor

atio

n,ab

sces

s or

perit

ioni

tis)

See S

econ

dary

Perit

oniti

s

Live

r Abs

cess

Bact

eria

lE.

coli

Dra

inag

e and

:Pi

pera

cilli

n/4

wee

ks o

rB.

frag

ilis

Cef

azol

in +

tazo

bact

amun

til C

TEn

tero

cocc

usm

etro

nida

zole

reso

lutio

nSt

rept

ococ

cus

Peni

cilli

n-al

lerg

ic:

angi

nosu

s/O

ral S

tepd

own:

Cip

roflo

xaci

n +

mill

eri g

roup

Amox

icill

in/c

lavu

lana

tem

etro

nida

zole

Spon

tane

ous

Ente

roba

cter

iace

aeC

efot

axim

ePe

nici

llin-

alle

rgic

:10

-14

days

Bact

eria

lS.

pne

umon

iae

Cip

roflo

xaci

nPe

rito

niti

sSt

rept

ococ

cus s

ppO

ral S

tepd

own:

Amox

icill

in/c

lavu

lana

teO

ral S

tepd

own:

Cip

roflo

xaci

n

32-75 1/9/12, 3:04 PM70



Infe

ctio

nPa

tien

t Cri

teri

aU

sual

Pat

hoge

ns R

ecom

men

ded

Alt

erna

tive

sD

urat

ion

Com

men

tsEm

piri

c Th

arpy

Seco

nda

ryC

omm

unity

-E.

coli

Ampi

cilli

n +

Cef

tria

xone

e +

Dep

ende

nta T

reat

if is

olat

ed.

Peri

toni

tis

acqu

ired

B. fr

agili

sge

ntam

icin

b +m

etro

nida

zole

on cl

inic

ala A

min

ogly

cosid

es sh

ould

(e.g

. bow

elEn

tero

cocc

usm

etro

nida

zole

pict

ure

be a

void

ed in

the e

lder

ly,

perf

orat

ion,

Stre

ptoc

occu

s spp

OR

Peni

cilli

n-al

lerg

ic:

criti

call

ill, o

r tho

se w

ithru

ptur

edC

andi

da sp

paC

efaz

olin

+C

linda

myc

in +

rena

l im

pairm

ent.

appe

ndix

)m

etro

nida

zole

cge

ntam

icin

ac C

efox

itin

is in

terc

hang

ed to

OR

cefa

zolin

+ m

etro

nida

zole

.O

ral S

tepd

own:

dC

ipro

floxa

cin

+d O

ral s

tepd

own

appr

opria

teAm

oxic

illin

/m

etro

nida

zole

in p

atie

nts w

ith a

wor

king

clav

ulan

ate

GI t

ract

and

nor

mal

izin

gO

ral S

tepd

own:

dW

BC a

nd te

mp.

*Cip

roflo

xaci

n +

e Hig

h in

cide

nce o

f dia

rrhe

am

etro

nida

zole

and

bilia

ry sl

udgi

ng.

f Tre

at w

ith a

diff

eren

tH

ospi

tal-a

cqui

red

E. co

liC

efaz

olin

+Pi

pera

cilli

n/D

epen

dent

antim

icro

bial

clas

s and

and

no p

revi

ous

B. fr

agili

sm

etro

nida

zole

bta

zoba

ctam

on cl

inic

alco

nsid

er In

fect

ious

antim

icro

bial

Ente

roco

ccus

spp

pict

ure

Dise

ases

cons

ult.

ther

apy,

or i

ntra

-Kl

ebsie

lla sp

pPe

nici

llin-

alle

rgic

:ab

dom

inal

abs

cess

Prot

eus s

ppC

ipro

floxa

cin

+P.

aer

ugin

osa

met

roni

dazo

leC

andi

da sp

p

Hos

pita

l-acq

uire

d,E.

coli

Pipe

raci

llin/

Mer

open

emD

epen

dent

prev

ious

ant

imic

robi

alB.

frag

ilis

tazo

bact

amon

clin

ical

ther

apyf , o

r IC

UEn

tero

cocc

us sp

pPe

nici

llin-

alle

rgic

:pi

ctur

ead

miss

ion

Kleb

siella

spp

*Cip

roflo

xaci

n +

Prot

eus s

ppm

etro

nida

zole

P. a

erug

inos

aSe

rrat

ia sp

pAc

inet

obac

ter s

ppS.

epid

erm

isC

andi

da sp

pa

*Cip

roflo

xaci

n +

met

roni

dazo

le d

oes n

ot co

ver e

nter

ococ

cus

32-75 1/9/12, 3:04 PM71



Infe

ctio

nPa

tien

t Cri

teri

aU

sual

Pat

hoge

ns R

ecom

men

ded

Alt

erna

tive

sD

urat

ion

Com

men

tsEm

piri

c Th

arpy

Tert

iary

P. a

erug

inos

aTr

eat a

ccor

ding

Con

tinue

a Tre

at if

isol

ated

.Pe

rito

nit

isE.

faec

ium

to C

&S r

esul

tsun

til a

febr

ile,

Coa

gula

seno

rmal

WBC

/ne

gativ

e Sta

phdi

ffere

ntia

l,C

andi

da sp

pano

resid

ual

fluid

colle

ctio

ns,

depe

nden

t on

the c

linic

alpi

ctur

e.

Refe

renc

es a

vaila

ble u

pon

requ

est f

rom

Pha

rmac

y.

32-75 1/9/12, 3:04 PM72


Pelvic Inflammatory DiseaseEt

iolo

gies

Trea

tmen

tSu

gges

ted

Regi

men

s

Alte

rnat

ive

Regi

men

sIn

patie

ntN

ote:

Hos

pita

lizat

ion

Crit

eria

: pre

gnan

cy, w

hen

surg

ical

em

erge

ncie

s (i.

e., a

ppen

dici

tis) a

re n

ot e

xclu

ded,

pat

ient

not

resp

ondi

ng c

linic

ally

toor

al th

erap

y, p

atie

nt n

ot a

ble

to fo

llow

or t

oler

ate

outp

atie

nt re

gim

ens,

sev

ere

illne

ss, n

ause

a an

d vo

miti

ng, h

igh

feve

r, or

tubo

-ova

rian

absc

ess.

Con

sider

hos

pita

lizat

ion

for o

ral o

r par

ente

ral t

hera

py in

HIV

infe

cted

pat

ient

s or

you

th/a

dole

scen

ts.

Sexu

ally

Tra

nsm

itted

:C

hlam

ydia

trac

hom

atis

Nei

sser

ia g

onor

rhoe

aeH

erpe

s sim

plex

viru

sTr

icho

mon

as v

agin

alis

Endo

geno

us o

rgan

isms:

Myc

opla

sma

geni

taliu

mM

ycop

lasm

a ho

min

isU

reap

lasm

a ur

ealy

ticum

Anae

robi

c ba

cter

ia:

Bact

eroi

des

spp.

Out

patie

ntPe

ptos

trep

toco

ccus

spp

.Pr

evot

ella

spp

.Fa

culta

tive

(aer

obic

) bac

teria

:Es

cher

ichi

a co

liG

ardn

erel

la v

agin

alis

Hae

mop

hilu

s in

fluen

zae

Stre

ptoc

occu

s sp

p.

Mos

t cas

es a

re a

ssoc

iate

dw

ith m

ore

than

one

org

anism

• *M

ost e

xper

ts re

com

men

d do

xycy

clin

e ca

n be

adm

inist

ered

ora

lly in

hos

pita

lized

pat

ient

s du

e to

pai

nful

and

cos

tly IV

adm

inist

ratio

n. O

ral a

nd IV

adm

inist

ratio

nal

so h

ave

simila

r bio

avai

labi

lity.

• Ef

ficac

y an

d co

mpl

icat

ion

rate

s ar

e no

t sig

nific

antly

diff

eren

t bet

wee

n pa

rent

eral

ver

sus

oral

ther

apy

or in

patie

nt v

ersu

s ou

tpat

ient

trea

tmen

t.•

If pa

tient

doe

s no

t rec

over

, con

sider

diff

eren

tial d

iagn

osis

and

lapa

rosc

opy.

• Im

prov

emen

t in

pain

and

tend

erne

ss fr

om a

cute

PID

sho

uld

begi

n w

ithin

2-3

day

s af

ter i

nitia

ting

ther

apy.

Refe

renc

e: W

ong

T, e

dito

r. C

anad

ian

guid

elin

es o

n se

xual

ly tr

ansm

itted

infe

ctio

ns. O

ttaw

a: P

ublic

Hea

lth A

genc

y of

Can

ada;

200

8.

A)

Oflo

xaci

n 40

0 m

g IV

q12

h ±

met

roni

dazo

le 5

00 m

g IV

q12h

B) L

evof

loxa

cin

500

mg

IV q

24h

± m

etro

nida

zole

500

mg

IV q

12h

C)

Erta

pene

m 1

g IV

eve

ry 2

4 h

+ do

xycy

clin

e 10

0 m

g IV

or P

O*

ever

y 12

hN

ote:

Due

to c

once

rns

of a

naer

obic

cov

erag

e of

quin

olon

es, m

etro

nida

zole

sho

uld

be a

dded

to q

uino

lone

regi

men

s

A)

Oflo

xaci

n 40

0 m

g PO

BID

x 1

4 d

± m

etro

nida

zole

500

mg

PO B

ID fo

r 14

dB)

Lev

oflo

xaci

n 50

0 m

g PO

QD

± m

etro

nida

zole

500

mg

PO B

ID x

14

d

Patie

nts

with

con

trai

ndic

atio

ns to

cep

halo

spor

ins

orqu

inol

ones

can

be

trea

ted

with

azi

thro

myc

in 2

50 m

g PO

once

dai

ly x

7 d

or 1

g P

O w

eekl

y x

2 w

eeks

+ o

ral

met

roni

dazo

le

Not

e: Q

uino

lone

s ar

e co

nsid

ered

as

an a

ltern

ativ

e on

ly if

susc

eptib

ility

test

ing

is av

aila

ble

and

has

dem

onst

rate

dsu

scep

tibili

ty o

r a te

st o

f cur

e ca

n be

com

plet

ed.

