MSH-UHN Antimicrobial Stewardship Clinical Summariesantimicrobialstewardship.com/sites/default/files/mshuhn... · ANATOMICAL. Antimicrobial Stewardship Clinical Summaries. Septic

ANTIMICROBIAL STEWARDSHIPCLINICAL SUMMARIES

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ANATOMICAL

Antimicrobial Stewardship Clinical Summaries

Septic Arthritis

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Osteomyelitis

Bone

Community Acquired Meningitis

Nosocomial Meningitis

Central Nervous System

Diabetic Foot InfectionsFoot

GastrointestinalClostridium Difficile (CDI)

Acute exacerbation of COPD

Hospital-acquired Pneumonia

Lung

Skin & Skin Structure InfectionsSkin

VascularCentral Line Infections

DRUG USE GUIDELINES

β-Lactam Allergy

Empiric Use of Antifungals

Prophylaxis for UGI Bleeding

Role of TMP-SMX

ORGANISMCandidemia (Yeast) Influenza

PsA Single vs Double Coverage

S. aureus Bacteremia



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NATIVE JOINT SEPTIC ARTHRITIS

1 EMPIRIC CHOICE 2

cefazolin 2 g iv q8h 3 If high suspicion for Neisseria gonorrhoeae: ceftriaxone 2 g iv q24h 4 If high suspicion for MRSA: vancomycin 5

6 DURATION 7

Non-gonococcal: 2-4 weeks 8 Gonococcal: 7-10 days 9

10 11 ALTERNATIVES FOR ALLERGIES 12

See 1-page document on beta-lactam allergies: 13 o cefazolin does not have a similar side chain to any other beta-lactam so can safely be used for patients 14

with previous beta-lactam hypersensitivity reactions, except those with a previous reaction to cefazolin 15 o ceftriaxone can safely be used in patients with previous beta-lactam hypersensitivity reactions EXCEPT 16

those with a previous reaction to cefepime, cefotaxime or ceftriaxone 17 Vancomycin can be used as an alternative for allergy in non-gonococcal septic arthritis 18 For patients with gonococcal septic arthritis and beta-lactam allergy, consult ID for treatment recommendations 19

20 21 TOP ORGANISMS 22

Staphylococcus aureus 23 Streptococci 24 Neisseria gonorrhoeae 25

26 27 CURRENT RESISTANCE ISSUES 28

Fluoroquinolone resistant Neisseria gonorrhoeae are frequently encountered, therefore they are not a good 29 empiric choice for gonococcal disease 30

31 32 IMMUNOCOMPROMISED HOST CONSIDERATION 33

Same as for immunocompetent hosts 34 35 36 ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS 37

Joint aspiration is almost always needed for diagnosis 38 Orthopedic surgery consultation is usually required for 39

a. diagnosis 40 b. ensuring adequate joint drainage, and 41 c. adjunctive therapy (e.g. role of splinting, physiotherapy, etc…) 42

43 44 45 46

CONSULT

Ortho

Prosthetic Joint

Infections CONSULT ID & Ortho

Disclaimer: This document is intended for internal use at Mount Sinai Hospital and University Health Network. Recommendations herein are based on existing literature and clinical practice and are subject to change at any time. Please refer to the Terms and Conditions for more details.

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Acute Osteomyelitis

Antibiotics should be withheld until sterile tissue cultures are obtained, unless the patient is septic or there is a concomitant soft tissue infection. Identification of the causative organism is very important in order to treat appropriately. EVALUATION

Obtain sterile tissue cultures by percutaneous aspirate or surgical deep culture (ideally before starting antibiotics)

Wound swabs tend to reflect colonization, and often do not indicate the infecting organism at the site of osteomyelitis

If septic, draw blood cultures

EMPIRIC CHOICE For diabetic foot infections, refer to the 1-page document on that topic Acutely Unwell or Septic:

o ceftriaxone 2 g iv q24h +/- metronidazole 500 mg p.o./iv q12h (add metronidazole for sacral osteomyelitis) +/- vancomycin (if known to be colonized/previous infection with MRSA)

o if known to be ESBL colonized/previous infection: Meropenem 1 g iv q8h +/- vancomycin if known to be colonized/previous infection with MRSA

Not septic: o Await sterile culture results to guide treatment

DURATION 4-6 weeks Shorter courses could be considered if the infected bone has been appropriately debrided

ALTERNATIVES FOR ALLERGIES If septic: meropenem 1 g iv q8h (penicillin cross-reactivity is ~ 1%) +/- vancomycin Not septic: await sterile culture results to guide treatment

TOP ORGANISMS Staphylococcus aureus Streptococci Gram negative bacilli Anaerobes

IMMUNOCOMPROMISED HOST CONSIDERATION

Same as for immunocompetent host

ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS X-ray be normal for the first 2 weeks of osteomyelitis; use CT or MRI for diagnosis if suspicion is high but x-ray

is negative





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COMMUNITY- ACQUIRED MENINGITIS

EMPIRIC CHOICE ceftriaxone 2 g iv q12h + vancomycin 25mg/kg iv loading dose x1 followed by 15 mg/kg iv q8h if over age 50, add ampicillin 2g iv q4h or TMP-SMX 5 mg/kg iv q6h

DURATION

S. pneumoniae: 10 days N. meningitidis: 7 days L. monocytogenes: 21 days

CONSULT

ID

ALTERNATIVES FOR ALLERGIES For non-anaphylactic penicillin allergy, ceftriaxone may be used. For severe β-lactam allergy, use moxifloxacin 400 mg iv q24h + vancomycin 15 mg/kg iv q8h (add agent for

Listeria if over age 50 or immunocompromised (see below)).

TOP FIVE ORGANISMS (what we expect for common organisms) S. pneumonia N. meningitidis L. monocytogenes (esp. in those over age 50) aerobic Gram-negative bacilli

CURRENT RESISTANCE ISSUES

The rate of ceftriaxone-resistant pneumococci in Toronto is <1%. Recommendations for treating with vancomycin are based, primarily, from jurisdictions with higher resistance than we are currently encountering in Toronto.

