Childrens Hospital Antibiogram for 2012 (Based on data from 2011)

Childrens Hospital Antibiogram for 2012 (Based on data from 2011) Prepared by: Department of Clinical Microbiology, Health Sciences Centre For further information contact: Andrew Walkty, MD, FRCPC Medical Microbiologist, Health Sciences Centre/Diagnostic Services of Manitoba or Daryl J. Hoban, PhD, D(ABMM), FCCM Clinical Microbiologist, Health Sciences Centre/Diagnostic Services of Manitoba 1

DISCLAIMERS This guide is provided as an educational resource for physicians and other healthcare professionals caring for patients at the Winnipeg Childrens Hospital. The authors of the guide have made every effort to ensure that the information contained in it was accurate at the time of publication. Users of the guide are encouraged to consult other references to confirm the information presented in it. The authors are not responsible for errors, omissions, inaccuracies, or the continued completeness of the information contained in the guide. The information in the guide should not be used or relied upon to replace the skill and professional judgment required to determine appropriate patient care and treatment. Also, the guide is not intended to replace or to be used as a substitute for the complete prescribing information prepared by each pharmaceutical manufacturer for their anti-infective agents. Because of possible changes in anti-infective indications, changes in dosage information, differences in patients responses to therapy, newly described toxicities, drug-drug interactions, and other items of importance, reference to complete prescribing information is recommended before any of the anti-infective agents described in the guide are used. HOW TO USE THE ANTIBIOGRAM PORTION OF THE GUIDE (Tables 1-6) The information presented in the antibiogram is intended only to guide initial empiric anti-infective agent therapy at the Winnipeg Childrens Hospital. Initial broad-spectrum empiric therapy should be focused to the most appropriate narrow-spectrum agent(s) based on the laboratory identification of pathogen(s) and known susceptibility patterns/results, if the situation permits. Consideration should be given to equally efficacious but less expensive antiinfective agents for empiric therapy or when streamlining of therapy is desired, if the situation permits. 2

Ampicillin Piperacillin Piperacillin- Tazobactam b Cefazolin Cefuroxime Ceftriaxone Ceftazidime Imipenem Amikacin Gentamicin Tobramycin Trimethoprim- Sulfamethoxazole Table 1. In vitro activity of selected anti-infective agents tested against Gram-negative bacilli a Organism (number tested): January through November 2011 Nitrofurantoin c = Not tested, not routinely reported, or not recommended a Enterobacter cloacae (76) 64 82 79 81 100 100 99 99 84 21 Escherichia coli (41) systemic 39 41 98 83 93 93 100 100 100 100 68 Escherichia coli (414) urine 50 50 98 90 98 99 100 100 97 96 72 98 Haemophilus influenzae (46) d 80 100 75 Klebsiella pneumoniae (32) 98 94 97 97 100 100 100 100 94 38 Pseudomonas aeruginosa (51) 96 96 96 98 98 90 98 Isolates tested and reported are from all sources combined, with the exception of Escherichia coli (subdivided into systemic isolates and urine isolates); isolates were collected from Jan to Nov, 2011 with the exception of Enterobacter cloacae and Haemophilus influenzae (collected from Jan 2010 to Nov 2011); data compiled according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI) in their document M39-A3 (2009). b Piperacillin-Tazobactam data obtained from the 2011 CANWARD study (Zhanel et al.). Local data not available related to a limitation in the method used for testing. c Nitrofurantoin is indicated for acute cystitis only. d For Haemophilus influenzae, only 43 isolates were tested for cefuroxime and 40 isolates were tested for trimethoprim-sulfamethoxazole. No data are available for Meropenem. 3