A)

Cef

tria

xone

1 g

IV q

24h

+ do

xycy

clin

e 10

0 m

g IV

or

PO*

q12h

. IV

ther

apy

can

be d

iscon

tinue

d 24

h a

fter c

linic

alim

prov

emen

t, an

d do

xycy

clin

e 10

0 m

g BI

D P

O s

houl

dco

ntin

ue fo

r a to

tal o

f 14

days

of t

reat

men

t.B)

Clin

dam

ycin

900

mg

IV q

8h +

gen

tam

icin

6 m

g/kg

IVq2

4h. I

V th

erap

y ca

n be

disc

ontin

ued

24 h

afte

r clin

ical

impr

ovem

ent,

and

doxy

cycl

ine

100

mg

BID

PO

or

clin

dam

ycin

450

mg

QID

PO

sho

uld

cont

inue

for a

tota

l of

14 d

ays

of tr

eatm

ent.

A)

Cef

tria

xone

250

mg

IM s

ingl

e do

se +

dox

ycyc

line

100

mg

BID

PO

x 1

4 d

B) O

ther

par

ente

ral 3

rd g

ener

atio

n ce

phal

ospo

rin

(i.e

.,ce

fota

xim

e) +

dox

ycyc

line

100

mg

PO B

ID x

14

d.

(Met

roni

dazo

le 5

00 m

g PO

BID

x 1

4 d

may

be

adde

d to

thes

e re

gim

ens

for m

ore

anae

robi

c co

vera

ge)

32-75 1/9/12, 3:04 PM73


Penicillin Allergy – An OverviewClinical situations for which penicillin is indicated as the sole effective treatment arise frequently inhospital practice. The evaluation of suspected penicillin allergy is therefore essential in makingdecisions about alternative antibiotic therapy verses penicillin. Up to 20% of hospitalizedindividuals claim allergy to penicillin. However, penicillin can also cause non-allergic intolerance(most commonly manifested as GI effects) and it is this intolerance that is often misinterpreted asallergy by many patients. Other reasons for misdiagnosis of penicillin allergy may include apatient’s faulty recall or natural declining hypersensitivity over time. Three to seven percent ofpatients taking ampicillin or amoxicillin develop maculopapular rashes. These rashes are not IgE-mediated however, and develop more commonly (up to 100%) in a patient with mononucleosisor with concurrent allopurinol therapy (up to 30%).

After a careful review of past penicillin usage and subsequent outcomes, all patients withsuspected allergies can be classified into one of three categories represented in the following table:

• Those patients found to be “Allergic” should avoid penicillins.

• There is less chance of a serious reaction in the “Possibly Allergic” category becausethese symptoms are consistent with reactions to the drug’s primary metabolites, notminor determinants, and are less likely to result in anaphylaxis.

• An “Allergy Not Likely” patient implies that the effects previously experienced, areGI or infusion-related and not allergy-related; penicillin and related drugs may beconsidered.

• Patients with chronic urticaria may have urticaria exacerbated by any antimicrobialsor infection - patient can be referred to Immunology.

ALLERGY NOT LIKELY

• Nausea, vomiting,diarrhea

• Negative rechallenge• Injection site reactions:

pain, phlebitis• Seizures• Unknown reaction

ALLERGIC

• Anaphylactic reactions: IgEswelling of throat, lips, orface; difficulty breathing,wheezing; urticaria

• Serum Sickness• Stevens-Johnson

POSSIBLY ALLERGIC

• Mild skin rash• Itchiness alone without

rash• Unknown reaction

32-75 1/9/12, 3:04 PM74

UPDATED

Feb 20

19


Reaction to any penicillin

History of urticarial rash, History of other type of reactionangioedema,bronchospasm,or hypotension Challenge with a penicillin,

cephalosporin*, or carbapenem**

Do penicillin skin test before giving any penicillin(consult Immunology) consider cephalosporin*,consider carbapenem **, or other class of antibiotics

Positive skin test result Negative skin test result

Avoid penicillins or Challenge with a penicillindesensitize patient (see PPO)

*In the general population, the risk of serious allergic reactions to cephalosporins appears to be<0.02%; the risk is lowest for third-generation cephalosporins (possibly because free drugcompetes with bound drug for antibodies to the side chain). Therefore, even if patients with ahistory of penicillin allergy have twice as great a risk of have a serious reaction to cephalosporinsthat do control subjects; this risk may be lower than the risk that they will have a serious reactionto any alternative antibiotic.1

**Patients with a history of a reported or documented penicillin allergy appeared todemonstrate an 11% incidence of hypersensitivity when treated with a carbapenem, comparedwith an incidence of 2.7% for patients without a reported history of penicillin allergy.2 However,it is important to note these statistics are based on a variety of reaction severities, and lower rateshave been observed in other studies (1.5-5%)4,5

References1. Robinson, J.L., Hameed, T. and Carr S. Practical Aspects of Choosing an Antibiotic for Patients with a Reported Allergy to an

Antibiotic. CID 2002;35:26-31.2. Prescott W.A. et al. Incidence of Carbapenem-Associated Allergic-Type Reactions among Patients with versus Patients

without a Reported Penicillin Allergy. CID 2004;38:1102-1107.3. Romano, A. et al. Cross-Reactivity and Tolerability of Cephalosporins in Patients with Immediate Hypersensitivity to

Penicillins. Ann Intern Med. 2004;141:16-22.4. Schiavino, D. Cross reactivity and tolerability of imipenem Allergy 2009;64:1644.5. Atanaskovic M. Tolerability of imipenem in children with IgE mediated hypersentivity to penicilin Allergy 2008;63:237.

Penicillin Allergy (cont’d)

➝

➝

➝

➝➝ ➝

➝

➝

32-75 1/9/12, 3:04 PM75

UPDATED

Feb 20

19


76-85 1/9/12, 3:15 PM76

UPDATED


Pentamidine–Suggested Dosing GuidelinesPentamidine Therapy:

Pentamidine, 3-4 mg/kg/d IV as a single daily dose, infused over at least 1 hour (preferablyover 2-3 hours).

Side Effects of Pentamidine Therapy:

The use of injectable pentamidine is associated with a variety of serious adverse effects inapproximately 50% of treated patients. Medical staff should be consulted when abnormalitiesin laboratory data occur or if questions concerning change in management arise.

Side Effect Incidence (%)

Skin rash or thrombophlebitis 1–2

Hypotension (positioning patient in asupine position during administrationmay decrease incidence) 9 – 10

Arrhythmias (ventricular tachycardia) 1 – 2

Hypoglycemia, usually after first5-7 days of treatment 6 – 40

Hyperglycemia may occur up to monthsafter treatment, in about 5% of patientswith a history of hypoglycemia

Hypocalcemia 1 – 2

Myelotoxicity, neutropenia, pancytopenia 14 – 15

Nephrotoxicity, possibly progressing toacute renal failure including hyperkalemia,hypomagnesemia 23 – 25

Acute Pancreatitis rare, but serious

Elevated Liver Enzymes 9 – 11

Management of Pentamidine Therapy:• prior to therapy and daily: glucose (by chemstrip or blood) anytime of the day.• prior to therapy and twice weekly: CBC with differential and platelets; calcium,

magnesium; liver function tests; urea, creatinine, electrolytes.• vitals: beginning, and at end of infusion. Ambulatory patients should have BP checked

sitting at the completion of infusion to check for postural hypotension.• assure adequate fluid status before administering pentamidine, preloading with 500

mL of NaCL 0.9% may decrease the incidence of nephrotoxicity/hypotension.• avoid other nephrotoxic drugs (amphotericin B, aminoglycosides, vancomycin)

whenever possible.• counsel patient on signs and symptoms of acute pancreatitis i.e. acute abdominal pain,

nausea and vomiting.

76-85 1/9/12, 3:15 PM77


Empiric Therapy of PneumoniaEMPIRIC ANTIBIOTIC THERAPY OF PNEUMONIA IS DETERMINEDBY THREE MAIN FACTORS:

1. Where was the infection acquired?• Community vs Chronic Care Facility vs Acute Care Hospital vs Intensive Care Unit.

2. What are the patient’s age and underlying conditions?• Alcoholism, COPD, chronic bronchitis, altered level of consciousness or impaired

swallowing, influenza, chronic debilitating conditions (malignancy, chronic renalfailure, etc.), cystic fibrosis.

3. What is the severity of the illness?• Respiratory function (blood gases, need for ventilatory support, degree of distress).

• Progression of the illness (stable vs deteriorating).

An assessment of the first two factors will help determine the most likely pathogen.Empiric therapy should be initiated based on the above factors pending results of Gramstain and cultures. Therapy must be modified to the most effective and least costly therapy,once culture results are known.

The greatest cost savings are achieved by an early switch from intravenous to oral therapy.See Sequential Antibiotic Therapy and Pharmacist Initiation Route of AdministrationTherapeutic Interchange.

The following guidelines will assist in selecting the most cost-effective empiric therapy formost clinical situations.

76-85 1/9/12, 3:15 PM78


Suggested Guidelines for the Treatment ofCommunity-Acquired Pneumonia

Patient with community acquired pneumonia

CXR, CBC, lytes, urea, glucose,O2 sat (if <90% ABG)

Pneumonia severity scoring system

≤ 70 points 71-90 points ≥ 91 point

Fits extra dischargecriteria

1st dose IV/PO antibiotic inemergency dept.

Admit tohospital

Admit tohospital

1. D/C home2. Suggested antibiotic choices:

- Clarithromycin 500 mg po bid x 10 days- Azithromycin 500 mg po once then 250 mg po od x 4

days- Pts >65yrs can use Cefuroxime 500 mg po BID(↓ likelihood mycoplasma, chlamydia pneumoniae)

3. All patients should follow-up with their Family Physician4. Follow-up CXR if:

- Patient ≥55yrs old- Patient ≥45yrs old and smokes

5. Pneumonia education booklet

OrganismsNo Comorbidity Comorbidity

S.pneumoniae Legionella species S.pneumoniae S.aureusH.Influenzae Mycoplasma pneumoniae H.influenzae Gram-negative rodsS.aureus Chlamydia pneumoniae Oral anaerobes Legionella species

Extra Discharge Criteria

1.The patient’s O2 sat >90% on R/A (or if COPD paO

2>55) yes or no

2. Will the patient tolerate oral medications? yes or no3. Will the patient likely be compliant? yes or no4. Are home supports sufficient? yes or no

If you have answered NO to any of these questions, consider admission.

Start drugtherapy

No Yes

Start drugtherapy

➝➝

➝

➝

➝

➝

➝ ➝➝➝ ➝

➝

➝➝

➝

76-85 1/9/12, 3:15 PM79

OUTDATED


Treatment of Community-AcquiredPneumonia (cont’d)

Drug Therapy* Levofloxacin 500 mg IV/PO Once daily*

OR

* Ceftriaxone 1 g IV once daily + Azithromycin 500 mg IV/PO Once daily

* If patient has received a fluoroquinolone in the past 3 months, then choose an antibiotic fromanother class.

