University of Manitoba, Health Sciences Centre, and...
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49th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, September 12-15, 2009 Antimicrobial Resistance in 13,163 Pathogens from Canadian Hospitals: CANWARD Study 2007 and 2008 University of Manitoba, Health Sciences Centre, and National Microbiology Laboratory, Winnipeg, Manitoba, Canada Dr. George G. Zhanel MS673-820 Sherbrook Street Winnipeg, Manitoba, Canada R3A 1R9 Phone: (204) - 787 - 4902 Fax: (204) - 787 - 4699 Email: [email protected] ABSTRACT (REVISED) ABSTRACT (REVISED) INTRODUCTION Infections caused by antibiotic resistant pathogens is a Canadian and global crisis. Antibiotic resistant pathogens including methicillin-resistant Staphylococcus aureus (MRSA, community associated and hospital associated), vancomycin-resistant Enterococcus species (VRE), penicillin-resistant Streptococcus pneumoniae (PRSP), extended spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella species and fluoroquinolone-resistant and carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa are increasing in prevalence in Canada and around the world. Available therapeutic options for the treatment of these antibiotic resistant organisms are severely limited as these organisms frequently display a multidrug resistant (MDR) phenotype. The goal of the CANWARD study was to assess pathogens associated with and antimicrobial resistance patterns in respiratory, bacteremic, urinary, and wound/IV site infections in Canadian hospitalized patients on medical/surgical wards (W), emergency rooms (ER), outpatient clinics (C) and intensive care units (ICU). Objectives of CANWARD: 1. To determine the pathogens associated with respiratory, urinary, bacteremic and wound/IV site infections in Canadian patients affiliated with hospitals. 2. To determine the prevalence of antimicrobial resistance in pathogens associated with respiratory, urinary, bacteremic and wound/IV site infections in Canadian patients affiliated with hospitals. 3. To assess the activity of antimicrobials against respiratory, urinary, bacteremic and wound/IV site pathogens in Canadian patients affiliated with hospitals. Background: The CANWARD study assessed the pathogens causing infections in Canadian hospitals as well as their antimicrobial resistance patterns. Methods: In a prospective, national surveillance study Jan to Dec 2007 and 2008, inclusive, 12 hospitals (10 in 2008) across Canada submitted clinical isolates from patients attending hospital clinics (C), emergency rooms (ER), medical/surgical wards (W) and intensive care units (ICU). Susceptibility testing was performed by CLSI methods. Results: 13,163 isolates, 44.3%, 29.8%, 17.5%, and 8.4% from blood, respiratory, urine and wound specimens, respectively were collected. Patient demographics were 53.7%/46.3% male/female, 12.8% ≤ 17yrs, 46.3% 18-64 yrs and 40.9% ≥ 65yrs. Isolates were obtained from patients