IMMUNOCOMPROMISED HOST CONSIDERATION (INCLUDING THOSE WITH ADVANCED LIVER/KIDNEY DISEASE)

Add ampicillin 2 g iv q4h or TMP-SMX 5 mg/kg iv q6h for Listeria coverage. Fungal meningitis (esp. cryptococcal) is relatively common in those with severe cell-mediated

immunocompromised (eg. steroids, transplantation).

ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS Dexamethasone 10mg iv q6h for 4 days (started as soon as possible prior to initiating antimicrobial therapy) is

currently recommended. The current evidence demonstrates that this neither provides benefit nor harm in patients with bacterial meningitis (vis a vis mortality, neurologic sequelae), but a single study from the Netherlands suggested benefit and the recommendation remains controversial.

Consideration for repeat lumbar puncture should be given for patients failing to improve after 24-48h of therapy.

References:

Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39(9):1267-84. Epub 2004/10/21.

de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347(20):1549-56. Epub 2002/11/15.

van de Beek D, Farrar JJ, de Gans J, Mai NT, Molyneux EM, Peltola H, et al. Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data. Lancet Neurology. 2010;9(3):254-63. Epub 2010/02/09.





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NOSOCOMIAL

MENINGITIS 1 PREFACE 2 Infectious Diseases consultation strongly recommended for all cases of nosocomial meningitis 3 4 EMPIRIC CHOICES

5 Vancomycin 15-20 mg/kg iv q12h (with loading dose) PLUS one of: 6 o ceftazidime 2 g iv q8h (or ceftriaxone 2 g iv q12h if basal skull fracture) 7 Adjunctive dexamethasone NOT routinely recommended 8 9

ROUTE

10 Intravenous (may consider p.o. step-down in cases caused by GNB susceptible to quinolones or TMP-SMX)

11

12

DURATION

13

Duration depends on multiple factors: 1) pathogen, 2) presence and removal of CSF shunt device, 3) presence

14

of brain abscess, 4) presence of skull bone involvement (i.e., osteomyelitis), 5) clinical response to therapy

15

o Meningitis

16

S. aureus – 14 days

17

Coagulase-negative staphylococci (CNST) – 7 days

18

Gram-negative bacilli – 21 days

19

o Shunt infection – Device removal almost always required for clearance of organisms

20

CNST – 7 days minimum, continue 7 days beyond shunt removal

21

S. aureus – 14 days

22

GNB – 21 days

23

24

ALTERNATIVES FOR ALLERGIES

25

If severe beta-lactam allergy, vancomycin PLUS one of: ceftazidime or anti-pseudomonal quinolone

26

27

MOST COMMON ORGANISMS

28

Staphylococcus species (including MSSA, MRSA and CNST)

29

Pseudomonas aeruginosa

30

Enteric gram-negative organisms (including broad-spectrum beta-lactamase producing organisms)

31

Propioinibacterium acnes

32

Organisms associated with community-associated acute bacterial meningitis far less common

33

34


35

Local rates of ESBL and AMP-C producing organisms important in determining whether a carbapenem is

36

indicated as initial therapy

37

38


39

Pathogens associated with community-associated bacterial meningitis also a consideration

40

Consider addition of Listeria coverage (i.e., ampicillin or TMP-SMX) to empiric therapy

41

42

ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS

43

Diagnosis based on clinical setting, CNS imaging, and cerebrospinal fluid (CSF) analysis (e.g., culture and cell

44

counts)

45

Organisms often considered to be non-pathogenic can be significant in nosocomial meningitis (e.g., CNST)

46

Intra-ventricular antibiotics of unclear benefit and may be considered in cases with persistently positive CSF

47

cultures or inability to remove CNS device

48

49

References:

50

Van de Beek D, Drake JM, & Tunkel AR. N Engl J Med. 2010; 362:146-154

51

52

Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, & Whitley RJ. Practice Guidelines for the Management of Bacterial

53

Meningitis. Clinical Infectious Diseases. 2004;39:1267 -1284

54

CONSULT

ID





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DIABETIC FOOT INFECTIONS

CONSIDER CONSULTING:

ID, Vascular Surgery, +/-

Plastic Surgery

*ID consultation recommended for mod-severe or complicated infections

EMPIRIC CHOICES Not infected – Do not treat (not all foot ulcers in diabetics are infected and absence of purulence or other

features of inflammation make infection unlikely) Cellulitis (without ulcer) – cefazolin 1 g iv q8h or cephalexin 500 mg p.o. QID Mild to Moderate – cefazolin 1-2 g iv q8h or cephalexin 500 mg p.o. QID Severe – several options, choice depends on concern for MDR pathogens; choose one of following:

o ceftriaxone + metronidazole o piperacillin-tazobactam 4.5 g iv q8h +/- vancomycin o meropenem +/- vancomycin o NB: vancomycin can be discontinued if patient is not colonized with MRSA

Chronic – usually requires more formal evaluation to allow targeted therapy, ID consultation recommended

ROUTE Initial therapy intravenously if moderate to severe, oral step-down if improving and reliable oral option

DURATION Duration guided by clinical response, with shorter courses being sufficient for quick to respond infections

o Cellulitis – 5-7 days o Mild to Moderate – 5-14 days o Severe – 7-14 days o Underlying osteomyelitis – 6 weeks

DOSAGE ADJUSTMENTS Concurrent renal disease is common, dosage adjustments depend on antimicrobial agent Higher doses (e.g., cefazolin 2 g q8h or cephalexin 750-1000mg p.o. qid) may be required for patients with

elevated BMI (≥ 30)

MOST COMMON ORGANISMS

Mild to Moderate o S. aureus, β-hemolytic streptococci

Severe or Chronic o Gram-positives (e.g., S. aureus, β-hemolytic streptococci), Gram-negatives, anaerobes o Increased risk for resistant pathogens (e.g., MRSA, P. aeruginosa, MDR gram-negatives)

