7th Oncology review Course on April 24-25, 2013 in Intercontinental Hotel, Jeddah

Mansoor Ahmed KhanB.Pharm, MS, BCOP

Clinical Pharmacist Adult Oncology/HemKAMC-WR Jeddah

Bugs and Drugs: Antimicrobials use in Cancer Patients

Do Bugs need Drugs in immunocompromized Cancer

patients

Introduction. Classification of Bacteria Normal Bacterial Flora MDRs Classification of Antibiotics Most common bugs and Abx Options Common infections in Oncology patients Febrile Neutropenia

Outlines

Gram-positive bacteria retain the stain, and hence appear purple or blue-black when visualised by bright-field microscopy.

Gram-negative bacteria cannot retain the dye complex, and need to be counterstained with a red dye such as carbol fuchsin before they can be seen in the bright-field microscope.

The shape of bacteria is also used to classify them. Bacteria display three basic shapes: round (cocci, from the Greek kokkos - a berry), rod shaped (bacilli, from the Latin bacillus - a stick or rod), or spiral.

Bases of Bacterial Classification

Gram Positive Cocci1. Staphyllococci (Clusters)2. Streptococci (Chains)3. Pneumococci Gram Positive Bacilli1. The genus bacillus2. Clostridia3. Other Gram Positive Bacilli- Listeria,

Corynebacterium

Classification of the Bacteria

GPC in Cluster: Staph

GPC in Chains: Streptococci

VRE

Gram Negative Cocci 1. Neisseria Gram Negative Bacilli1. Enterobacteriaceae- Major Class2. Pseudomonads3. Curved Gram Negative Rods4. Cocco-bacilli5. Other Gram Negative Bacilli- Legionella

Classification of the Bacteria

E.Coli

Pseudomonas Aeruginosa

Staphyllococci1. MSSA, MRSA2. MSSE- Coagulase Negative Staph, MRSE3. VRSA, VRSE Streptococci1. Non-Hemolytic Streptococci (Enterococci,

E.fecalis VSE, VRE)2. Hemolytic Streptococci

α-hemolytic streptococci (S.pneumonia, S.viridans) β-hemolytic streptococci (Group A, B,C,D, G)

(S.pyogenes)

Gram Positive Cocci

Bacillus (spore forming)B.anthracis (Anthrax), B.cereus

ClostridiaC.Difficile (diarrhea), C.perfringes (gangrene), C.botulinum (Botulism)

Other Gram Positive Bacilli Listeria (Meningitis), Corynebacterium (Diphtheria), Propionibacterium acne

Gram Positive Bacilli

Neisseria (Diplococci)

Neisseria meningitidis is an important cause of bacterial meningitis

Neisseria gonorrhoeae causes gonorrhoea.

Gram Negative Cocci

Gram Negative Bacilli

Enterobacteriaceae1. E.Coli2. Klebsiella3. Salmonella4. Shigella5. Proteus6. Yersinia7. Citrobacter8. Enterobacter9. Morganella10. providentia

PseudomonadsP.Aeruginosa

Curved GN- Rods Vibrio Campylobacter H.Pylori

Contd Gram Negative Bacilli

Cocco-bacilli Moraxella Acinetobacter Haemophilus

H.Influenza H.Parainfluenza

Others Legionella Bordetella Bartonella Stenotrophomonas

Obligatory GN Anaerobes

1. Bacteroids

Anaerobes

Gram +ve Anaerobes

Gram Positive Cocci1. Peptococcus Spp2. Peptostreptococcus Spp Endospore forming GPB1. Clostridium Non-spore forming GPB1. Actinomyces Spp2. Eubacterium3. Propionibacterium

Gram -ve Anaerobes Gram negative Bacilli1. Bacteroides fragilis2. Other Bacteroides Spp3. Fusobacterium

Gram Negative Cocci1. Neisseria meningitidis2. Neisseria gonorrhoeae3. Veillonella