76-85 1/9/12, 3:15 PM80

OUTDATED


Suggested Guidelines for the Managementof Hospital-Acquired Pneumonia1,2,3

DefinitionsHospital-acquired pneumonia (HAP): Pneumonia that occurs 48 hours or more afteradmission, which was not incubating at the time of admission.

Diagnosis

Common Causative Pathogens:• Gram negative rods: Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae,

Proteus species, Enterobacter species, Serratia marcescens, Pseudomonas aeruginosa andAcinetobacter species.

• Gram positive cocci: Staphylococcus aureus, Streptococcus pneumoniae.

• Anaerobes: May play a role when there has been macroaspiration.

Clinical Strategy:• Diagnostic investigations (sputum and blood cultures) should be obtained prior to

antibiotic initiation or change.

TABLE 2Centers for Disease Control and Prevention criteria for nosocomial pneumonia

Pneumonia must meet one of the criteria (only in patients >12 months of age)

1. Rales or dullness to percussion on physical examination of chest and any of the following:• new onset of purulent sputum or change in character of sputum;• organism isolated from blood culture;• isolation of pathogen from specimen obtained by transtracheal aspirate, bronchial

brushing or biopsy.

2. Chest radiographic examination shows new or progressive infiltrate, consolidation,cavitation or pleural effusion and any of the following:• new onset of purulent sputum or change in character of sputum;• organism isolated from blood culture;• isolation of pathogen from specimen obtained by transtracheal aspirate, bronchial

brushing or biopsy;• isolation of virus or detection of viral antigen in respiratory secretions;• diagnostic single antibody titre (IgM) or four-fold increase in paired serum samples (IgG)

for pathogen.

Ig Immunoglobulin. Adapted from reference 3.

76-85 1/9/12, 3:15 PM81


Treatment

Empiric Therapy:• The treatment of HAP is usually empirical. Studies have shown that delayed or

inappropriate administration of empiric antimicrobial therapy is associated withincreased mortality. Therefore it is imperative that optimal treatment be initiated assoon as possible.

• Choice of agent should be based on our local patterns of susceptibility, anticipated sideeffects, and what antibiotics the patient has recently received, striving not to repeat thesame antimicrobial class if possible.

• Intravenous therapy should be used in all patients initially. A switch to oral/enteraltherapy can be made in patients with good clinical response and functioninggastrointestinal tract.

• Legionnaires’ Disease

• Legionella pneumophila should be suspected in severe or rapidly progressingpneumonia. Sputum for Legionella culture should be specifically requested in thissituation.

• Patients with suspected or diagnosed legionnaires’ disease should be treated with IVazithromycin, or a fluoroquinolone.

Ward patient (No risk factors for multi-drug resistant (MDR) pathogens*):• Initial Treatment: Ceftriaxone

• Stepdown: Amoxicillin/clavulanic acid, cefuroxime, or ciprofloxacin

*Risk factors for MDR pathogens:

(Antibiotic therapy should be tailored to reflect individual patient’s risk factors.)

• Current hospitalisation of 4 days or more;

• Antimicrobial therapy in preceding 30 days;

• Patients hospitalized in an acute care hospital for 2 or more days within 90 days of theinfection;

• Recent ICU admissions.

De-escalation:• Clinical improvement usually takes 48–72 hours, and thus therapy should not be

changed during this time unless there is rapid clinical decline.

• Broad spectrum empiric antibiotic therapy should be accompanied by a commitmentto streamline antibiotics, on the basis of clinical microbiologic data, to limit theemergence of resistance in the hospital and the potential for adverse effects.

Duration of Therapy:• If patients receive an initially appropriate antibiotic regimen, duration of therapy may

be shortened from 10-14 days to as short as 7 days, provided that the pathogen is not P.aeruginosa, S aureus and that the patient has a good clinical response with resolutionof clinical features of infection.

References:1. Am J Respir Crit Care Med 2005;171:388-4162. Microbiology Susceptibility Reports 2000, Antimicrobial Handbook, QEII3. Can J Infec Dis Med Micro January 2008; 19 (1): 19.

76-85 1/9/12, 3:15 PM82


Diagnostic algorithm for hospital-acquired pneumonia and ventilator-associated pneumonia.Please note that there is no definitive scientific evidence or expert consensus that quantitativetesting produces better clinical outcomes than empirical treatment. Scientific evidence ofimproved specificity, supplemented by expert opinion, supports the performance of invasivetests to avoid the use of antibiotics for clinically insignificant organisms, but there is no directevidence or consensus regarding the superiority of one invasive test over another. Factors toconsider in choosing an appropriate test include sensitivity and specificity, ability to improvepatient outcome, potential adverse effects, test availability and cost. CPIS Clinical pulmonaryinfection score; ICU Intensive care unit; PaO2 Partial pressure of oxygen in arterial blood.3

YES

YES

YES

YES

YES

YES

YES

YES

YES

NO

NO

NO

NO

NO NO

NO

Treat basedon Gram stain

and localepidemiology

Screen patient for clinical features: Does patient have two or more of the following features that aresuggestive of an infection?

a. temperature >38°C or <36°Cb. leukopenia/leukocytosisc. purulent tracheal secretionsd. decreased PaO2

Order chest x-ray

Review patient’s chest x-ray: Were any of the abnormalities listed below observedon the patient’s chest x-ray?

a. evidence of alveolar infiltratesb. evidence of air bronchogramsc. new or worsened infiltrates

Is the patient in the ICU?

Is the patient mechanically ventilated?

Calculate patient’s CPIS

Is the CPIS ≤6? Is the CPIS ≤6?

Stoptherapy ifstarted

Is the CPIS <4?

Initiate therapy

RecalculateCPIS daily

Stop therapyif CPIS ≤6on day 3

Continuetherapy ifCPIS >6on day 3

No further investigation is required;however, it is recommended that thepatient be monitored for any changes

to their condition

Recommended that the patient bemonitored and that an investigation into

other possible causes be conducted

Calculate patient’s CPIS

Are trachobronchialsecretions available

for Gram stain?

Are pus cells andorganisms present?

Diagnostic Algorithm HAP/VAP

76-85 1/9/12, 3:15 PM83


Treatment Guidelines for the Managementof Ventilator-Associated Pneumonia

SummaryPrompt appropriate therapy for critically ill patients with VAP and other infections reducesmortality. However, antibiotic resistant organisms are an increasing threat to the healthcare system. Within the hospital environment, critical care areas have the highestincidence of antibiotic resistant organisms.1 It is important therefore, to minimize the useof antibiotics whenever possible. This must be balanced with the fact that promptadequate therapy for critically ill patients with VAP affects clinical outcome.2

Developing this approach to the management of VAP was based on the followingpoints from the literature:

1. Mortality is lower in patients who initially receive the correct antimicrobial fortheir pneumonia, as shown in a number of studies.3-6 Initial treatment should bebased on local flora and antibiotic susceptibility patterns, the duration of priorhospital and ICU stay (“early” or “late”), and history of previous antibiotictherapy.7

2. There is to date no “gold standard” for the diagnosis of VAP. Clinical criteria fordiagnosing VAP are not very specific and often patients have non-infectiouscauses of their pulmonary infiltrates.9,10 As a result, antibiotics may be prescribedunnecessarily, with the potential for increased costs, adverse effects, and thefuture development of infection with resistant organisms.11 Prior receipt ofantibiotics is a risk factor for infection with resistant organisms in studies ofVAP. Bacteriological sampling is usually required to confirm clinically suspectedpneumonia and direct therapy.

3. Although not consistently done, various studies have shown that antibiotics cansafely be stopped in patients with negative bronchoscopic specimencultures.11,14,15

4. In selected patients with VAP, a 7 or 8 day course of treatment is as effective aslonger courses, and does not result in adverse patient outcomes.16,17

5. A comprehensive evaluation or algorithmic approach to VAP incorporatingformal reassessment of the need or tailoring of antibiotic therapy based onculture results, results in decreased antibiotic use, a decreased length of ICU stay,and a decreased rate of secondary infections.11,18

ConclusionThe optimization of the management of VAP (i.e. improved diagnosis, prompt, adequateinitiation of antibiotics, reassessment or narrowing of antibiotic therapy based on culturesand shorter duration of therapy) should lead to improved patient outcomes and adecreased risk of antibiotic resistance.

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CDHA Algorithum for the Diagnosis andManagement of VAP

InfectionSuspected

➝

VAP Criteria: New pulmonary infiltrate after 48hrs of intubation, not otherwise explainable,with at least one of: T >38oC,↑ WBC and two ormore of: new change in sputum purulence orvolume, rales or bronchial breath sounds,worsening gas exchange

PneumoniaDiagnosed

Draw Cultures: Blood andpulmonary secretions forculture should be sent on

every patient with VAP

START ANTIBIOTICS: Early(≤4 days in hosp): cefotaxime;Late (>4 days in hosp): pip/tazo or cipro + cefazolin; ifprev abx course: pip/tazo orceftazidime with either an AGor cipro

Adjust abxbased on C&S#

D/C Abx

Pathogen isolated Cultures Negative, and no abxwithin 72 hrs of specimen

Check culture resultsin 48-72 hours

* If tracheal aspirate cultures performed, use CPIS (who is going to do this; can we do this regularly whenVAP suspected?) score and re-evaluate after cultures available; D/C abx if CPIS ≤ 6# change to narrowest spectrum agent which will adequately cover organism; use 2 agents for Pseudomonasaeruginosa; for Serratia, Acinetobacter, Citrobacter or Enterobacter, use septra or cipro, or change topiperacillin + gentamicin

Can J Infect Dis Med Micro Apr 2007; 19(1): 19

D/C abx after8 days

Continue or adjustabx; look for

alternate source ofinfectionTreat for 10-14 days,

or 3 days afterclinical

improvement

Patient respondingclinically, initial abxcovered organism(s)

Pseudomonas, Acinetobacter,S.aureus, or initial abx didnot cover pathogen

Cultures Negative; pt hadsevere sepsis &/or abxprior to obtaining culture

➝

➝➝

➝➝

➝➝ ➝

➝

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SEPSISSuspectSEVERE SEPSIS or SEPTIC SHOCK

Suspect Severe Sepsis Or Septic Shock In A Patient Who Has:

1. A suspected infection (bacterial, fungal or viral)

2. Two or more vital sign abnormalities*

3. A lactate equal to or greater than 4 mmol/L and/or MAPless than 55 mmHg after a 2 L bolus

*Vital Sign Abnormalities

a) Temp less than 36°C or greater than

38°C

b) HR greater than 90 BPM

c) RR greater than 20 or PaCO2 less than32

d) WBC less than 4x109/L or greater than

12x109/L, or greater than 10% bands

Evidence of Organ Dysfunction:

1. Lactate equal to or greater than 4

2. Alteration in level of consciousness

3. Urine less than 0.5 mL/kg/h x 6h or increased creatinine 1.5 x baseline

4. Elevation of AST, ALT

Empiric Antibiotic Therapy For Patients With Suspected Severe Sepsis Or Septic Shock

Note: Every effort should be made to ensure that antibiotics are administered WITHIN 1 HOUR of the diagnosis of severe sepsis or

septic shock

If possible, obtain appropriate cultures prior to antibiotic administration; however, DO NOT DELAY ANTIBIOTICS FORCULTURES

Sepsis Origin Empiric Initial Intravenous Antibiotic

Unknown Vancomycin 20 mg/kg IV AND piperacillin/tazobactam 3.375 g IV

Lung (pneumonia)

A) Community Acquired / Nursing Home cefTRIAXone 1 g IV AND azithromycin 500 mg IV OR

levofloxacin 750 mg IV

B) Hospital Acquired piperacillin/tazobactam 3.375 g IV

**If MRSA suspected (homeless/incarceration/IV druguse)

ADD vancomycin 20 mg/kg IV

Intra-abdominal piperacillin/tazobactam 3.375 g IV

Urologic ampicillin 2 g IV AND gentamicin 4 mg/kg IV

Skin (rapidly progressing/necrotizing fasciitis) cefTRIAXone 1 g IV AND clindamycin 900 mg IV

Central Nervous System cefTRIAXone 2 g IV AND vancomycin 20 mg/kg IV

**ADD dexamethasone 10 mg IV before antibiotic

Febrile Neutropenia piperacillin/tazobactam 3.375 g IV

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PRE-PRINTED ORDER

Severe Sepsis / Septic Shock Resuscitation Patient: Allergies:

PPO0365MR_11_06 Jul 05 2011 Original chart page 1 of 1

Prescriber Date (yyyy/mm/dd):

Presc Name Reg. No. Print

1. Intravenous Fluid Resuscitation

Insert 2 large bore peripheral IV cannulas (#16 and #18 gauge)

Administer 1 L 0.9% sodium chloride IV rapid infusion over 15 30 min IMMEDIATELY

After 1 L 0.9% sodium chloride, if MAP is equal to or less than 55 mmHg, then repeat 1 L 0.9% sodium chloride IV infusion over 15 30 min IMMEDIATELY

After 2 L 0.9% sodium chloride, if MAP is still equal to or less than 55 mmHg and/or the patient has evidence of organ dysfunction (see reverse), physician to assess need for:

repeat IV fluid bolus

insertion of central venous catheter (check platelets, INR and patient's FiO2)

insertion of arterial catheter

initiation of vasopressor medications

consultation to ICU

Maintenance IV fluid/rate (after IV Fluid Bolus) mL/h

2. Antibiotics (see reverse for Antimicrobial Section)

Every effort should be made to have blood cultures collected before the initiation of antibiotics. However, DO NOT DELAY ANTIBIOTICS IF UNABLE TO COLLECT CULTURES FIRST

Antibiotics should be given within 1h of diagnosis of severe sepsis/septic shock

3. Vital Signs

Attach patient to a cardiac monitor. Arrange transfer to a step-down or ICU bed if patient on the floor or in the emergency department

BP, HR, RR, O2 saturation q15min. Temperature q4h

Ins and Outs q1h

Foley to urometer

4. Investigations STAT

ABG and lactate

Profile and differential, BUN, creatinine, blood glucose

Sodium, potassium, chloride, magnesium

CK and troponin, EKG

AST, ALT, alkaline phosphatase, bilirubin and amylase

Type and screen

Blood cultures x 2 using two sites. First site both aerobic and anaerobic vials

Urine dip, microscopy, culture and susceptibility

Sputum for culture and sensitivity

Cultures (other)

Special cultures (viral)

Chest x-ray

Other x-ray

Other investigation (for e.g., CT)

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Splenectomy Vaccination GuidelinesSplenectomy Vaccine Kit (all items go up to floor for patient)1) Post-splenectomy vaccinations Pre-Printed Order.

2) One dose of each vaccine plus package insert

• Pneumococcal polysaccharide vaccine (Pneumovax®)

• Meningococcal ACYW conjugate (Menactra®)

• Hemophilus influenzae B (Act-Hib®)

3) Splenectomy vaccines - Documentation for Family Physicians form.

4) Splenectomy - Information for Patients sheet.

5) Wallet card for Asplenic Patients sheet.

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UPDATED


Splenectomy Vaccination Guidelines

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UPDATED


Splenectomy Vaccination Guidelines

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UPDATED


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UPDATED


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UPDATED


Surgical ProphylaxisPRINCIPLES OF ANTIMICROBIAL PROPHYLAXIS

The accepted principles of antimicrobial prophylaxis for surgical procedures involve:

• Surgical procedures for which antimicrobial prophylaxis has been demonstrated to bebeneficial.

• Antimicrobial prophylaxis for “clean” surgical procedures is generally unnecessary. Forthe majority of surgical procedures in which antimicrobial prophylaxis is indicated, asingle 2 g dose of cefazolin given immediately prior to induction of anaesthesia isappropriate.

• Timing and duration of the administration of the antimicrobial is important. Ingeneral, a single dose of a parenteral antimicrobial given within 30 minutes before skinincision (i.e. immediately prior to induction of anaesthesia) provides adequate tissueconcentrations for several hours. “On call” dosing is not acceptable, as it may result inpremature administration of the antibiotic regimen and insufficient tissueconcentrations of the drug during surgery. An intra-operative dose of antibiotics shouldbe given when surgery is prolonged (i.e. more than 3 hours when the antibiotic, such ascefazolin, has a reasonably long half-life or sooner for an antibiotic with shorter half-life). If massive blood loss occurs, a second dose should be given promptly. Post-operative doses of prophylactic antibiotics are generally unnecessary. However, dosingbeyond the operative period is still recommended in such areas as cardiac surgery.

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Peri-operative Antibiotic ProphylaxisTable

AppendectomyAll patients Metronidazole 500 mg Metronidazole 500 mg • No antibiotic

Plus Plus • If gangrenous orCefazolin 2 g✿45 Gentamicin 2 mg/kg* perforated appendix

or intestine,treatment coursemust start

BreastHigh risk patients only14,15 Cefazolin 2 g✿ Vancomycin 1 g No antibiotic• Recent neoadjuvantchemotherapy or radiationtherapy• Prosthetic material or mesh• Re-operation or recent priorbreast surgery• Reconstruction surgeries• Operation duration ≥2 hours• Immunocompromised patients(diabetics, steroids, etc)

CardiacAll patients Cefazolin 2 g✿ Vancomycin 1 g 24 hours

Colorectal30

All patients Metronidazole 500 mg Metronidazole 500 mg No antibioticPlus PlusCefazolin 2 g✿ Gentamicin 2 mg/kg*

GastroduodenalHigh risk patients only Cefazolin 2 g✿ Clindamycin 600 mg No antibiotic(decreased gastric acidity and PlusGI motility) Gentamicin 2 mg/kg*• obstruction• hemorrhage• gastric ulcer or malignancy• therapy with H2 blocker or PPI• morbid obesity

HandComplex Clean Procedures: Cefazolin 2 g✿ Vancomycin 1 g 24 hours• Mutilating and crushing injuriesfrom home & industrial source• Bone, joint, tendon (exceptopen flexor tendon injuries - seebelow) and nerve involvements• Implants/prosthesis• Flap reconstruction• Injuries require amputations• High risk patients with medicalcomorbidities and/orimmunosuppressive drugs

Patient selection Pre-op IV antibiotic Post-op IVStandard Penicillin antibioticRegimen Allergy duration

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Peri-operative Antibiotic ProphylaxisTable (cont’d)

Hand (cont’d)Clean-contaminated and Cefazolin 2 g✿ Clindamycin 600 mg • 24 hours20,26

Contaminated Procedures: Plus Plus • For grossly• Mutilating and crushing Gentamicin 2 mg/kg* Gentamicin 2 mg/kg* contaminated/dirtyinjuries from farm environment Plus wounds and injuries• Grossly contaminated and Metronidazole longer than 6 hoursdirty injuries 500 mg consider a course of• Animal and human bites treatment with• Open fractures broad spectrum• Use of leeches antibiotics.

Simple Clean Procedures: No antibiotics21,22,25

• Clean simple soft tissuelacerations• Open flexor tendon injuries

18

Exception: ✥ Beyond zone IV

Head and Neck (Major)Clean procedures: Cefazolin 2 g✿ Clindamycin 600 mg Oncology patients9

• no incision of the oral or Benign patientspharyngeal mucosa • 24 hours• no implantation of prosthetic • No antibioticsmaterial• exceptions (no antibiotics): - thyroidectomy - parotidectomy - submandibular gland excision - all of above with no neck dissections and/or skull base involvement

Clean-contaminated procedures: Cefazolin 2 g✿ Clindamycin 600 mg Oncology patients9

• Require penetration of the Plus Plus • 24 hoursoral or pharyngeal mucosa Metronidazole Gentamicin 2 mg/kg* Benign patients• Complex resection with 500 mg • No antibioticsreconstruction procedures• Revision and salvage surgeries

Hepatic Pancreatic Biliary Tract (HPB)Minor Procedures Cefazolin 2 g✿ Clindamycin 600 mg No antibiotics for(Cholecystectomy etc.) Plus most patients except:• High risk patients only Gentamicin 2 mg/kg* • Acute Cholecystitis:- age >70 - 2-5 days- acute cholecystitis • Emphysematous- non functioning gall bladder acute cholecystitis:- obstructive jaundice - 5-7 days- common bile duct stones • Gangrene or

perforatedgallbladder: - change to a broad spectrum antibiotic for treatment


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Hepatic Pancreatic Biliary Tract (HPB) (cont’d)Major Procedures Metronidazole 500 mg Metronidazole 500 mg No antibiotics

Plus PlusCefazolin 2 g✿ Gentamicin 2 mg/kg*

Hernia RepairHigh risk patients only Cefazolin 2 g✿ Vancomycin 1 g No antibiotic16,17