CURRENT RESISTANCE ISSUES Patients with chronic infections and multiple prior courses of antibiotics are more likely to have polymicrobial

infections Patients colonized with resistant organisms (e.g., MRSA, ESBL/AMP-C producers) may require coverage for

these pathogens; however, these organisms may simply colonize wound rather than cause infection

IMMUNOCOMPROMISED HOST CONSIDERATION Similar empiric coverage

ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS Superficial swabs of wound are NOT recommended and are prone to contamination with colonizing organisms When possible, sterile wound cultures should be obtained prior to starting antibiotics when multiple pathogens

or osteomyelitis is suspected Imaging to confirm osteomyelitis – foot X-ray; MRI or bone/gallium scan if inconclusive; CT imaging may also

be of benefit Management includes multidisciplinary approach: wound care and debridement as needed, pressure off-

loading, chiropody, improved glycemic control, formal vascular evaluation of limb (+/- Vascular Surgery assessment)

Infections in those with poor vascular supply may have higher rates of treatment failure with Abx alone





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References:

Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012;54:e132-73.

Craig J, Moayedi Y, & Bunce PE. A purulent foot ulcer in a man with diabetes mellitus. CMAJ 2013; 185:579-80.


DIABETIC FOOT INFECTIONS




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Consult ID in cases of severe, complicated, or multiply recurrent CDI.

EMPIRIC CHOICE Step 1: Stop any unnecessary antimicrobials. Step 2: Empiric antimicrobial selection depends on severity of infection (Table 1).

ROUTE / DOSE

Clinical Definition Supportive Clinical Data Recommended Treatment

Initial episode, mild/moderate

No features of severe CDI.

metronidazole 500 mg p.o. TID x 14 days (alternatively 250 mg p.o. QID if GI intolerance).

Initial episode, severe

Leukocytosis with a wbc ≥ 15, or a SrCr ≥ 1.5x’s premorbid level.

vancomycin 125 mg p.o. 4 times daily x 14 days.

Initial episode, severe, complicated

Hypotension or shock, ileus, megacolon

vancomycin 125 mg p.o./ng 4 times daily PLUS metronidazole 500 mg iv every 8 hours. If complete ileus consider adding intra colonic vancomycin.*£ Consult ID and Surgery

First recurrence€ Same as initial episode, mild/moderate#

Second recurrence€

vancomycin in a tapered/pulsed regimen. Table 1. Recommendations for the Treatment of CDI (Adapted from Table 3 Infection Control & Hospital Epi. May 2010:31(5)).

* Early surgical intervention is key. Intracolonic vancomycin in to be considered last line adjunctive therapy only. £ Solution is supplied by pharmacy as 5 grams in 100 mL amber plastic or glass bottle (Final concentration of 500 mg per 10 mL). Each dose of 500 mg = 10 mL must be

further diluted as instructed in the administration section. See UHN Nursing administration policy for intra colonic vancomycin. € Consider referral to fecal transplant study. # Some experts prefer vancomycin, but the choice to do so must also consider the high cost of the drug (especially to those being discharged from the hospital) and the

lack of evidence supporting vancomycin over metronidazole in this setting.

DURATION For most cases, 14 days of therapy is adequate however, longer durations may be required for

severe or recurrent infection. This decision should be made in consultation with infectious diseases.

ALTERNATIVES FOR ALLERGIES Consult ID

IMMUNOCOMPROMISED HOST CONSIDERATION Except for instances of febrile neutropenia, treatment of CDI in immunocompromised hosts is not

automatically considered ‘complicated’. Patients should be assessed on a case by case basis based on risk factors and disease severity. Consult infectious diseases.

ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS Early surgical intervention should be considered in cases of severe CDI. There is no evidence to support test for cure by repeating C. difficile testing. Spores may remain for some

time and consequently C. difficile test may remain positive 6-8 weeks or longer in some cases. Avoid antiperistaltic agents. Avoid proton pump inhibitors unless indicated. There is no evidence to support long term antimicrobial prophylaxis for CDI.

Clostridium difficile (CDI)





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References Apisarnthanarak A, Razavi B, Mundy LM. Adjunctive intracolonic vancomycin for severe Clostridium difficile colitis: case series and review of literature. CID 2002;35:690‐96. Shen EP, Surawicz CM. The changing face of Clostridium difficile: What treatment options remain? Am J Gastroenterol 2007;102:2789‐91. Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Pepin J, Wilcox MH. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of Am erica (IDSA). Infect Control Hosp Epidemiol 2010;31:431‐55.

Clostridium difficile (CDI)





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Antibiotic Prophylaxis in Upper GI Bleeding

1 EMPIRIC CHOICE 2

ceftriaxone 3 4

5 6 ROUTE 7

iv 8 9 10 11 DOSE 12

1g 13 14 15 16 DURATION 17

3 days 18 19 20 21 ALTERNATIVES FOR ALLERGIES 22

ertapenem 1g iv daily 23 24 25 TOP FIVE ORGANISMS (what we expect for common organisms) 26

Enterobacteriaceae (responsible for ~80% of infections) 27 28

CURRENT RESISTANCE ISSUES 29 Many patients have been exposed to fluoroquinolones, and so there is a significant risk of quinolone-resistant 30

enterobacteriaceae in such patients. 31 32 33 ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS 34

Although not definitive, the burden of evidence demonstrates a benefit of antibiotic prophylaxis in upper GI 35 bleeding in patients with cirrhosis (and presumed variceal bleeding). However, the benefit is seen in all patients 36 with cirrhosis, regardless of the presence or absence of ascites. 37

Antibiotic prophylaxis appears to reduce bacteremia, pneumonia, SBP and urinary tract infections in this setting. 38 Many references recommend 2 g of ceftriaxone. The evidence does not support the need for this. 39