Miscellaneous

Chlamydia 1. C.trachomatis (STD)2. C.pneumonia (Live Stock)3. C.psittaci (Birds)

Riscketsia1. R.prowazekii2. R.ricketsii

Spirochaetes (STD)1. Treponema pallidum

(Syphilis)

2. T. pallidum pertenue (Yaws)

Mycoplasma Pneumonia

AFB1. MAC2. M.kansasii3. M.leprae4. M.tuberculosis

Normal Bacterial Flora

Skin Staphylococci and Corynebacterium

Conjunctiva Sparse, GPC and GNB

Oral Cavity Streptococci and Lactobacillus

Nasal Staphylococci and Corynebacterium

Pharynx Strept, Neisseria, GNB and GNC

Stomach H.Pylori (Upto 50%)

Normal Bacterial Flora

Small Intestine

Lactics, Enterics, Enterococci

Colon Bacteroides, Lactics, Enterics, Enterococci, Clostridia

Ant Urethera Sparse, Staphylococci, Corynebacterium, Enterics

Vagina Lactic during child bearing age otherwise mixed flora.

Multidrug Resistant pathogens

Gram +ve1. MRSA2. VRSA3. VISA4. MRSE5. VRE

Gram –Ve1. Pseudomonas2. Xanthomonas or

Stenotrophomonas3. Acinetobacter4. ESBL Inducers

(Klebsiella + E.Coli + 1-3 in KKH)

Classification Of Antibiotics

CW synthesis Inhibitor

1. Penicillins2. Cephalosporins3. Carbapenems4. Glycopeptide Folate Antagonist1. Sulfonamides

Protein synthesis Inhibitor

1. Tetracyclines2. Aminoglycosides3. Macrolides-Lincosamide4. Streptogramins5. Chloramphenicol DNA Gyrase Inhibitors1. Fluroquinolones

Penicillin

Penicillins Penicillin G Penicillin V Antistaphyllococcal Cloxacillin Flucloxacillin Methicillin Oxacillin Nafcillin

Extended Spectrum1. Amoxicillin2. Augmentin3. Ampicillin4. Unasyn Antipseudomonal1. Piperacillin2. Tazocin3. Ticarcillin4. Timentin

Strept, GPB, Anaerobes

Staph, Strept, H.pylori , E.Coli,

Klebsiella , Salmonella, Anaerobes

Enterobacteriaceae, PSEAER, Anaerobes,

Staph, Strept

Cephalosporins

1st Generation Cefazolin Cefalexin 2nd Generation Cefuroxime Cefprozil Cefaclor Cefonicid Cefoxitin Loracarbef Cefotetan

3rd Generation Cefotaxime Ceftriaxone Ceftazidime Cefpodoxime Cefixime 4th Generation Cefepime Cefoperazone 5th Generation Ceftaroline

MSSA, Strep, E.Coli, Proteus

Klebsiella, H.Infleunza, Moraxella, Morganella

MSSA, Strep, E.Coli,

Klebsiella, H.Infleunza,

Proteus

ACIBAU, Citrobacter, Enterobacter

, Serratia, Pseudomona

s, Salmonella

Gram +ve ,

Gram -ve, PSEAER

MSSA, MRSA, Gram –Ve but

no PSEAER coverage

Carbapenems Imipenem Meropenem Doripenem Ertapenem Biapenem PZ-601

Monobactams Aztreonam

Carbapenems & Monobactams

MSSA, Strept, ACIBAU, PSEAER, Citrobacter, Enterobacter, ESBLs,

Klebsiella, E.Coli, H.Infleunza, Proteus, Serratia, Anaerobes,

Same as Carbapenems but no

Gram Positive Coverage and no

ACIBAU

Vancomycin Teicoplanin

Glycopeptides

MSSA, MRSA, VSE, CNSTA, Streptococci, Diptheroids

Daptomycin

Lipopeptide

MSSA, MRSA, VSE, CNSTA, Streptococci, Diptheroids

Tetracycline OTC Demeclocycline Minocycline Doxycycline Tigecycline (Derivative of Minocycline and

broad spectrum. Covers G+ve and G-ve and MDR strains except PSEAER & Proteus)