Penicillin Vancomycin Clindamycin Trimethoprim- Sulfamethoxazole Linezolid Nitrofurantoin e Table 2. In vitro activity of selected anti-infective agents tested against Gram-positive cocci a Organism (number tested): January through November 2011 = Not tested, not routinely reported, or not recommended Oxacillin b Erythromycin c Rifampin d Staphylococcus aureus (317) 57 100 57 89 97 100 100 99 Staphylococcus epidermidis (42) 17 100 9 24 70 100 100 100 Streptococcus pyogenes (n.a.) f 100 (Group A Streptococcus) Streptococcus agalactiae (148) g (Group B Streptococcus) 100 100 70 79 a b c d e f g Isolates tested and reported are from all sources (surveillance isolates excluded), Jan to Nov, 2010; data compiled according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI) in their document M39-A3 (2009). Oxacillin accurately predicts the activity of all semi-synthetic penicillins, including cloxacillin, beta-lactam/beta-lactamase inhibitor combinations, and cephalosporins for Staphylococcus aureus and coagulase-negative staphylococci. Erythromycin activity predicts the activity of azithromycin and clarithromycin for staphylococci and streptococci. Rifampin should NOT be used alone as treatment for infection. Nitrofurantoin is indicated for acute cystitis only. n.a. = not applicable Susceptibility testing of Streptococcus pyogenes is not routinely performed as 100% are susceptible to penicillin. If treating infection in a penicillin allergic patient, contact the lab for testing of second line agents. Data for Streptococcus agalactiae obtained from 148 vaginal/rectal isolates tested at the St. Boniface Hospital Microbiology Laboratory in 2003. 4

Penicillin (oral) Penicillin (intravenous) Ceftriaxone Vancomycin Clarithromycin Clindamycin Trimethoprim- Sulfamethoxazole Table 3. In vitro activity of selected anti-infective agents tested against Streptococcus pneumoniae isolates collected at the Health Sciences Centre, Winnipeg a Infection Type (number tested) = Not tested, not routinely reported, or not recommended HSC and SBH Data b Meningitis (66) 77 95 100 73 Non-Meningitis infection (66) 77 94 97 100 62 86 73 National Data b Meningitis (219) 84 98 100 79 Non-Meningitis infection (219) 84 97 99 100 77 94 79 a Isolates tested and reported are from all sources combined and patients of all ages (includes adults). National data were extracted from the 2010 CANWARD Study (Zhanel et al.). Health Sciences Centre (HSC) and St. Boniface Hospital (SBH) data were obtained by testing a random selection of Streptococcus pneumoniae isolates collected at HSC and SBH between January and December, 2010. b For Streptococcus pneumoniae, different susceptibility breakpoints for penicillin and ceftriaxone exist depending on whether meningitis or a non-meningitis infection is being treated [CLSI, M100-S19]. For penicillin, when treating a non-meningitis infection different breakpoints exist for oral and intravenous dosing. For non-meningitis infections, susceptibility to intravenous penicillin predicts susceptibility to amoxicillin. Oral agents are not appropriate for the treatment of bacterial meningitis. 5

Vancomycin Trimethoprim- Sulfamethoxazole Erythromycin Clindamycin Linezolid Table 4. In vitro activity of selected anti-infective agents tested against Methicillin Susceptible and Methicillin Resistant Staphylococcus aureus isolates a Organism (number tested) = Not tested, not routinely reported, or not recommended Oxacillin b Methicillin Susceptible Staphylococcus aureus (188) 100 96 77 85 Methicillin Resistant Staphylococcus aureus (128) 0 100 99 27 95 100 a Isolates tested and reported are from all sources (surveillance isolates excluded), Jan to Nov, 2011; data compiled according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI) in their document M39-A3 (2009). b Oxacillin accurately predicts the activity of all semi-synthetic penicillins, including cloxacillin, beta-lactam/beta-lactamase inhibitor combinations, and cephalosporins for Staphylococcus aureus. 6