40 41 References: 42 43 Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Prevention and management of gastroesophageal varices and variceal 44 hemorrhage in cirrhosis. Hepatology. 2007;46(3):922-38. 45 46 Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila F, Soares-Weiser K, Mendez-Sanchez N, Gluud C, et al. Meta- 47 analysis: antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding - an updated Cochrane review. 48 Aliment Pharmacol Ther. 2011. 49 50





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Acute Exacerbation of COPD

1 Treatment of Acute Exacerbation of COPD with antimicrobials is controversial. The MSH-UHN ASP 2

does not endorse routine treatment of AECOPD with antimicrobials 3 4 However, if the decision to use antibiotics is made: 5 6 EMPIRIC CHOICE 7 ceftriaxone 1g iv daily or amoxicillin-clavulanate 875/125 mg p.o. BID 8 9 DURATION

10 7 days 11 12 ALTERNATIVES FOR ALLERGIES 13 moxifloxacin 400 mg p.o./iv daily 14 15 TOP FIVE ORGANISMS (what we expect for common organisms) 16 Streptococcus pneumoniae 17 Haemophilus influenzae 18 Moraxella catarrhalis 19 20 CURRENT RESISTANCE ISSUES 21 Consider the patients’ antibiotic exposure in the previous 3 months 22 Proportion of H.influenzae resistant to ampicillin/amoxicillin in 2008-20091: ~ 20% 23 Streptococcus pneumonia resistance rates from Ontario and Toronto labs 2010-20112: 24 o penicillin G (non-meningitis breakpoints) 0.4% 25 o ceftriaxone 0.7% 26 o moxifloxacin 1% 27 o levofloxacin 1.9% 28 o amoxicillin 4.5% 29 o doxycycline 16% 30 o azithromycin/clarithromycin 28% 31 32 IMMUNOCOMPROMISED HOST CONSIDERATION 33 None 34 35 36 References 37 38 Data courtesy of Dr.Donald Low from Ontario laboratories that submitted data to the Canadian 39 Bacterial Surveillance Network 40 41 Data courtesy of Dr.Allison McGeer from adult respiratory specimens from Ontario laboratories 42 participating in the CBSN/TIBDN, 2010-2011. 43 44

45





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Hospital-Acquired Pneumonia

1 EMPIRIC CHOICE 2

Patient is on a non-ICU ward: ceftriaxone 1g iv q24h or amoxicillin-clavulanate 875/125 mg p.o. BID 3 Patient is in the ICU or transferred there as a result of HAP: 4

o piperacillin-tazobactam 4.5 g iv q8h 5 o Could consider ceftriaxone instead of piperacillin-tazobactam for some patients in whom the risk of 6

Pseudomonas is likely low, such as patients who have been on a ward where Pseudomonas infections 7 are uncommon or those that have been in the hospital for ≤ 1 week 8

o If known to be colonized with MRSA, add vancomycin 9 o If known to be colonized with an ESBL, use meropenem 1g iv q8h instead of piperacillin-tazobactam 10

DURATION 11 7 days 12

13 ALTERNATIVES FOR ALLERGIES TO BETA-LACTAMS (see 1-pager on beta-lactam allergies for risk 14 of cross-reactivity) 15

Patient is on a non-ICU ward: moxifloxacin 400 mg p.o./iv q24h 16 Patient is in the ICU or transferred there as a result of HAP: 17

o moxifloxacin 400 mg p.o./iv q24h if infection due to Pseudomonas is likely to be low 18 o If Pseudomonas risk is high: meropenem 1 g iv q8h (cross-reactivity is 1% with penicillin allergy) 19 o If known to be colonized with MRSA, add vancomycin 20

21 TOP ORGANISMS (what we expect for common organisms) 22

Staphylococcus aureus 23 Gram negative aerobic bacilli (Klebsiella, Serratia, Pseudomonas, etc) 24 Streptococcus pneumoniae 25 Haemophilus influenzae 26

27 CURRENT RESISTANCE ISSUES 28

Consider the patient’s prior antibiotic use and colonization status (ie. ESBLs, MRSA) in making your empiric 29 decision 30

31 IMMUNOCOMPROMISED HOST CONSIDERATION 32

piperacillin-tazobactam 4.5 g iv q8h 33 Treat x 10 days 34

35 ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS 36

Antimicrobial therapy is not indicated for aspiration pneumonitis (primarily from macro-aspiration from vomiting). 37 Aspiration pneumonia (primarily from swallowing difficulties) does not require the addition of metronidazole as 38

the anaerobes involved are oral anaerobes (ie. Peptostreptococcus) which are covered by most beta-lactams 39





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EMPIRIC CHOICE Uncomplicated cellulitis (with or without abscess; includes erysipelas) : cephalexin 500 mg p.o. QID Complicated cellulitis (SSSI severe enough to cause hospitalization): cefazolin 1 g iv q 8 h Suspected CA-MRSA cellulitis (assessment based on risk factors):

o Uncomplicated: TMP/SMX DS 1 tab p.o. bid + cephalexin 500 mg po QID o Complicated: vancomycin 15 mg/kg iv q 12 h

Cellulitis in known MRSA colonized patient: as per MRSA susceptibility ROUTE

Uncomplicated cellulitis: oral Complicated cellulitis: intraveneous –if clinically improving, step down to oral after 24-48 hours

DURATION

Uncomplicated cellulitis: 5 days Complicated cellulitis: 7-10 days

ALTERNATIVES FOR ALLERGIES

Oral: Clindamycin or quinolone – TBA (as per LHIN document) IV: Vancomycin 15 mg/kg IV q 12 h

TOP FIVE ORGANISMS (what we expect for common organisms)

Group A Streptococci – more likely causative organism in non-purulent SSSIs Staphylococcus aureus – more likely causative organism in purulent SSSIs MRSA Other Streptococcus spp.