on W 38.7%, ER 27.9%, C 17.1% and ICU 16.2%. Most common pathogens were: E. coli 21.6%, S. aureus (MSSA) 13.9%, S. pneumoniae (SPN) 9.5%, P. aeruginosa 7.7%, K. pneumoniae 7.2%, MRSA 5.0%, H. influenzae 4.2% and Enterococcus spp. 3.1%. Resistance rates (RR) for E. coli were: 0% ertapenem (ERT), 0% tigecycline (TGC), 0.2% amikacin (AMK), 1.3% piperacillin/tazobactam (P/T), 7.1% ceftriaxone (CTR), ciprofloxacin (CIP) 23.5% and 27.0% with cotrimoxazole (T/S). RR for P. aeruginosa were: 1.2% colistin, 6.1% AMK, 7.2% MER, 7.6% P/T, 10.0% cefepime, and 21.8% CIP. RR for MRSA were: 0% ceftobiprole (BPR), daptomycin (DAP), linezolid (LZD), and TGC, 11.4% T/S, 59.2% clindamycin, 88.6% CIP and 89.0% for clarithromycin. Conclusions: E. coli , MSSA, SPN, P. aeruginosa , K. pneumoniae , Enterococcus spp. and MRSA are the most common pathogens in Canadian hospitals. RR for E. coli were lowest with ERT, TGC, AMK and P/T. RR for P. aeruginosa were lowest with colistin, AMK, MER and P/T. No resistance occurred in MRSA to BPR, DAP, LZD, and TGC. MATERIALS AND METHODS Participating Sites: From January 2007 to December 2008, 12 sentinel hospital sites (10 in 2008) in major population centres in 7 of the 10 provinces in Canada were recruited. These sites were geographically distributed in a population based fashion: (BC [1 site], Alberta [1 site], Saskatchewan [1 site], Manitoba [1 site], Ontario [4 sites], Quebec [3 sites], Maritimes [1 site]). Isolate Collection: Each study site was asked to collect and submit pathogens (one per patient) as detailed below: Respiratory Tract Infections: 150 consecutive isolates per site from patients hospitalized with respiratory tract infections (community or nosocomial). Specimen sources included sputums, tracheal secretions, BAL, bronchoscopy washes/protective brush specimens. Skin/Skin Structure Infections (wounds): 50 consecutive isolates per site from patients with wound/IV site infections. Specimen sources included high quality swabs, biopsies and aspirates. Urinary Tract Infections: 100 consecutive isolates per site from patients (inpatients or outpatients) with urinary tract infections. Blood Stream Infections: 20 consecutive blood stream infection isolates/site/month (240 per year). All isolates were deemed clinically significant by that site. All organisms were identified at each site using local site criteria and at the reference site, where indicated. At study sites, isolates were subcultured on appropriate solid media and incubated overnight. Amies semi-solid transport media containing charcoal (Difco Laboratories, Detroit, MI) were inoculated with the isolate and sent to the coordinating laboratory (Health Sciences Centre, Winnipeg, Manitoba, Canada), where isolates were subcultured on appropriate media and stocked in skim milk at –70°C. Antimicrobial Susceptibility Testing: A custom designed microtitre panel was designed with a variety of antimicrobials. Antimicrobials were obtained as