Fluconazole Itraconazole Voriconazole Flucytosine Caspofungin Penicillin Amoxicillin- Clavulanate Piperacillin- Tazobactam Cefoxitin Clindamycin Imipenem Metronidazole Table 5. In vitro activity of selected anti-infective agents tested against anaerobic isolates collected at hospitals in Winnipeg a Organism (number tested) = Not tested, not routinely reported, or not recommended Bacteroides fragilis group (70) (includes Bacteroides fragilis) 81 100 56 49 100 100 a Isolates tested and reported are all from wound specimens (patients of all ages, including adults). Data were extracted from the ongoing CANAEROBES study (Zhanel et al.). Table 6. In vitro activity of selected anti-fungal agents tested against Candida species collected from hospitals in Winnipeg a Organism (number tested) Candida albicans (30) 100 100 100 97 100 Candida glabrata (30) 97 7 97 100 100 a Data obtained by testing a random sample of C. albicans and C. glabrata isolates from Health Sciences Centre and St. Boniface Hospital, collected between Jan 2008 and Dec 2009. Isolates tested and reported are from blood only (patients of all ages, including adults). 7

Table 7. Pediatric oral antimicrobial dosage guidelines Antibiotic Usual Dosages a,b Cost ($) per day c ANTIBACTERIAL AGENTS Penicillins Amoxicillin 25-50 mg/kg/day divided tid d 0.60 1.10 Amoxicillin/Clavulanate 25-50 mg/kg/day divided bid-tid e 2.10 3.10 Cloxacillin 50-100 mg/kg/day divided qid 0.80 1.50 Penicillin V 25-50 mg/kg/day divided tid-qid 0.30 Cephalosporins Cefprozil 15-30 mg/kg/day divided bid 2.25 4.50 Cephalexin 25-50 mg/kg/day divided tid-qid 0.9 1.80 Macrolides Azithromycin 5-10 mg/kg once daily 3.10 6.20 Clarithromycin 15 mg/kg/day divided bid 2.20 4.50 Erythromycin 30-50 mg/kg/day divided tid-qid 0.80 1.60 Others Clindamycin 10-30 mg/kg/day divided tid 3.30 5.00 Co-trimoxazole 6-12 mg/kg/day divided bid f 0.30 Nitrofurantoin 5-7 mg/kg/day divided qid 0.70 1.50 Trimethoprim 4-6 mg/kg/day divided bid 0.75 Metronidazole 30 mg/kg/day divided tid 0.35 ANTIFUNGAL AGENTS Fluconazole 3-12 mg/kg once daily 6.10 25.00 Itraconazole 3-10 mg/kg once daily 8.00 16.00 Ketoconazole 3.3-6.6 mg/kg once daily 1.30 2.70 ANTIVIRAL AGENTS Acyclovir 30-80 mg/kg/day divided 3-5x/day 5.00 16.00 Valacyclovir 60 mg/kg/day divided tid 8.00 16.00 a. Typical doses in infants and children. Maximum doses generally should not exceed typical adult doses. b. Does not reflect dosing in neonates; refer to Pediatric Drug Dosage Handbook (Lexicomp) for dosing information in this patient population. c. Approximate cost per inpatient day excluding dispensing costs as of February 2010 based on the Manitoba Drug Interchangeability Formulary and Manufacturer s List Prices. Prices have been rounded and are based on typical adult daily doses. d. Use 20-30 mg/kg/day divided bid in infants 3 months. e. Dosing based on amoxicillin component only f. Dosing based on trimethoprim component only 8