MRSA accounts for approximately 25% of all S. aureus isolates in Canada (CANWARD surveillance data) Avoid clindamycin in suspected CA-MRSA infections as risk of inducible resistance GAS remains 100% susceptible to penicillin


Gram negatives including Pseudomonas should be considered if not improving on standard Rx OR if ecthyma gangrenosum – add ciprofloxacin or change to ceftazidime

Consider fungal etiologies if associated skin lesions or if fail to respond to antibiotics after 1 week; suggest diagnostic biopsy

ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS

Blood cultures may assist management in immunocompromised and clinically unstable patients Abscess without surrounding cellulitis may be cured with lancing (I&D: send for C+S) alone and no antibiotics For non-resolving cellulitis or if concerned about exposure related cellulitis(ie. bites, water), consult ID

References:

IDSA SSSI guidelines Archives Int Med (JAMA Internal Medicine) 2004; 164(15): 1664-74 Diagn Microbiol Infect Dis 2011; 69(3): 320-5.

Skin and Skin Structure Infections (SSSIs)





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Central Line Infections

EMPIRIC CHOICE 1 Clinically stable short or long-term catheters: vancomycin 2 Septic patients: pip-tazo* 4.5 g IV q 8 h + vancomycin 3

4 ROUTE 5

Intravenous 6 7 DURATION 8

Generally 7-14 days, but dictated by organism and presence of complications. 9 o CNST in stable patient with short-term catheter: remove catheter and stop empiric vancomycin once 10

organism identified; monitor for clinical improvement 11 o CNST in patient with clinical line sepsis: remove catheter and continue vancomycin for 5 days 12 o Staphylococcus aureus infection in long-term catheter requires minimum 14 days therapy 13 o Complications such as infective endocarditis, suppurative thrombophlebitis or osteomyelitis require 14

prolongation of antibiotics to 4-6 weeks. 15 16 ALTERNATIVES FOR ALLERGIES 17

linezolid 600 mg iv/p.o. q 12h to replace vancomycin. Consult ID 18 19 TOP FIVE ORGANISMS (what we expect for common organisms) 20

Coagulase negative Staphylococci 21 Staphylococcus aureus 22 Enterococci 23 Candida albicans 24 Gram negative bacilli (including Pseudomonas aeruginosa in ICU and hemodialysis patients) 25


MRSA accounts for approximately 15% of S. aureus blood isolates 28 Gram negative susceptibility to pip-tazo in blood isolates from MSH/UHN ICUs 78-100%; aminoglycosides can 29

be considered as alternative 30 31 IMMUNOCOMPROMISED HOST CONSIDERATION 32

Consider adding gram negative coverage, including Pseudomonas aeruginosa, for empiric treatment of patients 33 with suspected line sepsis 34

Dialysis catheter-related infection: treat as immunocompromised. Dose accordingly. 35 36 ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS 37

The catheter must be removed and a new catheter inserted in a different location (if still needed) 38 If it will be difficult to remove catheter, consult ID 39 See Candidemia key messages for Candida CLIs 40

41 *Based on TGH, MSH, TWH ICU blood isolates antibiogram (all Gram negatives)

42 **Based on TGH hospital-wide non-urine isolates antibiogram (all Gram negatives)

43

44 References:

45

46 1. Mermel et al. Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related

47

Infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 49: 1-45.

48 2. Antibiograms – MSH, TGH, TWH; https://www.mountsinai.on.ca/education/staff-

49 professionals/microbiology/microbiology-laboratory-manual/antibiogram/copy_of_department-of-microbiology

50


https://www.mountsinai.on.ca/education/staff-professionals/microbiology/microbiology-laboratory-manual/antibiogram/copy_of_department-of-microbiology

https://www.mountsinai.on.ca/education/staff-professionals/microbiology/microbiology-laboratory-manual/antibiogram/copy_of_department-of-microbiology

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ɓ-Lactam Allergy

COOMBS AND GELL CLASSIFICATION OF HYPERSENSITIVITY REACTIONS1

Type Mediator Onset Clinical Reaction Comments

I Immediate and accelerated hypersensitivity

IgE antibodies < 1 hour (rarely 1-72 hours)

Anaphylaxis, urticaria, angioedema, hypotension, bronchospasm, laryngeal edema, pruritus

Anaphylaxis with penicillins: ~ 0.01-0.05% Anaphylaxis with cephalosporins: ~0.0001-0.1% Patients with anaphylaxis should not be given the offending drug again

II Delayed cytotoxic antibody-mediated hypersensitivity

IgG and IgM antibodies > 72 hours

Hemolytic anemia, thrombocytopenia, neutropenia

These reactions are drug specific, so the offending drug should be avoided in the future

III Antibody complex- mediated hypersensitivity

IgG and/or IgM complexes

> 72 hours

Serum sickness (fever, cutaneous eruptions, lymphadenopathy, arthralgias, myalgias), Glomerulonephritis Small vessel vasculitis Drug Fever

The antibody-antigen complexes can precipitate in tissues and potentially affect any end organ.

IV Delayed type hypersensitivity

T-cells > 72 hours Contact dermatitis Pustulosis

Incidence is low Eosinophilia, bullous exanthems and immune hepatitis may be due to T-cell activation as well

IDIOPATHIC REACTIONS1

Not clearly immune mediated Non-pruritic morbilliform and maculopapular rash (which occur in 3-7% of children that take amoxicillin) if

occurs, not a contraindication to taking the antibiotic again Stevens-Johnson Syndrome, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic

symptoms (DRESS) and erythema multiforme are rare with beta-lactams but because of the severity, the culprit antibiotic should be avoided

CROSS-REACTIVITY1

Between Penicillins and Cephalosporins o The widely cited risk of cross-reactivity between penicillins and cephalosporins of 8-10% is based on

studies from the 1970s and is now known to be flawed o Cross-reactivity between penicillin or amoxicillin and cephalosporins is due to similarities in side chains

so there will only be significant risk of cross-reactivity between those with a similar side chain at C-3 or C-7 (see Table below). For example, cefazolin is not expected to cross-react with any penicillin or cephalosporin as it does not have a similar side chain to any other beta-lactam, hence its absence from the table