Tetracyclines

ACIBAU, Anaerobes, Brucella,

Camplylobacter, Chlamydia,

Enterobacter, E.Coli, H.Influenza, Listeria,

Mycoplasma, Shigella, Strept, Yersinia, Vibrio

Streptomycin Amikacin Gentamycin Tobramycin Neomycin (PO or Topical) Kanamycin (PO or Topical)

Aminoglycosides

Enterobacteriaceae, PSEAER,

ACIBAU

Macrolides and Related Agents-MLS

Macrolides1. Erytheromycin2. Clarythromycin3. Azithromycin

Clindamycin

Streptogramins Quinopristin-

Dalfopristine (synercid) MRSA, VRE

Oxazoladinones Linezolid MRSA,

VRE

Staph, Strept,

Atypical, H.influen

za, Moraxella

Staph, Strept,

Anaerobes

Sulfonamides

Sulfonamides Sulfamethoxazole Sulfapyridine Sulfadiazine Sulfisoxazol Sulfamethizole

Pyrimidines Trimethoprim (TMP) Pyrimethamine Fixed Combinations1. Septrin (SMZ+ TMP)

2. Fansidar (Sulfadoxine+ Pyrimethamine) Malaria

PCP, Stenotrophomon

as, Enterobacteriace

ae

Fluroquinolones

1st Generation1. Nalidixic Acid2. Norfloxacin3. Cinoxacin 2nd Generation1. Ciprofloxacin2. Levofloxacin3. Ofloxacin4. Lomefloxacin5. Enoxacin

3rd Generation Gatifloxacin Sparfloxacin 4th Generation Moxifloxacin

MSSA, Strept Enterobacteriace

ae

MSSA, Strept Enterobacteriace

ae, Atypical, Anaerobes

PSEAER, Atypical

MSSA, Strept Enterobacteriace

ae, Atypical, Anaerobes

WEAK Gram -

ve & Weak Gram +ve

Antimycobacterial Drugs

1st Line ATT INH Rifampin PZA Ethambutol Streptomycin

2nd Line ATT Amikacin Capreomycin Moxifloxacin Ciprofloxacin Levofloxacin PAS Ethionamide Cycloserine

Bacteriostatic Vs Bactericidal

Bacteriostatic1. Sulfonamides2. Tetracyclines3. Chloramphenicol4. Linezolid (except

streptococci)

Bactericidal1. Penicillins2. Cephalopsorins3. Glycopeptides4. Carbapenems5. Aminoglycosides6. Macrolides7. Fluroquinolones8. Sulfonamide +TMP

Treatment Options against Various Bugs

MSSA- Cloxacillin, Augmentin

MRSA- Vancomycin

VSE-Vancomycin

VRE-Linezolid

Pseudomonas- Tazocin, Amikacin Carbapenem, Cefepime, Ciproflox

Stenotrophomonas- Septrin

Acinetobacter- Colistin, Carbapenems, Tigecyclin

ESBL Inducers-Carbapenem

Anaerobes, Flagyl, Clindamycin

Atypical Pneumonia-Zithromax

PCP- Septrin

Enterobacteriaceae- Cipro, Moxi, Penicillins, Cephalosporins, Amikacin, Gentamycin

Listeria, Ampicillin

Site Specific Infections in Oncology

Meningitis Endocarditis URTI LRTI UTI Skin and soft tissue Intraabdominal

Pseudomembranous Colitis

Otitis Media CAP HAP Febrile Neutropenia

38

Definitions

Neutropenia: Absolute neutrophil count (ANC) < 500 cells/mm3 OR

expected to go <500 cells/mm3 during next 48hr

Profound Neutropenia: ANC <100 cells/mm3

Functional Neutropenia: impaired phagocytosis & killing of pathogens despite normal neutrophil count