• prosthetic material or mesh• age ≥70• immune compromised patients(diabetes, neoplasm, HIV/AIDS)• corticosteroid use• recurrent repairs• operative time ≥2 hours• routine use of drainage andprosthesis

NeurosurgeryCraniotomy Cefazolin 2 g✿ Vancomycin 1 g No antibiotic• clean, non-implant

Craniotomy13 Cefazolin 2 g✿ Vancomycin 1 g No antibiotic• clean-contaminated Plus Plus• crosses sinuses or naso/ Metronidazole 500 mg Metronidazole 500 mgoropharynx• emergency surgery• operation ≥2 hours• CSF leakage• Subsequent operation

Transsphenoidal surgery11,12

• all patients

CSF Shunting32 Cefazolin 2 g✿ Vancomycin 1 g 24 hours46,47

Obstetrics and Gynaecology2,29

Abortion1,2

• First trimester • Chlamydia - positive • Chlamydia - positive For Doxycyclineor suspected or suspected only: Doxycycline• Previous pelvic • Previous pelvic 200 mg po halfinflammatory disease, inflammatory disease, hour post-opgonorrhea or multiple gonorrhea or multiplesex partners sex partnersOral to be given 1 h Oral to be given 1 hpre-op: pre-op:Azithromycin 1 g po Azithromycin 1 g poOr OrDoxycycline 100 mg po Doxycycline 100 mg po• Bacterial vaginosis - • Bacterial vaginosis -positive or suspected positive or suspectedADD ADDMetronidazole Metronidazole500 mg po 500 mg poAll other patients: All other patients:Cefazolin 2 g✿ Clindamycin 600 mg

PlusGentamicin 2 mg/kg*


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Obstetrics and Gynaecology2,29 (cont’d)• Radical and total hysterectomy Cefazolin 2 g✿ Clindamycin 600 mg No antibiotic7

(abdominal, laparoscopic or Plusvaginal) Gentamicin 2 mg/kg*• caesarean section- administer antibiotics prior toskin incision NOT after cordclamping8• vulvectomy with or withoutlymphadenectomy• vaginectomy• urogynecological procedures- laparoscopic Burch- 2-Team sling• endometriosis (laparoscopy Metronidazole 500 mg Metronidazole 500 mg No antibioticand open) Plus Plus

Cefazolin 2 g✿ Gentamicin 2 mg/kg* No antibiotic

Oral and Maxillofacial• No oral or sinus cavity Cefazolin 2 g✿ Clindamycin 600 mg No antibioticsinvolvement• Oral cavity or sinus cavity Cefazolin 2 g✿ Clindamycin 600 mg No antibiotics19

involvement Plus• Comminuted and Metronidazole 500 mgcompounded fractures• Implants/prosthesis; bone graft• Orthognathic• Gun shot wound Cefazolin 2 g✿ Clindamycin 600 mg • 24 hours23,24

• Animal or human bite injuries Plus Plus • For grossly• Grossly contaminated and Gentamicin 2 mg/kg* Gentamicin 2 mg/kg* contaminated/dirtydirty injury Plus wounds, consider a

Metronidazole 500 mg course of treatmentwith broad spectrumantibiotics.

OrthopedicMajor procedures: Cefazolin 2 g✿ Clindamycin 600 mg 24 hours• Difficult fracture reconstruction• total hip & knee replacement• other procedures requiringprophylaxisMinor procedures: No antibiotics• arthroscopy• procedures not involvingimplantation or prostheticmaterial

Spine10

• Fusion Cefazolin 2 g✿ Vancomycin 1 g No antibiotic• Decompression• Instrumentation


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ThoracicPulmonary resection only Cefazolin 2 g✿ Vancomycin 1 g No antibiotic

Trauma (Orthopedics)27

Gun shot fracture wound Cefazolin 2 g✿ Vancomycin 1 g 48 hoursGun shot fracture wound with Cefazolin 2 g✿ Vancomycin 1 g 48 hours• large soft tissue defects or Plus Pluscavitary lesions Gentamicin 2 mg/kg* Gentamicin 2 mg/kg*AND/OR• fracture of the extremities(about the hand, foot and ankle)Gun shot fracture wound with Cefazolin 2 g✿ Vancomycin 1 g • 48 hours• large soft tissue defects or Plus Plus • For grosslycavitary lesions Gentamicin 2 mg/kg* Gentamicin 2 mg/kg* contaminated/dirtyAND/OR Plus Plus wounds and injuries• fracture of the extremities Metronidazole 500 mg Metronidazole 500 mg longer than 6 hours(about the hand, foot and ankle) consider a course ofPLUS treatment with• gross contamination of the broad spectrumwound and environment antibiotics.- occurred in rural/wooded area- grossly dirty skin and clothes- bowel communication

Trauma (Abdomen)28,31

Penetrating abdominal trauma Metronidazole 500 mg Metronidazole 500 mg 24 hours• hollow viscus injury Plus Plus

Cefazolin 2 g✿ Gentamicin 2 mg/kg*Penetrating abdominal trauma Metronidazole 500 mg Metronidazole 500 mg No antibiotic• non hollow viscus injury Plus Plus

Cefazolin 2 g✿ Gentamicin 2 mg/kg*

Urinary Diversion Procedures Involving Bowel Segments(assuming all patients have urine culture performed and all positive urine culture patients are treated before surgery)

• Ileal conduit procedures or Oral antibiotics:5

Oral antibiotics: 24 hoursprocedures involving bowel • metronidazole • metronidazolesegments 500 mg po x 3 doses 500 mg po x 3 doses• Oral AND IV antibiotics at 1, 2 & 4 hours at 1, 2 & 4 hours

Plus Plus• erythromycin • erythromycin500 mg po x 3 doses 500 mg po x 3 dosesat 1, 2 & 4 hours after at 1, 2 & 4 hours aftergastric lavage gastric lavageAND ANDIV antibiotics:

6IV antibiotics:

• Metronidazole • Metronidazole500 mg 500 mgPlus Plus• Cefazolin 2 g✿ Gentamicin 2 mg/kg*


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Urology3

(assuming all patients have urine culture performed and all positive urine culture patients are treated before surgery)

• TURP and retropubic total Oral to be given Oral to be given 24 hours4

prostatectomy 1-2 h pre-op: 1-2 h pre-op:• Transrectal and core biopsy 1. Ciprofloxacin 1. Ciprofloxacinof the prostate 500 mg po 500 mg po• Ureteroscopy & percutaneous or orstone surgery 2. Co-trimoxazole DS - 2. Co-trimoxazole DS -• implantation of prosthetic 1 tab po 1 tab podevice OR OR• impaired immune status IV regimen: IV regimen:• other open and laparoscopy 1. Cefazolin 2 g✿ 1. Gentamicin 2 mg/kg*procedures or- clean-contaminated 2. Gentamicin 2 mg/kg*procedures (open and/or entryvia urinary tract)

➢ all patients- clean procedures (no urinarytract entry)

➢ high risk patients only3

✥ advanced age✥ poor nutritional status✥ diabetes mellitus✥ smoking✥ obesity✥ coexisting infection at a

remote body site✥ colonization with

microorganisms• oral OR IV antibiotics• ureteroscopy No antibiotics• cystoscopy• open and laparoscopyprocedures- clean (no urinary tract entry)- exception: high risk patients –

see above risk factors3

Vascular Surgery43,44

• lower limb amputation Cefazolin 2 g✿ Vancomycin 1 g 24 hours• abdominal and lower limbvascular surgery• procedures involving groinincision or prosthetic material• carotid endarterectomy andbrachial arterial repair withprosthetic graft only

Patient selection Pre-op IV antibiotic Post-op IV Standard Penicillin antibiotic Regimen Allergy duration

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Intra-operative Antibiotic ProphylaxisTable:42

Antibiotic Duration of operation Blood loss >1.5L Pre-op administration>3 hours time

Cefazolin✿ Repeat 1 g q3H33,34,36 Repeat 1 g x 1 dose 0-60 minutes prior to skinException: CrCL ≤30 mL/min only39,40 incision• repeat 1 g q6h

Ciprofloxacin po Operation >6 hours, No data – 60-120 minutes prior toadminister Cefazolin 1g q3h no recommendation skin incisionCrCL ≤30 mL/min, operation >120 minutes prior to skin>12 hours, administer incision, repeatCefazolin 1 g q6h ciprofloxacin 500 mg po x

1 dose at inductionClindamycin Repeat q6h No data – 0-60 minutes prior to skin

no recommendation incisionCo-trimoxazole Operation >6 hours, No data – 60-120 minutes prior toDs po administer Cefazolin 1 g q3h no recommendation skin incision

CrCL ≤30 mL/min, operation No data – >120 minutes prior to skin>24 hours, administer no recommendation incision, repeatCefazolin 1 g q6h co-trimoxazole DS 1 tab

po x 1 dose at inductionGentamicin* Repeat 1 dose only intra-op Repeat 1 dose only38,40 60 minutes prior to skin

at 3h after initial dose 37 incision allowException: CrCL ≤60 mL/min Exception: CrCL ≤60 mL/ 30 minutes for infusionor min or of drugs allowMales: SCr ≥135 μmol Males: SCr ≥135 μmol another 30 minutesFemales: SCr ≥125 μmol Females: SCr ≥125 μmol for distribution of drugs• no intra-op dose • no intra-op dose

Metronidazole Repeat q12h No data – 0-60 minutes prior to skinno recommendation incision

Vancomycin Repeat q12h41 No intra-op dose 60-120 minutes prior toException: CrCL ≤30 mL/min needed35 skin incision allow• repeat q24h 60 minutes infusion

time for dose of 1 g

* All gentamicin doses will be rounded to the nearest 20 mg.

✿ Cefazolin 2 g is for pre-operative dosing only. Intra-operative and post-operative dosing for cefazolinwill remain 1 g.

Post-operatively resume regular treatment frequency. Adjust as needed for renal impairmentpatients.