Between Cephalosporins o Cross-reactivity amongst cephalosporins is low due to the significant heterogeneity of side chains (C-3

and C-7). o Therefore, if your patient has a cephalosporin allergy, you can safely prescribe another cephalosporin

that has dissimilar side chains (both C-7 and C-3 side chains must be different). Between Penicillins and Carbapenems

o Cross-reactivity is ~ 1%





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Table 1. Groups of cephalosporins and beta-lactams with similar C3 and C7 side chains1

Similar C-7 side chain. Cross reactions

between agents within one group is possible

Similar C-3 side chain. Cross reactions between agents within one group is possible

Group 1 Group 2 Group 3 Group 1 Group 2 Group 3 Group 4 Group 5 Group 6 Group 7 Penicillin Cephalothin Cefoxitin

Amoxicillin Ampicillin Cefaclor Cephalexin Cefadroxil

Cefepime Cefotaxime Ceftriaxone

Cefadroxil Cephalexin

Cefotetan Cefotaxime Cephalothin

Cefuroxime Cefoxitin

Cefixime Ceftazidime

REFERENCE 1. Lagace-Wiens P, Rubinstein E. Adverse reactions to beta-lactam antimicrobials. Expert Opin Drug Saf

2012;11:381-399.

ɓ-Lactam Allergy





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Empiric Use of Antifungals

1 SPECTRA OF ACTIVITY OF ANTIFUNGAL AGENTS (in alphabetical order): 2 Fungus Amphotericin B Fluconazole Posaconazole Voriconazole Echinocandins class

Aspergillus sp. + (± for A. terreus) - + + + Candida sp. + ± (C. krusei is resistant; dose-

dependent for C. glabrata) + + + (± for C.

parapsilosis) Cryptococcus sp. + + + + - 3 ANTIFUNGALS REGIMENS AVAILABLE INCLUDE: 4 Class Regimens (usual dosing) in alphabetical order by drug

Azoles Fluconazole 800 mg IV/PO daily Posaconazole† 200 mg PO Q6H for invasive fungal infections -200 mg PO TID for prophylaxis in GVHD

Voriconazole 6 mg/kg IV/PO Q12h x2 doses then 4 mg/kg IV/PO x2 doses for invasive aspergillosis

Echinocandins Anidulafungin† 200 mg Day 1 then 100 mg IV daily

Caspofungin 70 mg IV Day 1 then 50 mg IV daily

Micafungin† 100 mg IV daily

Polyenes Amphotericin B deoxycolate 0.5-1 mg/kg IV daily

Liposomal amphotericin 3 mg/kg IV daily --

†UHN only 5 For management of documented candidemia, please refer to “ASP Simple Messaging—Candidemia”. 6 7 IN WHOM SHOULD EMPIRIC ANTIFUNGALS BE CONSIDERED? 8

In critically ill patients, risk factors for candidemia are 9 o Intra-abdominal sepsis, especially if achievement of source control is uncertain 10 o Exposure to broad-spectrum antibiotics 11 o Presence of central venous catheter 12 o Total parenteral nutrition 13 o Renal replacement therapy 14 o Exposure to systemic corticosteroid and other cell-mediated immunosuppressive therapy 15

In febrile neutropenic patients, particularly in those with fever for longer than 4d despite appropriate empiric 16 antibiotics 17

18 SELECT INDICATIONS OF SPECIFIC ANTIFUNGALS: 19 Fluconazole: empiric treatment 20

in azole-naïve patients 21 in areas where C. albicans accounts for the majority of yeast isolates--MSH ICU and TGH CVICU 22

Voriconazole: empiric treatment of invasive aspergillosis 23 Posaconazole: 24

alternative to liposomal amphotericin and voriconazole in treatment of invasive aspergillosis 25 prophylaxis of invasive fungal infections in bone marrow transplant patients with GVHD 26

Echinocandins: 27 Empiric treatment of candidemia 28

o in azole-experienced (e.g. fluconazole prophylaxis) patients 29 o in areas where non-albicans yeast account for majority of yeast isolates—TWH ICU and TGH ICU 30

caspofungin is an alternative to voriconazole and L-AMB for invasive aspergillosis 31 Amphotericin B deoxycolate: alternative to azoles or echinocandins for candidemia 32 Liposomal amphotericin (L-AMB): 33

alternative to voriconazole in invasive aspergillosis due to progression of disease 34 alternative to amphotericin deoxycolate in those at risk of nephrotoxicity (age>50, concomitant nephrotoxic 35

agents, renal insufficiency at baseline) 36 treatment of invasive fungal infections involving the CNS 37

38 39





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ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS 1 Serum galactomannan twice weekly in high-risk febrile neutropenic patients as surveillance testing for invasive 2

aspergillosis 3 Bronchoscopy ideally within 72h of initiation of empiric antifungal (if not before) to obtain sample for staining and 4

fungal cultures, and to rule out other infections in those with suspected invasive aspergillosis. 5

References 6 Walsh TJ et al. Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society 7 of America. Clin Infect Dis 2008;46:327–60. 8 Pappas PG et al. Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious 9 Diseases Society of America. Clin Infect Dis 2009;48:503–35. 10 11 12 13 14





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Role of TMP-SMX

1 TMP-SMX is an excellent agent for susceptible organisms (eg. Enterobacter), with high oral bioavailability, high 2

tissue penetration (e.g. CNS, bone, soft tissues, lung) with a relatively low likelihood of C. difficile. 3

TMP-SMX is an excellent anti-staphylococcal agent, which can be used in staphylococcal skin and soft tissue 4 infections and staphylococcal pneumonia (incl. most MRSA) without accompanying bacteremia. 5

Because of resistance with Group A streptococci, TMP-SMX should not be used as monotherapy for non- 6 purulent cellulitis. 7