Fever: Oral temperature measurement that is ≥ 38.30 C (1010 F) once ≥ 380 C (100.50 F) for > 1 hr

39

Common organisms

A recent prospective observational study involved > 2000 pts showed that only 23% of FN episodes associated with bacteremia

G+ve 57% > G-ve 34% > polymicrobial 9%

Mortality associated bacteremia G-ve > G+ve 18% vs 5%

P. aeruginosa coverage remains an essential component of initial empirical Abx regimen

Klastersky J et al. Bacteraemia in febrile neutropeniccancer patients. Int J Antimicrob Agents 2007; 30(Suppl 1):S51–9.Pizzo PA, et al. Empiric antibiotic and antifunga ltherapy for cancer patients with prolonged fever and granulocytopenia. Am J Med 1982; 72:101–11.Schimpff SC. Empiric antibiotic therapy for granulocytopenic cancer patients. Am J Med 1986; 80:13–20.

40

Mucositis- Common source of infection

www.pacificprosthodontics.com/.../ oncology.html

41

Infected Line

www.emedicine.com/ derm/topic770.htm

42

Risk Assessment, MASCC Score

Burden of febrile neutropenia with no or mild symptoms

5

No hypotension (systolic blood pressure>90 mmHg) 5

No chronic obstructive pulmonary disease 4

Solid tumor or hematologic malignancy with no previous fungal infection

4

No dehydration requiring parenteral fluids 3

Burden of febrile neutropenia with moderate symptoms

3

Outpatient status 3

Age < 60 years 2

43

Risk Assessment

High risk patient

Anticipated neutropenic period to last >7 days & profound neutropenia

Significant medical co-morbid condition

Should be hospitalized for empirical Abx.

MASCC score < 21

Anticipated neutropenic period to last ≤ 7 days

No or few comorbidities Candidate for oral &/or

outpatient empirical therapy

MASCC score ≥21

Low risk patient

44

45

Empiric Antibiotic Therapy

Monotherapy Broad spectrum, anti pseudomonal antibiotics

Piperacillin /tazobactam : 4.5gm IV q6h Carbapenem Imipenem/cilastatin : 500mg IV q6h Meropenem : 1gm IV q8h : 2gm IV q8h

(meningitis) Cefepime : 2gm IV q8h Ceftazidime : 2gm IV q8h

Need dose adjustment in renal patient

46

Empiric Antibiotic Therapy

For PCN allergic patient use either:

Ciprofloxacin + Clindamycin OR

Aztreonam + Vancomycin

Either combination will ensure anti pseudomonal and G +ve coverage.

47

Saudi Arabia National Guard - Health Affair

King Khalid National Guard Hospital

INTERNAL POLICY AND PROCEDURE (IPP)

Saudi Arabia National Guard - Health AffairKing Khalid National Guard Hospital

Clinical pathway : Febrile Neutropenia in adults patients .

Responding

Discontinue therapy after 48hr of neutropil recovery

NeutropeniaNo neutropenia

Continue IV therapy for 7days then Ciprofloxacin 500 mg PO q12

hr and Augmentin 625 mg PO q8hr

for 7 days

ID Consultation for Type and duration of

therapy

Documented infection

Fever of unknown origin

Not Responding

Blood culturesCT chest

Abelcet 5 mg/kg q24ID Consultation

Stable Deteriorating

Continue Tazocin Discontinue Amikacin

Do not add Vancomycin

Imipenem 500mg IV q6hr

Vancomycin 15mg/kg IV q12hr

Thanks and Questions

END

Bugs & Drugs Antimicrobial Reference 2012

Alison G. Freifeld et al. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases 2011;52(4):e56–e93

John’s Hopkins Antibiotics guide

References