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References

1. Abramovicz M et al. Treatment Guidelines from The Medical Letter – AntimicrobialProphylaxis for Surgery. The Medical Letter; 5(52): 83-87, 2006

2. Capital Health Edmonton, Recommended Drug Regimens for Surgical Prophylaxis.Capital Health Edmonton 2006

3. Grabe M. Controversies in Antibiotic Prophylaxis in Urology. International Journal ofAntimicrobial Agents; 23(S1): S17-S23, 2004

4. Takeyama K et al. Prophylactic Antimicrobial Agents in Urologic Laparoscopic surgery: 1day versus 3 day Treatments. Journal of Infection Chemotherapy; 10: 168-171, 2004

5. Ferguson KH et al. Mechanical and Antibiotic Bowel Preparation for Urinary DiversionSurgery. The Journal of Urology; 167: 2352-2356, 2002

6. Takeyama K et al. Incidence of and Risk Factors for Surgical Site Infection in Patients withRadical Cystectomy with Urinary Diversion. Journal of Infection Chemotherapy; 11: 177-181, 2005

7. Mayer HO et al. Perioperative Antibiotic Prophylaxis in Patients Undergoing RadicalSurgery for Gynecologic Cancer: Single Dose versus Multiple Dose Administration.European Journal of Gynaecology Oncology; 14(3): 177-181, 1993.

8. Sullivan SA et al. Administration of Cefazolin Prior to Skin Incision is Superior to Cefazolinat Cord Clamping in Preventing Postcesarean Infectious Morbidity: a Randomized,Controlled Trial. American Journal of Obstetrics & Gynecology; 455: e1-e5, 2007

9. Simo R et al. The Use of Antibiotic Prophylaxis in Head and Neck Oncological Surgery.Current Opinion in Otolaryngology & Head and Neck Surgery; 14: 55-61, 2006

10. Barker FG et al. Efficacy of Prophylactic Antibiotic Therapy in Spinal Surgery: A Meta-analysis. Neurosurgery; 51(2): 391-400, 2002

11. Orlando R et al. Retrospective Analysis of a new Antibiotic Chemoprophylaxis Regimen in170 Patients Undergoing Endoscopic Endonasal Transspehnoidal Surgery. SurgicalNeurology; 68: 145-148, 2007

12. Van Aken MO et al. Risk Factors for Meningitis After Transsphenoidal Surgery. ClinicalInfectious Diseases; 25: 852-856, 1997

13. Korinek A et al. Risk Factors for Neurosurgical Site Infections after Craniotomy: AProspective Multicenter Study of 2944 Patients. Neurosurgery; 41(5): 1073-81, 1997

14. Tejirian T et al. Antibiotic Prophylaxis for Preventing Wound Infection after Breast Surgery:A Systematic Review and Metaanalysis. The American College of Surgeons; 203(5): 729-734, 2006

15. Cunningham M et al. Prophylactic Antibiotics to Prevent Surgical Site Infection AfterBreast Cancer Surgery. The Cochrane Database Of Systematic Reviews, The CochraneLibrary; 4: 2007

16. Sanabria A et al. Prophylactic Antibiotics for Mesh Inguinal Hernioplasty: A Meta-analysis.Annals of Surgery; 245(3): 392-396, 2007

17. Sanchez-Manuel et al. Antibiotic Prophylaxis for Hernia Repairs: The Cochrane Databaseof Systematic Reviews. The Cochrane Library; 1, 2008

18. Stone JF et al. The Role of Antibiotics and Timing of Repair in Flexor Tendon Injuries of theHand. Annals of Plastic Surgery; 40(1): 7-13, 1998

19. Andreasen JO et al. A Systematic Review of Prophylactic Antibiotics in the SurgicalTreatment of Maxillofacial Fractures. Journal of Oral Maxillofacial Surgery; 64: 1664-1667,2006

20. Hoffman RD et al. The Role of Antibiotics in the Management of Elective and Post-traumatic Hand Surgery. Hand Clinics; 14(4): 657-666, 1998

21. Whittaker JP et al. The Role of Antibiotic Prophylaxis in Clean Incised Hand Injuries: AProspective Randomized Placebo Controlled Double Blind Trial. Journal of Hand SurgeryBritish & European; 30B(2): 162-167, 2005

22. Roberts AHN et al. A Prospective Trial of Prophylactic Antibiotics in Hand Lacerations.British Journal of Surgery; 64: 394-396, 1977

23. Kassan AH et al. A Retrospective Analysis of Gunshot Injuries to the Maxillofacial Region.South African Dental Journal; 55: 359-63, 2000

24. Liston PN. Bite Injuries: Pathophysiology, Forensic Analysis and Management. NewZealand Dental Journal; 97: 58-63, 2001

94-102 12/12/11, 2:02 PM101


25. Al-Nammari SS et al. Conservative Management or Suturing for Small, UncomplicatedHand Wounds. Emergency Medicine Journal; 24: 217-218, 2007

26. Platt AJ et al. Post-operative Infection Following Hand Surgery; Guidelines for AntibioticUse. Journal of Hand Surgery (British & European Volume); 20B(5): 685-690, 1995

27. Simpson BM et al. Antibiotic Therapy in Gunshot Wound Injuries. Clinical Orthopaedicsand Related Research; 408: 82-85, 2003

28. Bozorgzdeh A et al. The Duration of Antibiotic Administration in Penetrating AbdominalTrauma. The American Journal of Surgery; 177: 125-131, 1999

29. ACOG Practice Bulletin – Clinical Management Guidelines for Obstetrician-Gynecologists,bulletin number 23. Obstetrics & Gynecology; 108(1): .225-234, 2006

30. Espin-Basany E et al. Prospective, Randomized Study on Antibiotic Prophylaxis inColorectal Surgery. Is it Really Necessary to Use Oral Antibiotics? International Journal ofColorectal Disease; 20: 542-546, 2005

31. Delgado G et al. Characteristics of Prophylactic Antibiotic Strategies After PenetratingAbdominal Trauma at a Level I Urban Trauma Center: A Comparison with the EASTGuidelines. The Journal of Trauma Injury, Infection, and Critical Care; 53(4): 673-678,2002

32. Langley JM., LeBlanc JC et al. Efficacy of Antimicrobial Prophylaxis in Placement ofCerebrospinal Fluid Shunts: Meta-Analysis. Clinical Infectious Diseases; 17: 98-103, 1993

33. Morita S, Nishisho N et al. The Significance of the Intraoperative Repeated Dosing ofAntimicrobials for Preventing Surgical Wound Infection in Colorectal Surgery. SurgeryToday; 35: 732-738, 2005

34. Hiroki O, Yoshio T et al. An Additional Dose of Cefazolin for Intraoperative Prophylaxis.Surgery Today; 29: 1233-1236, 1999

35. Cameron DR, Muller MJ, Faoagali J. Burn Wound Excision and Massive Blood Transfusiondid not Affect Perioperative Vancomycin Levels. Burns; 24: 475-477, 1998

36. Zanetti G. Intraoperative Redosing of Cefazolin and Risk for Surgical Site Infection inCardiac Surgery. Emerging Infectious Diseases; 7(5), 2001

37. Zelenitsky SA, Silverman RE et al. A prospective, randomized, double-blind Study of SingleHigh Dose versus Multiple standard Dose Gentamicin Both in Combination withMetronidazole for Colorectal Surgical Prophylaxis. Journal of Hospital Infection; 46(2),2000

38. Markantonis SL, Kostopanagiotou G et al. Effects of Blood Loss and Fluid VolumeReplacement on Serum and Tissue Gentamicin Concentrations During Colorectal Surgery.Clinical Therapeutics; 26(2): 271-281, 2004

39. Zelenitsky SA, Ariano RE et al. Antibiotic Pharmacodynamics in surgical Prophylaxis: anAssociation between Intraoperative Antibiotic Concentrations and Efficacy. AntimicrobialAgents and Chemotherapy; 46(9): 3026-3030, 2002

40. Swoboda SM, Merz C et al. Does Intraoperative Blood Loss Affect Antibiotic Serum andTissue Concentrations? Archives Surgery; 131(11): 1165-1172, 1996

41. Vuorisalo S, Podela R, Syrjala H. Is Single-dose Antibiotic Prophylaxis Sufficient forCoronary Artery Bypass Surgery? An Analysis of Peri- and Post-operative SerumCefuroxime and Vancomycin Levels. Journal of Hospital Infection; 37: 237-247, 1997

42. Micromedex Healthcare Series on Cefazolin, Clindamycin, Gentamicin, Ciprofloxacin, Co-trimoxazole, Metronidazole and Vancomycin

43. Pounds LL et al. A Changing Pattern of Infection After Major Vascular Reconstructions.Vascular and Endovascular Surgery; 39(6): T1-T7, 2005

44. Chang JK et al. Risk Factors Associated with Infection of Lower ExtremityRevascularization: Analysis of 365 Procedures Performed at a Teaching Hospital. Annals ofVascular Surgery - International Journal of Vascular Surgery; 17: 91-96, 2003

45. Edmiston CE et al. Perioperative Antibiotic Prophylaxis in the Gastric Bypass Patient: DoWe Achieve Therapeutic Levels? Surgery; 136(4): 738-747, 2004

46. Costa RB et al. Antibiotic Prophylaxis for Surgical Introduction of Intracranial VentricularShunts; The Cochrane Database of Systematic Reviews; 4, 2007

47. Langley JM, LeBlanc JC et al. Efficacy of Antimicrobial Prophylaxis in Placement ofCerebrospinal Fluid Shunts: Meta-Analysis. Clinical Infectious Diseases; 17: 98-103, 1993

Adapted from Sunnybrook Health Sciences Centre

94-102 12/12/11, 2:02 PM102


103-114 12/12/11, 2:05 PM103


Urinary Tract Infections (UTIs)UTI Classifications

Lower urinary tract• Urethritis• Cystitis• Prostatitis

Upper urinary tract• Pyelonephritis

Infection Type

• Acute: recent onset of UTI symptoms

• Chronic: ongoing, unresolved infection, may be due to structural defects orobstructions and/or resistant or multiple organisms

• Recurrent: symptomatic infection that recurs within 2 weeks of a prior infection withthe same organism or reinfection with a new organism

• Complicated: Acute or chronic UTI with complicating factors such as relapsinginfection, diabetes, pregnancy, altered immune status, structural abnormalities, orcatheterization

• Uncomplicated: UTI without presence of complicating factors

Diagnosis

Must be confirmed by laboratory tests because of the unreliability of symptoms.

Urinalysis

• The presence of leukocytes is non specific and may be indicative of inflammation only

• WBC casts may indicate pyelonephritis

• The following degrees of bacteriuria are often considered to be clinically significant:Greater than 102 CFU coliforms/mL in symptomatic womenGreater than 103 CFU coliforms/mL in symptomatic menGreater than 105 CFU coliforms/mL in asymptomatic patients on two consecutivespecimensGreater than 102 CFU coliforms/mL in a catheterized patient with symptomsAny growth of bacteria on a suprapubic catheterization in a symptomatic patient

Nitrite test is used as a marker for bacteriuria, but not all uropathogens reduce nitrates tonitrites. (i.e. Enterococci, S. Saprophyticus and Acetinobacter do not and thus give false-negative results.)