TMP-SMX has significant safety issues related to renal insufficiency, hyperkalemia and drug interactions in 8 older patients and those with chronic medical conditions (e.g. chronic kidney disease, DM, peripheral vascular 9 disease, etc.), especially when used in settings where patients cannot be carefully monitored (incl. upon 10 discharge). It should therefore be used with close monitoring in the elderly, those requiring prolonged 11 treatment, and/or those with diabetes, renal dysfunction, or haemotological disease. 12

The risk of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis is extremely low with TMP-SMX (~4.3 13 cases/million users in one week). However, it is 8-30 times higher than other antimicrobials. 14

TMP-SMX has significant drug interactions (eg. warfarin, oral hypoglycemic agents) 15

REFERENCE: 16 17 Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T, et al. Medication use and the risk of Stevens-Johnson 18 syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333(24):1600-7. 19

20

21 22 23 24 25





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Candidemia (Yeast)

EMPIRIC CHOICE

In non-neutropenic patients: fluconazole 800 mg once daily; if recent azole use or hemodynamically unstable, then an echinocandin

In neutropenic patients: amphotericin B liposomal 3 mg/kg iv once daily or an echinocandin

DURATION Repeat blood cultures at 48 hours after first cultures, and then at Day 4 and 7. 2 weeks after first negative blood culture + resolution of symptoms attributable to candidemia in absence of

metastatic complications

TOP FIVE ORGANISMS (what we expect for common organisms) C.albicans C.glabrata C.parapsilosis C.tropicalis C.krusei


Echinocandin not recommended for C.parapsilosis due to higher MICs C.glabrata should be empirically treated with echinocandin

IMMUNOCOMPROMISED HOST CONSIDERATION Amphotericin B liposomal 3 mg/kg iv once daily Fluconazole if less critically ill and no recent azole exposure Duration 2 weeks after resolution of neutropenia and last (+) blood culture and resolution of signs and

symptoms of infection Febrile patient with hematologic malignancy recovering from neutropenia at risk for hepatosplenic (chronic

disseminated) candidiasis (different treatment strategy) Transaminitis in the first week of therapy is unlikely due to fluconazole-associated toxicity

ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS ID consultation is strongly recommended (ID is always notified of blood cultures growing Candida) Remove all intravascular devices, replace if needed at different site Ophthalmology assessment to rule out ophthalmic disease within 1 week of therapy (or after count recovery in

neutropenic patient)

REFERENCES

1. Pappas et al. 2009. Candidiasis. Clin Inf Dis 48:503 2. Disseminated candidemia. 2013. Sanford Guide. Antimicrobial Therapy, Inc. Sperryville, VA.





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Influenza A and B

1 EMPIRIC CHOICE 2

Treatment (to be started within 48 hours of symptom onset): 3 o Standard dose: oseltamivir 75 mg p.o./ng twice daily x 5 days. 4

5 ROUTE 6

p.o./NG/PEG 7 8 DOSE 9

Renal dysfunction (CrCl < 30mL/min) 75 mg daily 10 Hemodialysis: 75 mg daily post dialysis on dialysis days 11 Children ≥ 12 months: > 40 kg 75 mg/dose p.o. BID 12 Obesity: No specific dosage adjustment indicated 13

14 DURATION 15

Treatment: 5 days 16 Prophylaxis: Consult ID or Infection Prevention & Control 17

18 ALTERNATIVES FOR ALLERGIES 19

None 20 21 TOP FIVE ORGANISMS 22

Influenza A and B 23 24 CURRENT RESISTANCE ISSUES 25

Consult ID as known or suspected drug resistance should be handled on a case by case basis. 26 Intravenous zanamivir (Special Access Program only) is the treatment of choice for patients who develop 27

prolonged acute influenza illness despite appropriate treatment with oseltamivir, or in some cases of 28 documented resistance to oseltamivir. 29

IMMUNOCOMPROMISED HOST CONSIDERATION 30 Immunocompromised hosts (e.g., SOT, HSCT, leukemia) need to be regarded as an especially vulnerable 31

group. 32 As early signs of influenza may be masked by symptoms associated with underlying disorders or their 33

treatment, treating such patients should done with a high level of suspicion for influenza virus infection and be 34 especially vigilant for the rapid development of oseltamivir resistance. 35

Duration of therapy should be determined in conjunction with ID. 36 37 ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS 38

If clinical suspicion remains high for a diagnosis of influenza despite a negative NP swab, a bronchoscopy 39 should be performed to obtain a lower respiratory tract sample and empiric therapy with oseltamivir may be 40 continued until this result becomes known. If both NP swab and bronchoscopy specimen results are negative 41 for influenza, it is reasonable to consider stopping oseltamivir therapy. 42

There is no clinical or virological advantage with oseltamavir 150mg twice daily compared with standard dose in 43 patients with severe influenza admitted to hospital. 44 45

46





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Double vs. Single Coverage in Management of Pseudomonas

aeruginosa Infections

EMPIRIC CHOICE: 1 Choice of antibiotic regimen should be guided by prior exposure and local susceptibility data. 2 Antibiotic regimens active against P. aeruginosa at MSH and UHN include: 3

piperacillin-tazobactam 4.5 g iv Q6H 4 Ceftazidime 2 g iv Q8H 5 Meropenem 1g iv Q8H (exception: CNS infection—Consult ID) 6 Aminoglycosides: gentamicin or tobramycin 5 mg/kg IV daily; amikacin 15 mg/kg IV daily 7 Ciprofloxacin 400 mg iv Q8H or 750 mg p.o. Q12H 8

9 DOUBLE VS. SINGLE COVERAGE 10

In patient care areas where P. aeruginosa susceptibility is high, routine double coverage with anti-pseudomonal 11 agents is not warranted. 12