laboratory grade powders from their respective manufacturers. Stock solutions were prepared and dilutions made as described by the Clinical Laboratory Standards Institute (2006 CLSI). Following two subcultures from frozen stock, the MICs of the antimicrobial agents for the isolates were determined by the CLSI approved broth microdilution method. Briefly, 96-well custom designed microtitre plates containing doubling antibiotic dilutions in 100 μl/well of cation adjusted Mueller-Hinton broth (eg. for Enterobacteriaceae) with or without lysed horse blood (2-5% V/V) [eg. for S. pneumoniae ) was inoculated to achieve a final concentration of approximately 5 x 10 5 CFU/mL and incubated in ambient air for 24 hours prior to reading. Colony counts were performed periodically to confirm inocula. Quality control was performed every two weeks using a variety of ATCC QC organisms. For all antimicrobials tested, MIC interpretive standards were defined according to CLSI breakpoints (M100-S16, 2006). The following interpretive breakpoints (FDA) were used for tigecycline: susceptible (S), intermediate (I) and resistant (R) ( µ g/mL): S. aureus (MSSA and MRSA) ≤ 0.5 (S); Enterococcus spp., ≤ 0.25 (S); Enterobacteriaceae, ≤ 2 (S), 4 (I), and ≥ 8 (R). Health Canada breakpoints were used for ceftobiprole: susceptible (S), intermediate (I) and resistant (R) (µg/mL): S. aureus (MSSA and MRSA) 4 (S); Streptococcus spp. other than S. pneumoniae ≤ 0.5 (S); Enterobacteriaceae, ≤ 1 (S), 2 (I), and ≥ 4 (R). ACKNOWLEDGEMENTS The authors would like to thank the participating centres of CANWARD, investigators and laboratory site staff for their support (see Results). The CANWARD study was supported in part by Abbott, Affinium, Astellas, Bayer, Janssen Ortho/Ortho McNeil, Merck, Pfizer, Sepracor, TaiGen, Targanta and Wyeth. CONCLUSIONS RESULTS C2-1953 C2-1953 G. G. ZHANEL*, M. DeCORBY, K. NICHOL, N. LAING, B. WESHNOWESKI, R. VASHISHT, F. TAILOR, A. WIERZBOWSKI, P. BAUDRY, P. LAGACE-WIENS, A. WALKTY, H. ADAM, J. A. KARLOWSKY, M. McCRACKEN, M. R. MULVEY, CANADIAN ANTIMICROBIAL RESISTANCE ALLIANCE (CARA), and D.J. HOBAN Demographics of CANWARD 2007-2008 Most Common Pathogens Overall (n=13,163) Most Common Pathogens by Infectious Site Activity of various antimicrobials against select pathogens from the CANWARD Study Participating CANWARD Investigators / Sites • Isolates were obtained from patients on W 38.7% (29.6% medical/9.1% surgical), ER 27.9%, C 17.1% and ICU 16.2%. • The most common pathogens were: E. coli 21.6%, S. aureus (MSSA) 13.9%, S. pneu- moniae 9.5%, P. aeruginosa 7.7%, K. pneumoniae 7.2%, MRSA 5.0%, H. influenzae 4.2% and Enterococcus spp. 3.1%. • Susceptibility rates for E. coli were: 100% ertapenem and meropenem (MER), 99.8% tigecy- cline (TGC), 99.5% amikacin (AMK) and 97.3% piperacillin/tazobactam (P/T) and 95.0% cefto- biprole, 91.4% ceftriaxone (CTR), 89.3% gentamicin (GEN), 73.0% trimethoprim/sulfamethoxazole (T/S) and 76.2% ciprofloxacin (CIP). • Susceptibility rates for P. aeruginosa were: 92.5% P/T, 88.8% MER, 88.2% ceftazidime, 88.6% AMK, 64.2% GEN and 69.5 % CIP. • Susceptibility rates for MRSA were: 100% ceftobiprole, DAP, LZD and TGC, 99.8% vancomy- cin, 88.6% T/S, 40.6% clindamycin, 11.3% CIP and 10.8% for clarithromycin. Gender n % of Total Female 6014 45.7 Male 7149 54.3 13,163 Age Group n % of Total 17 and under 1686 12.8 18 to 64 6096 46.3 65 or greater 5381 40.9 13,163 Specimen Source n % of Total Blood 5825 44.3 Respiratory 3918 29.8 Urine 2310 17.5 Wound / IV Site 1110 8.4 13,163 Ward Type n % of Total Clinic 2249 17.1 ER 3676 27.9 ICU 2137 16.2 Medical 3900 29.6 Surgical 1201 9.1 13,163 Rank Organism n % of Total 1 E. coli 2837 21.6 2 S. aureus - MSSA 1830 13.9 3 S. pneumoniae 1246 9.5 4 P. aeruginosa 1007 7.7 5 K. pneumoniae 945 7.2 6 S. aureus – MRSA 657 5.0 7 CNS/ S. epidermidis 600 4.6 8 H. influenzae 556 4.2 9 Enterococcus spp. 413 3.1 10 E. cloacae 280 2.1 11 E. faecalis 262 2.0 12 P. mirabilis 204 1.5 13 S. pyogenes 202 1.5 14 S. agalactiae 189 1.4 15 S. marcescens 177 1.3 16 K. oxytoca 176 1.3 17 S. maltophilia 164 1.2 18 M. catarrhalis 145 1.1 19 S. viridans 110 0.8 20 E. faecium 108 0.8 Other 1055 8.0 13,163 Rank Organism n % of Total 1 E. coli 1316 22.7 2 S. aureus - MSSA 786 13.5 3 CNS / S. epidermidis 517 8.9 4 K. pneumoniae 404 7.0 5 S. pneumoniae 355 6.1 6 S. aureus - MRSA 278 4.8 7 E. faecalis 243 4.2 8 P. aeruginosa 228 3.9 9 E. cloacae 136 2.3 10 C. albicans 118 2.0 11 S. pyogenes 111 1.9 12 S. viridans 108 1.9 13 S. agalactiae 103 1.8 14 E. faecium 100 1.7 15 K. oxytoca 83 1.4 16 S. marcescens 75 1.3 17 P. mirabilis 67 1.2 18 C. glabrata 39 0.7 19 S. mitis 36 0.6 20 BHS gr G 32 0.6 Other 690 11.9 5825 Rank Organism n % of Total 1 S. pneumoniae 895 22.9 2 S. aureus - MSSA 619 15.8 3 P. aeruginosa 597 15.2 4 H. influenzae 523 13.4 5 S. aureus - MRSA 215 5.5 6 E. coli 162 4.1 7 M. catarrhalis 143 3.7 8 K. pneumoniae 127 3.2 9 S. maltophilia 121 3.1 10 S. marcescens 83 2.1 11 E. cloacae 68 1.7 12 K. oxytoca 47 1.2 13 P. mirabilis 29 0.7 14 H. parainfluenzae 28 0.7 15 S. agalactiae 25 0.6 16 S. pyogenes 21 0.5 17 Enterococcus spp. 19 0.5 18 E. aerogenes 18 0.5 19 Haemophilus spp. 14 0.4 20 C. freundii 11 0.3 Other 153 3.9 3918 Rank Organism n % of Total 1 E. coli 1259 54.5 2 Enterococcus spp. 318 13.8 3 K. pneumoniae 210 9.1 4 P. mirabilis 95 4.1 5 P. aeruginosa 78 3.4 6 CNS / S. epidermidis 46 2.0 7 E. cloacae 41 1.8 8 S. aureus - MSSA 36 1.6 9 K. oxytoca 36 1.6 10 S. agalactiae 33 1.4 11 S. aureus - MRSA 30 1.3 12 C. freundii 24 1.0 13 M. morganii 18 0.8 14 C. koseri 11 0.5 15 S. marcescens 9 0.4 16 E. aerogenes 8 0.3 17 Klebsiella spp. 8 0.3 18 S. saprophyticus 7 0.3 19 P. vulgaris 4 0.2 20 S. maltophilia 3 0.1 Other 36 1.6 2310 Rank Organism n % of Total 1 S. aureus - MSSA 387 34.9 2 S. aureus - MRSA 134 12.1 3 P. aeruginosa 103 9.3 4 E. coli 97 8.7 5 S. pyogenes 69 6.2 6 Enterococcus spp. 47 4.2 7 CNS / S. epidermidis 36 3.2 8 E. cloacae 35 3.2 9 K. pneumoniae 31 2.8 10 S. agalactiae 28 2.5 11 P. mirabilis 13 1.2 12 K. oxytoca 10 0.9 13 S. marcescens 10 0.9 14 S. maltophilia 10 0.9 15 E. faecalis 9 0.8 16 C. freundii 8 0.7 17 BHS gr G 8 0.7 18 E. faecium 7 0.6 19 M. morganii 6 0.5 20 H. influenzae 6 0.5 Other 56 5.0 1110 Hospital Clinic Rank Organism n % of Total 1 E. coli 445 19.8 2 S. aureus - MSSA 392 17.4 3 P. aeruginosa 270 12.0 4 S. pneumoniae 215 9.6 5 H. influenzae 152 6.8 6 CNS / S. epidermidis 99 4.4 7 K. pneumoniae 77 3.4 8 S. aureus - MRSA 71 3.2 9 Enterococcus spp. 64 2.8 10 S. maltophilia 49 2.2 11 M. catarrhalis 48 2.1 12 E. cloacae 36 1.6 13 S. marcescens 30 1.3 14 S. agalactiae 27 1.2 15 P. mirabilis 26 1.2 16 E. faecalis 25 1.1 17 S. pyogenes 23 1.0 18 K. oxytoca 23 1.0 19 C. freundii 14 0.6 20 H. parainfluenzae 11 0.5 Other 152 6.8 2249 Emergency Room Rank Organism n % of Total 1 E. coli 1101 30.0 2 S. aureus - MSSA 512 13.9 3 S. pneumoniae 400 10.9 4 K. pneumoniae 206 5.6 5 P. aeruginosa 155 4.2 6 S. aureus - MRSA 154 4.2 7 H. influenzae 144 3.9 8 S. pyogenes 120 3.3 9 CNS / S. epidermidis 107 2.9 10 S. agalactiae 76 2.1 11 Enterococcus spp. 69 1.9 12 P. mirabilis 67 1.8 13 E. faecalis 60 1.6 14 E. cloacae 43 1.2 15 K. oxytoca 43 1.2 16 S. viridans 42 1.1 17 BHS gr G 27 0.7 18 M. catarrhalis 25 0.7 19 M. morganii 21 0.6 20 S. marcescens 20 0.5 Other 284 7.7 3676 ICU Rank Organism n % of Total 1 S. aureus - MSSA 288 13.5 2 S. pneumoniae 249 11.7 3 E. coli 235 11.0 4 P. aeruginosa 171 8.0 5 CNS / S. epidermidis 150 7.0 6 K. pneumoniae 143 6.7 7 S. aureus - MRSA 122 5.7 8 H. influenzae 97 4.5 9 E. cloacae 82 3.8 10 Enterococcus spp. 49 2.3 11 S. marcescens 48 2.2 12 E. faecalis 47 2.2 13 S. maltophilia 44 2.1 14 K. oxytoca 43 2.0 15 C. albicans 40 1.9 16 M. catarrhalis 32 1.5 17 E. faecium 24 1.1 18 S. agalactiae 21 1.0 19 P. mirabilis 20 0.9 20 E. aerogenes 18 0.8 Other 214 10.0 2137 Medical Ward Rank Organism n % of Total 1 E. coli 852 21.9 2 S. aureus - MSSA 465 12.0 3 P. aeruginosa 325 8.4 4 S. pneumoniae 316 8.1 5 K. pneumoniae 263 6.8 6 S. aureus - MRSA 222 5.7 7 CNS / S. epidermidis 201 5.2 8 Enterococcus spp. 165 4.2 9 H. influenzae 124 3.2 10 E. faecalis 94 2.4 11 E. cloacae 79 2.0 12 S. marcescens 66 1.7 13 P. mirabilis 62 1.6 14 S. agalactiae 57 1.5 15 C. albicans 53 1.4 16 K. oxytoca 51 1.3 17 S. maltophilia 43 1.1 18 E. faecium 42 1.1 19 S. viridans 42 1.1 20 S. pyogenes 30 0.8 Other 348 9.0 3900 Surgical Ward Rank Organism n % of Total 1 E. coli 201 16.8 2 S. aureus - MSSA 171 14.3 3 S. aureus - MRSA 88 7.3 4 P. aeruginosa 85 7.1 5 K. pneumoniae 83 6.9 6 S. pneumoniae 70 5.8 7 Enterococcus spp. 64 5.3 8 CNS / S. epidermidis 48 4.0 9 H. influenzae 41 3.4 10 E. cloacae 40 3.3 11 E. faecalis 31 2.6 12 P. mirabilis 29 2.4 13 E. faecium 22 1.8 14 C. albicans 18 1.5 15 K. oxytoca 16 1.3 16 S. pyogenes 16 1.3 17 S. marcescens 13 1.1 18 S. maltophilia 12 1.0 19 M. catarrhalis 12 1.0 20 C. glabrata 