Culture and sensitivity allows identification of the infecting organism(s) and thedetermination of antibiotic sensitivities

Blood cultures should be considered with pyelonephritis and severe complicated UTIs

Asymptomatic Bacteriuria

• Presence of bacteria in voided urine with no symptoms of urinary tract infection

• Treatment is not recommended in the non-catheterized elderly, unless the patient issymptomatic

• Pregnant women, patients about to undergo urological surgery, immunocompromisedpatients should be treated for asymptomatic UTIs.

103-114 12/12/11, 2:05 PM104

UPDATED

Feb 20

19


Management of UTIs

Cat

egor

yPo

tent

ial

path

ogen

sFi

rst l

ine

ther

apy

(cos

t)Se

cond

line

ther

apy

(cos

t)

Acu

te u

ncom

plic

ated

E.co

li, S.

sapr

ophy

ticus

,Su

lfam

etho

xazo

le/T

rimet

hopr

im D

S tab

q12

h x

Cip

roflo

xaci

n* 2

50 m

g q1

2h x

3 d

ays1

cyst

itis◊

Prot

eus,

Kleb

siella

3 da

ys o

r Nitr

ofur

anto

in 5

0-10

0 m

g q6

h x

7 da

ysC

epha

lexi

n 50

0 m

g qi

d x

7 da

ysA

cute

cys

titi

s in

men

requ

ires

7 d

ays o

fFo

sfom

ycin

3 g

x 1

dos

eth

erap

y no

mat

ter w

hat a

gent

is u

sed

Acu

te c

ysti

tis i

n m

en re

quir

es 7

day

s of

ther

apy

no m

atte

r wha

t age

nt is

use

d

Acu

te c

ysti

tis

E.co

li, P

rote

us, K

lebs

iella

,Am

oxic

illin

250

- 500

mg

q8h

x 7

days

Sulfa

met

hoxa

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/Trim

etho

prim

DS t

ab q

12h

(pre

gnan

t wom

en)

Ente

roco

cci

(avo

id 1

st/l

ate

3rd

trim

este

rs) o

rC

epha

lexi

n 25

0 m

g q6

h or

Nitr

ofur

anto

in50

-100

mg

q6h

for 3

-7 d

ays

Avoi

d te

trac

yclin

es a

nd q

uino

lone

s

Acu

te p

yelo

neph

riti

sE.

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teus

, Kle

bsie

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Seve

re:

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r(T

he re

sults

of p

re-

Ente

roco

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Ente

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cter

,Am

pici

llin

1-2

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h IV

+C

ipro

floxa

cin*

400

mg

IV q

12h2,

4

trea

tmen

t C/S

shou

ld b

eS.

sapr

ophy

ticus

Gen

tam

icin

6 m

g/kg

IV d

aily

(adj

uste

dSt

ep d

own

to o

ral t

hera

py fo

r a to

tal o

fus

ed to

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ct th

erap

y)to

rena

l fun

ctio

n) S

tep

dow

n to

ora

l14

day

s3 : C

ipro

floxa

cin

500

mg

q12h

1,4

Con

sider

the u

se o

fth

erap

y fo

r a to

tal o

f 14

days

3 :or

Am

oxic

illin

/Cla

vula

nate

875

mg

q12h

1

bloo

d cu

lture

sSu

lfam

etho

xazo

le/T

rimet

hopr

im D

S tab

q12

hD

o no

t use

nit

rofu

rant

oin

Mild

to m

oder

ate:

Cip

roflo

xaci

n 50

0 m

g po

q12

h x

10-1

4 da

ys

Com

plic

ated

UTI

sE.

coli,

Pro

teus

, Kle

bsie

lla,

Ora

l the

rapy

: Sul

fam

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xazo

le/T

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ral t

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ipro

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cin*

250

-500

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(The

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f pre

-En

tero

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tero

bact

er,

DS t

ab q

12h

or N

itrof

uran

toin

q12h

1 or A

mox

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in/C

lavu

lana

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eatm

ent C

/S sh

ould

be

S.sa

prop

hytic

us,

50-1

00 m

g fo

r 10-

14 d

ays

875

mg

q12h

1 fo

r 10-

14 d

ays.

used

to d

irect

ther

apy)

Pseu

dom

onas

aeu

rugi

nosa

IV th

erap

y:IV

ther

apy:

Rem

ove c

athe

ter i

fAm

pici

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1-2

g q6

h IV

+C

eftr

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ne 1

g q

24h1

orca

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late

d U

TIG

enta

mic

in 6

mg/

kg IV

dai

lyC

ipro

floxa

cin*

200

-400

mg

IV q

12h2

Con

sider

the u

se o

f(a

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ted

to re

nal f

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Step

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ora

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rapy

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ep d

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ral t

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f 10-

14 d

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for a

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ue to

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, E. c

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omyc

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103-114 12/12/11, 2:05 PM105

UPDATED

Feb 20

19


Management of UTIs (cont’d)Se

veri

tyPo

tent

ial

path

ogen

sFi

rst l

ine

ther

apy

(cos

t)Se

cond

line

ther

apy

(cos

t)

Recu

rren

t cys

titi

sE.

coli,

Pro

teus

, Kle

bsie

lla,

Early

recu

rren

ce (<

30

days

):C

onsid

er p

roph

ylax

is fo

r 3 o

r mor

e rec

urre

nces

Ente

roco

cci,

Ente

roba

cter

,Re

trea

t for

acu

te cy

stiti

s but

per y

ear:

Sulfa

met

hoxa

zole

/Trim

etho

prim

one

-hal

fS.

sapr

ophy

ticus

for 1

0-14

day

sto

one

tab

or n

itrof

uran

toin

50

mg

qhs d

aily

Can

didu

ria

inC

andi

daO

ral t

hera

py: F

luco

nazo

le 2

00 m

gIV

ther

apy:

Flu

cona

zole

200

mg

daily

for

sym

ptom

atic

pat

ient

sda

ily fo

r 3 to

7 d

ays

3 to

7 d

ays2

with

risk

fact

ors s

uch

as IC

U se

ttin

g,im

mun

osup

pres

sion

1. T

reat

men

t of U

TIs d

ue to

resis

tant

org

anism

s or f

or p

atie

nts w

ith re

nal i

mpa

irmen

t or a

llerg

ies w

hich

pre

clud

e the

use

of o

ther

age

nts

2. R

estr

icte

d to

ID o

r IC

U p

hysic

ians

3. M

ay b

e pos

sible

to in

itiat

e the

rapy

with

ora

l age

nts i

n th

e abs

ence

of n

ause

a an

d vo

miti

ng4.

The

add

ition

of a

mpi

cilli

n/am

oxic

illin

may

be n

eces

sary

in th

e pre

senc

e of e

nter

ococ

ci

103-114 12/12/11, 2:05 PM106

UPDATED

Feb 20

19


Vancomycin Usage GuidelinesRecommendations for Appropriate Use of Vancomycin

Prudent antibiotic use is critical to stem the rise of vancomycin-resistant enterococci (VRE),and even hospitals where the pathogen has not been detected should develop plans tocurtail inappropriate use of vancomycin. Situations in which the use of vancomycin isappropriate and inappropriate are summarized below.

Using vancomycin is appropriate:• for treatment of serious infections due to beta-lactam resistant, gram-positive

microorganisms. (Clinicians should be aware that vancomycin may be less rapidlybactericidal than beta-lactam agents for beta-lactam susceptible staphylococci.);

• for treatment of infections due to gram-positive microorganisms in patients withserious allergy to beta-lactam antimicrobials;

• when antibiotic-associated colitis (AAC) fails to respond to metronidazole therapy, orif AAC is severe and potentially life-threatening;

• for prophylaxis, as recommended by the American Heart Association, for endocarditisfollowing certain procedures in high-risk patients;2

• as prophylaxis for surgical procedures involving implantation of prosthetic materialsor devices at institutions with a high rate of infections due to methicillin-resistantStaphylococcus aureus (MRSA) or Staphylococcus epidermidis (MRSE). A single doseadministered immediately before surgery is sufficient unless the procedure lasts morethan six hours, in which case the dose should be repeated. Prophylaxis should bediscontinued after a maximum of two doses.

Using vancomycin is inappropriate for:• routine surgical prophylaxis;• empiric antimicrobial therapy for a febrile neutropenic patient, unless there is strong

evidence at the onset that the patient has an infection due to gram-positivemicroorganisms and the prevalence of infections due to beta-lactam-resistant, gram-positive microorganisms (e.g. MRSA or MRSE) in the hospital is substantial;

• treatment in response to a single blood culture positive for coagulase-negativeStaphylococcus, if other blood cultures drawn in the same time frame are negative.(Contamination of blood cultures with skin flora may cause vancomycin to beadministered inappropriately to patients. Phlebotomists and other personnel whoobtain blood cultures should be trained properly to minimize microbial contaminationof specimens.);

• continued empiric use for presumed infections in patients whose cultures are negativefor beta-lactam-resistant, gram-positive microorganisms;

• systemic or local prophylaxis for infection or colonization of indwelling central orperipheral intravascular catheters and vascular grafts;

• selective decontamination of the digestive tract;• eradication of MRSA colonization;• primary treatment of AAC, except if moderate to severe or contains binary toxin;• routine prophylaxis for patients on continuous ambulatory peritoneal dialysis.

103-114 12/12/11, 2:05 PM107

UPDATED

Feb 20

19


Vancomycin Dosing Guidelines (cont’d)1. INITIAL DOSAGE REGIMEN

The usual initial dose is 15 mg/kg of total body weight (round to the nearest 250 mg),unless seriously ill (20-25 mg/kg).

The interval should be based on the patient’s estimated creatinine clearance.

There is a degree of patient variability in volume of distribution and drug clearance whichmakes it difficult to determine the ideal dosing regimen for an individual. There are manynomograms available for dosing based on creatinine clearance and weight but individualpatient response remains somewhat unpredictable.

CLcr (mL/min) >75 40-75 25-39 15-24 <15dosing interval 12 hours 24 hours 48 hours 72 hours 5-7 days

Hemodialysis 20 mg/kg IV then 500 mg post dialysis (as a supplemental dose), (aim for levelspre-dialysis 7.5 - 20 mg/L) or 1 g post dialysis (if severe infection or MRSA) aim for level 15-25mg/L.