Multi-drug resistant (MDR) P. aeruginosa is associated with prior antibiotic exposure. 13 During critical illness (e.g. septic shock) and in those vulnerable to severe infections due to 14

immunocompromised state, “upfront” double anti-pseudomonal coverage may improve the probability of having 15 at least one active regimen until susceptibility is known. Most commonly studied regimens include an 16 antipseudomonal beta-lactam plus an aminoglycoside. 17

MSH-UHN Ventilator-Associated Pneumonia algorithm recommends the addition of an aminoglycoside 18 (gentamicin or tobramycin) to a beta-lactam agent (piperacillin-tazobactam or meropenem) in patients with 19 septic shock. 20

Link: http://www.antimicrobialstewardship.com/sites/default/files/msh-uhn_vap_algorithm_0.pdf 21 High Risk Febrile Neutropenia Protocol for Malignant Haematology patients recommends gentamicin plus 22

piperacillin-tazobactam combination empirically for up to 72 hrs. Empiric therapy for febrile neutropenic patients 23 should always have activity against P. aeruginosa. 24

Link: http://www.antimicrobialstewardship.com/sites/default/files/asp_fn_protocol_secured_edition.pdf 25 Once susceptibility is known for the P. aeruginosa isolate, antibiotic therapy should be de-escalated to 26

monotherapy accordingly, and at adequate dosing. Ongoing double coverage has not been supported in 27 clinical trials, and may have been associated with adverse events such as nephrotoxicity. 28


Local P. aeruginosa susceptibility data (courtesy of Dr. Sue Poutanen) should be used to determine the most 31 appropriate empiric approach: 32

Site ( Date: Jan 1 2011-Dec 31, 2011) Specimen

source TG ICU TW ICU MSH ICU PMH (all units*)

Respiratory

Tobramycin ; amikacin: ≥80% susceptible

Meropenem; piperacillin-tazobactam: 70-79%

Gentamicin; ciprofloxacin: <70%

All regimens: ≥80% susceptible

Piperacillin-tazobactam; tobramycin; amikacin: ≥80%

Rest of alternatives: 70-79%

ALL regimens: ≥80% susceptible EXCEPT ceftazidime (74%)

Blood No isolates All regimens: ≥80%

susceptible Piperacillin-tazobactam;

amikacin: 100% Rest of alternatives: ≤69%§

All regimens: ≥80% susceptible EXCEPT ceftazidime (75%)

*To be interpreted with caution as it included all oncology patients and not just those with malignant haematological diseases, who 33 may have higher risk of MDR P. aeruginosa due to frequent antibiotic exposure. 34 §To be interpreted with caution—based on a small number of isolates 35 36 IMMUNOCOMPROMISED HOST CONSIDERATION 37

Upfront double coverage may improve the probability of adequate empiric therapy, but once susceptibility is 38 known, antibiotic regimen should be de-escalated to monotherapy accordingly. See also above comments on 39 High Risk Febrile Neutropenia Protocol. 40

41



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1 REFERENCE: 2 Tamma PD, Cosgrove SE and Maragakis LL. Combination therapy for treatment of infections with gram-negative 3 bacteria. Clin Microbiol Rev 2012;25:450. 4

5

6 7 8





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S. aureus BACTEREMIA

CONSULT ID

1 EMPIRIC CHOICE 2

vancomycin 15 mg/kg iv q12h (targeting ~15ug/mL trough) 3 cloxacillin 2 g iv q4h if known MSSA or patient known to be MRSA-negative 4

5 DURATION 6

14 days minimum. The decision to treat for longer is controversial. We currently recommend 28 days unless a 7 TTE is normal OR a TEE is negative for infective endocarditis. 8

9 ALTERNATIVES FOR ALLERGIES 10

vancomycin 11 daptomycin (if cannot administer β-lactam and vancomycin) 12


Approximately 25% of community-acquired isolates of S. aureus are methicillin-resistant. MRSA bacteremia is 15 uncommonly acquired in hospitalized patients at MSH and UHN who are known to be MRSA-negative. 16

Patients with MRSA bacteremia with a high-vancomycin MIC (≥2 ug/mL) should be referred to ID. They are 17 associated with worse clinical outcomes/higher failure rates than patients with a low MIC. In addition, patients 18 with MSSA with a high-vancomycin MIC are also associated with worse clinical outcomes, even when treated 19 with β-lactams. Additionally, no drug has been shown to be superior to vancomycin for MRSA. 20

21 IMMUNOCOMPROMISED HOST CONSIDERATION 22

None relevant 23 24 ADDITIONAL DIAGNOSTIC AND THERAPEUTIC COMMENTS 25

ID consultation is strongly recommended in most situations (ID is always notified of blood cultures growing S. 26 aureus). 27

If line-associated, the venous catheter should be removed. 28 Repeat blood cultures at 48h to demonstrate sterilization of blood. 29 Patients on vancomycin should have Therapeutic Drug Monitoring (TDM) instituted. 30 Approximately 20% of catheter-associated SAB is associated with infective endocarditis. 31 Daptomycin should be considered if patients are failing vancomycin therapy. 32 We do not recommend use of a second agent (e.g. aminoglycoside or rifampin) for SAB 33

34 REFERENCES: 35

1. Holmes NE, Turnidge JD, Munckhof WJ, Robinson JO, Korman TM, O'Sullivan MV, et al. Antibiotic Choice May 36 Not Explain Poorer Outcomes in Patients With Staphylococcus aureus Bacteremia and High Vancomycin 37 Minimum Inhibitory Concentrations. J Infect Dis. 2011;204(3):340-7. 38

2. van Hal SJ, Lodise TP, Paterson DL. The clinical significance of vancomycin minimum inhibitory concentration 39 in Staphylococcus aureus infections: a systematic review and meta-analysis. Clin Infect Dis. 2012;54(6):755-71. 40

3. van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB. Predictors of mortality in 41 Staphylococcus aureus Bacteremia. Clin Microbiol Rev. 2012;25(2):362-86. 42

4. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the 43 infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections 44 in adults and children. Clin Infect Dis. 2011;52(3):e18-55. 45





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