Table 8. Pediatric parenteral antimicrobial dosage guidelines Antibiotic ANTIBACTERIAL AGENTS Penicillins Ampicillin Cloxacillin Penicillin G Sodium Piperacillin ± Tazobactam Meropenem Cephalosporins Cefazolin Cefoxitin Cefuroxime Cefotaxime Ceftriaxone Ceftazidime Macrolides Azithromycin Aminoglycosides Gentamicin Tobramycin Others Clindamycin Co-trimoxazole Metronidazole Vancomycin ANTIFUNGAL AGENTS Amphotericin B Fluconazole ANTIVIRAL AGENTS Acyclovir Ganciclovir (induction doses) Usual Dosages a,b 100-200 mg/kg/day divided q6h 100-200 mg/kg/day divided q6h 100,000-250,000 units/kg/day divided q4-6h 200-400 mg/kg/day divided q6h c 30-120 mg/kg/day divided q8h 25-100 mg/kg/day divided q6-8h 80-160 mg/kg/day divided q6-8h 75-150 mg/kg/day divided q8h 100-200 mg/kg/day divided q6-8h 50-100 mg/kg/day divided q12-24h 100-150 mg/kg/day divided q8h 5-10 mg/kg q24h 4.5-7.5 mg/kg/day divided q8h d 4.5-7.5 mg/kg/day divided q8h d 25-40 mg/kg/day divided q8h 6-20 mg/kg/day divided q6-12h e 30 mg/kg/day divided q8h 40 mg/kg/day divided q6-8h 0.25-1 mg/kg q24h 3-12 mg/kg q24h 15-60 mg/kg/day divided q8h 10 mg/kg/day divided q12h a. Typical doses in infants and children. Maximum doses generally should not exceed typical adult doses. b. Does not reflect dosing in neonates; refer to Pediatric Drug Dosage Handbook (Lexicomp) for dosing information in this patient population. c. Dosing based on piperacillin component only. d. Dosing varies with patient age. Refer to Pediatric Drug Dosage Handbook (Lexicomp) or the Health Sciences Centre Pediatric Drug Dosage Handbook for more comprehensive dosing information. e. Dosing based on trimethoprim component only. 9

Drug Table 9. Pediatric dosing recommendations in renal impairment a Creatinine Clearance (CL CR) in ml/min/1.73 m 2b (suggested dosage adjustment based on normal dose) Supplement for Dialysis Penicillins Ampicillin >30 10-30 <10 (q6h) (q8-12h) (q12h) Cloxacillin NO CHANGE NECESSARY NO Penicillin >50 10-50 <10 (q4-6h) (75%) (20-50%) Piperacillin >50 20-50 <20 (q6h) (q8h) (q12h) Piperacillin/ > 50 30-50 <30 Tazobactam (q6h) (65% q6h) (50% q8h) Cephalosporins Cefazolin >30 10-30 <10 (q8h) (q12h) (q24h) Cefotaxime >50 10-50 <10 (q6-8h) (q12h) (q24h) Ceftriaxone NO CHANGE NECESSARY NO Cefoxitin >50 30-50 10-29 <10 (q6-8h) (q8h) (q12h) (q24h) Ceftazidime >50 30-50 10-29 <10 (q8h) (q12h) (q24h) (q48h), PD Cefuroxime >30 10-30 <10 (q8h) (q12h) (q24h) Miscellaneous Acyclovir >50 30-50 10-29 <10 (q8h) (q12h) (q24h) (50% q24h) Aminoglycosides c Drug Handbook for Refer to Pediatric Dosage (Lexicomp) more information, PD Azithromycin NO CHANGE NECESSARY NO Clindamycin NO CHANGE NECESSARY NO Fluconazole >50 10-50 <10 (q24h) (50% q24h) (50% q48h) Ganciclovir >50 30-50 10-29 <10 (induction doses) 5 mg/kg q12h 2.5 mg/kg q24h 1.25 mg/kg q24h 1.25 mg/kg 3x/wk Meropenem >50 30-50 10-29 <10 (q8h) (q12h) (50% q12h) (50% q24h) Metronidazole >10 <10 (q8h) (50% q8h) TMP/SMX a >50 30-50 10-29 <10 (q6-8h) (q8h) (q12h) (q24h) generally not recommended a Vancomycin c >50 30-50 10-29 <10 (q6-8h) (q12h) (q24h) dose as needed per serum concentration a. b. c., PD Suggested doses for individualized dosage modifications or more information contact the Department of Pharmaceutical Services. To estimate creatinine clearance (CL CR) (ml/min/1.73 m 2 ) use the following calculation: CL CR = K x height (cm) x 88.4 S CR (μmoles/l) where K = age-specific constant: <1 year preterm: 0.33 < 1 year full term: 0.45 1-12 years: 0.55 > 12 years female: 0.55 > 12 years male: 0.7 Monitor serum concentrations, for individualized dosage modifications contact Department of Pharmaceutical Services. NO 10