2. RATIONALE FOR USE OF PRE (Trough) SAMPLES FOR THERAPEUTICDRUG MONITORING

Efficacy – Vancomycin exhibits time-dependant killing at concentrations >0.5 mg/L witha minimum inhibitory concentration (MIC) for susceptible bacteria usually <2 mg/L.Vancomycin exhibits minimal post-antibiotic effect and does not display concentrationdependant killing. There seems to be general consensus in the current literature thatmaintaining a trough concentration above 10 mg/L is desirable for optimal therapeuticresponse. There is no evidence to suggest that the peak serum concentration has anybearing on efficacy. In some cases pre/post pairs may be preferable to provide dosageadjustment recommendations based on calculated pharmacokinetic data. The post resultsin this case should be drawn post-distribution (i.e. 2 hours after the end of infusion).

Ototoxicity – This problem is less frequent than originally feared, especially whenvancomycin is used alone.

Nephrotoxicity – There appears to be a very low incidence of nephrotoxicity whenvancomycin is used alone. However, when used in combinations with aminoglycosidesthe incidence increases beyond that of either drug used alone. There is recent evidence tosuggest that the number of nephrotoxic agents used may be one of the most importantfactors in predisposing a patient to nephrotoxicity.

3. THERAPEUTIC RANGE

Optimal predose vancomycin level depends on the organism and type of infectionbeing treated:• 5-10 mg/L - mild to moderate infections; infections involving coagulase negative

staphylococci or enterococci• 10-15 mg/L - Staphylococcus aureus NOT MRSA• 15-20 mg/L - severe infections including osteomyelitis, meningitis and en-

docarditis or infection with MRSA• For organisms with an MIC ≥2 consult ID as an alternate agent should be

considered.

103-114 12/12/11, 2:05 PM108

UPDATED

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19


Vancomycin Dosing Guidelines (cont’d)4. SERUM DRUG CONCENTRATION MONITORING

All patients started on vancomycin should have a steady state pre (trough) levelobtained. To assure steady state has been achieved, the level should be drawn justbefore the 4th or 5th dose, not sooner. Adjustments to the dosage regimen may bemade as follows:Continued monitoring could be achieved by following the Scr (M,W,F) anddrawing a pre (trough level) if Scr increases 25% above baseline or every five days iftherapy is continued.

Additional monitoring is required for the following patients:1. Patients with severe renal impairment (CLcr <25 mL/min) - trough level every

second dose.2. Burn patients, intravenous drug abusers, or dehydrated patients - pre and post

levels should be drawn due to high variability of clearance and/or volume ofdistribution within an individual patient.

3. Dialysis patients - trough levels drawn prior to dialysis.

103-114 12/12/11, 2:05 PM109

UPDATED

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19


Sequential Antibiotic Therapy andPharmacist Initiated Route ofAdministration Therapeutic Interchange

SEQUENTIAL ANTIBIOTIC THERAPY (SAT) refers to the practice of limiting intravenous(IV) antimicrobials to the early stages of infection and then converting to oral agents forthe duration of treatment. The concept of sequential antibiotic therapy or “steppingdown”or “switching” is a natural sequence in patient care, with many potential benefits:• Provides similar blood/tissue levels as IV (with some agents identical levels)• Maintains the same spectrum of activity• Is well tolerated by the patient• Improves patient comfort• Involves less nursing time• Decreases the risk of line-related phlebitis and infections• May facilitate an earlier discharge• Is less expensive

The following Therapeutic Interchange policies enable the pharmacist to change the routeof administration of a drug when, following an assessment of the patient, this is deemedclinically appropriate. Drug therapy initiated intravenously can often be switched to asuitable oral regimen, particularly those drugs that are well-known to exhibit a high degreeof oral bioavailability. Selecting the oral administration route over the more expensiveintravenous route can be appropriate in many situations.

For drugs affected by this policy, the pharmacist may change the route of administrationfor an ordered medication when he or she has personally assessed the patient, and thepatient meets the following criteria:

• The patient is tolerating oral medications, is receiving as a minimum a clear fluid diet or isenterally fed, and

• The patient does not have/is not experiencing any of the following;➝ severe nausea and/or vomiting➝ malabsorption syndrome➝ severe sepsis➝ GI obstruction.

Preparation/regimen ordered Dispensed as

Ciprofloxacin 200 mg IV Ciprofloxacin 250 mg po (same frequency)

Ciprofloxacin 400 mg IV Ciprofloxacin 750 mg po (same frequency) or in thecase of UTI, cirpofloxacin 500 mg po (same frequency)

Fluconazole _____ mg IV Fluconazole _____mg po (same frequency)

Levofloxacin 500 mg IV daily Levofloxacin 500 mg po daily

Levofloxacin 250 mg IV daily Levofloxacin 250 mg po daily

Metronidazole 500 mg IV q12h or bid Metronidazole 500 mg po q8h

103-114 12/12/11, 2:05 PM110

UPDATED

2017


Potential Savings Intravenous-to-Oral(IV to PO) Stepdown Program1

IV Drug/Dosage/Cost per Day2 PO Drug/Dosage/Cost per Day Daily CostSavings3

Acyclovir 5 mg/kg q8h $18.454

Acyclovir 400 mg q8h $3.90 $14.55

OR Valacyclovir 500 mg q12h $3.18 $6.36

Ampicillin 1 g q6h $7.04 Amoxicillin 500 mg q8h $0.03 $7.69

OR Amoxicillin/Clavulanate

875/125 mg q12h $4.56 $2.48

Azithromycin 500 mg q24h $20.36 Azithromycin 250 mg q24h $4.74 $15.62

Cefazolin 1 g q8h $7.68 Cephalexin 500 mg q6h $0.68 $7.00

Cefuroxime Sodium 750 mg q8h $13.05 Cefuroxime Axetil 500 mg q12h $5.16 $7.89

Ceftriaxone 1 g q24h $35.15 Cefuroxime Axetil 500 mg q12h $5.16 $16.86-$29.99

OR OR

Cefotaxime 1 g q8h $22.02 Ciprofloxacin 500 mg q12h +

Cephalexin 500 mg q6h $2.00 $20.02-$33.15

Ciprofloxacin 200-400 mg q12h $33.00-66.00 Ciprofloxacin 250-750 mg q12h $0.60 $32.40-$65.73

Clindamycin 600 mg q8h $10.59 Clindamycin 300-450 mg q6h $4.28-6.42 $4.17-$6.31

Cloxacillin 1-2 g q6h $8.80-$11.60 Cloxacillin 500 mg q6h $0.32 $8.48-$11.28

Doxycycline 100 mg once daily $15.15 Doxycycline 100 mg once daily$0.30 $14.85

Levofloxacin 500 mg q24h $35.15 Levofloxacin 500 mg q24h $4.00 $31.15

Linezolid 600 mg q12h $191.02 Linezolid 600 mg q12h $143.14 $47.88

Imipenem 500 mg q6h $24.40 Ciprofloxacin 500-750 mg q12h +

Metronidazole 500 mg q8h $2.64 $21.00

OR

Ciprofloxacin 500-750 mg q12h +

Clindamycin 300 mg q6h $6.77 $18.00

Piperacillin/Tazobactam 4.5 g q8h $67.05 Ciprofloxacin 500-750 mg q12h +

Metronidazole 500 mg q8h $2.64 $64.41-$65.56

OR OR

Piperacillin/Tazobactam 3.375 g q6h $68.20 Ciprofloxacin 500-750 mg q12h +

Clindamycin 300 mg q6h $6.77 $60.28-$61.43

Trimethoprim/Sulfamethoxazole Trimethoprim/Sulfamethoxazole

5/25 mg/kg q6h $64.004

1 DS q12h $0.16 $32.00-$64.00

Voriconazole 400 mg q12h $560.00 Voriconazole 200 mg q12h $100.00 $460.00

1.These are examples only, choice of stepdown therapy must be individualized.

2.Assumes fixed cost of $1.15 per IV dose for IV bag (exceptions: ciprofloxacin, fluconazole, linezolid and

metronidazole available ready to administer).

3.Does not include saving in nursing/pharmacy time, IV tubing, etc.

4. IV cost based on a 80 kg patient.

103-114 12/12/11, 2:05 PM111

OUTDATED


Bioavailability of Oral Antibiotics

Food = take with foodES = empty stomach< - > = without regards to meals1. The presence of food in the GI tract results in lower and delayed peak serum

concentrations but the total amount of drug absorbed is unaffected.2. Bioavailability increases with food or milk.3. Calcium, aluminum, magnesium and iron salts decrease oral bioavailability; milk/

yogurt decrease bioavailability by 30-50%.4. Calcium, aluminum, magnesium and iron salts should be spaced.

Name Bioavailablility t1/2 (h) Administration

Penicillins

Amoxicllin 60-89 1 < - >

Amoxicillin/Clavulanate 60-89 1 < - >

Cloxacillin 35-70 1 ES

Penicillin VK 35-70 1 < - >1

Cephalosporins

Cephalexin 80-100 0.5-1.3 < - >

Cefuroxime axetil 30-50 1.2-1.3 Food2

Fluoroquinolones

Ciprofloxacin 69-85 3-5 < - >3,4

Levofloxacin 99 6-8 < - >1,3,4

Macrolides

Clarithromycin 50 3.4 < - >1

Erythromycin 18-45 1.4 ES

Tetracyclines

Doxycycline 90-100 18 < - >1

Tetracycline 75-80 8.5 ES1,4

Miscellaneous

Clindamycin 90 2.4 < - >

Linezolid 100 4-5 < - >

Metronidazole 90-100 6-14 < - >1

Trimethoprim/Sulfamethoxazole 85-90 11/9 < - >

Antivirals

Amantadine 86-90 12 < - >

Acyclovir 15-30 2.2-5.0 < - >

Valacyclovir 55 3 < - >

Valganciclovir 60 4 Food2

Antifungals

Fluconazole 90 24 < - >

Itraconazole 55 17-24 Food2

Ketoconazole Variable(↑ with ↓ pH) 6.5-9.6 Food2

Voriconazole 96 6 ES

103-114 12/12/11, 2:05 PM112


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Notes____________________________________________________________________________________

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103-114 12/12/11, 2:05 PM114

Prepared by: Department of Pharmacy, Division of Infectious Diseases, Capital Health, Halifax©

Designed and Printed by: CH Audio Visual and Printing Departments

QV85-0173 Rev.01/2012

Capital Health promotes a smoke-free and scent-free environment.Please do not use perfumed products. Thank you!

Capital Health, Nova Scotiawww.cdha.nshealth.ca

0173-BackCover2011 1/9/12, 3:19 PM1

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