12 1.0 Other 129 10.8 1201 Dr. D. Roscoe Vancouver Hospital Vancouver BC Dr. S. Poutanen Mount Sinai Hospital Toronto ON Dr. R. Rennie University of Alberta Hospitals Edmonton AB Dr. F. Chan Children's Hosp. of Eastern Ontario Ottawa ON Dr. J. Blondeau Royal University Hospital Saskatoon SK Dr. M. Laverdiere Hopital Maisonneuve-Rosemont Montreal QC Drs. Hoban / Zhanel Health Sciences Centre Winnipeg MB Dr. V. Loo Montreal General Hospital Montreal QC Dr. Z. Hussain London Health Sciences Centre London ON Dr. V. Loo Royal Victoria Hospital (2007 only) Montreal QC Dr. C. Lee St. Joseph's Hospital (2007 only) Hamilton ON Dr. R. Davidson Queen Elizabeth II HSC Halifax NS Most Common Pathogens by Ward Type % Sus % Int % Res MIC 50 MIC 90 Minimum Maximum Amikacin 99.5% 0.3% 0.2% ≤ 2 4 ≤ 2 > 64 Amoxicillin Clavulanate 95.4% 3.9% 0.8% 4 8 0.5 > 32 Cefazolin 84.4% 3.1% 12.5% 2 64 0.5 > 128 Cefepime 96.0% 2.2% 1.8% ≤ 1 ≤ 1 ≤ 1 > 32 Cefoxitin 91.3% 3.7% 5.0% 4 8 ≤ 0.06 > 32 Ceftazidime 95.9% 0.6% 3.5% ≤ 0.5 1 ≤ 0.5 > 32 Ceftobiprole* 95.0% 0.4% 7.6% ≤ 1 ≤ 1 ≤ 1 > 32 Ceftriaxone 91.4% 1.5% 7.1% ≤ 1 2 ≤ 1 > 64 Ciprofloxacin 76.2% 0.3% 23.5% ≤ 0.06 > 16 ≤ 0.06 > 16 Colistin No breakpoints defined 0.5 1 ≤ 0.06 > 16 Ertapenem 100.0% ≤ 0.06 ≤ 0.06 ≤ 0.06 1 Gentamicin 89.3% 0.4% 10.3% ≤ 0.5 16 ≤ 0.5 > 32 Levofloxacin 76.5% 0.7% 22.8% ≤ 0.06 16 ≤ 0.06 > 32 Meropenem 100.0% ≤ 0.06 ≤ 0.06 ≤ 0.06 0.12 Moxifloxacin No breakpoints defined ≤ 0.06 > 16 ≤ 0.06 > 16 Nitrofurantoin 96.5% 2.4% 1.1% 16 32 0.25 > 256 Piperacillin Tazobactam 97.3% 1.4% 1.3% 2 4 ≤ 1 256 Tigecycline* 99.8% 0.2% 0.5 1 0.12 4 Trimethoprim Sulfa 73.0% 27.0% ≤ 0.12 > 8 ≤ 0.12 > 8 Susceptibility Range *Interpretive breakpoints defined by Health Canada (ceftobiprole) or FDA (tigecycline) where applicable E.coli (2833) % Sus % Int % Res MIC 50 MIC 90 Minimum Maximum Amikacin 88.6% 5.4% 6.1% 8 32 ≤ 2 > 64 Cefepime 72.4% 17.6% 10.0% 4 32 ≤ 1 > 32 Ceftazidime 88.2% 2.7% 9.1% 2 16 ≤ 0.5 > 32 Ceftobiprole No breakpoints defined 4 16 0.25 > 32 Ciprofloxacin 69.5% 8.8% 21.8% 0.5 8 ≤ 0.06 > 16 Colistin 90.8% 8.0% 1.2% 2 2 0.5 > 16 Gentamicin 64.2% 18.1% 17.7% 4 16 ≤ 0.5 > 32 Levofloxacin 62.6% 12.6% 24.8% 1 16 ≤ 0.06 > 32 Meropenem 88.8% 4.1% 7.2% 0.5 8 ≤ 0.06 > 32 Piperacillin Tazobactam 92.5% 7.5% 4 64 ≤ 1 > 512 Susceptibility Range P. aeruginosa (1006) % Sus % Int % Res MIC 50 MIC 90 Minimum Maximum Cefazolin 100.0%** 128 > 128 2 > 128 Cefepime 100.0%** > 32 > 32 4 > 32 Cefoxitin 100.0%** > 32 > 32 1 > 32 Ceftazidime 100.0%** > 32 > 32 16 > 32 Ceftobiprole* 100.0% 1 2 0.5 4 Ceftriaxone 100.0%** > 64 > 64 16 > 64 Ciprofloxacin 11.3% 0.2% 88.6% > 16 > 16 0.25 > 16 Clarithromycin 10.8% 0.2% 89.0% > 32 > 32 ≤ 0.03 > 32 Clindamycin 40.6% 0.2% 59.2% > 8 > 8 ≤ 0.12 > 8 Daptomycin 100.0% 0.12 0.25 0.06 1 Ertapenem 100.0%** 8 > 32 0.5 > 32 Levofloxacin 12.0% 88.0% > 32 > 32 0.12 > 32 Linezolid 100.0% 2 2 ≤ 0.12 4 Meropenem 100.0%** 8 32 0.12 > 32 Moxifloxacin 12.0% 0.3% 87.7% 8 > 16 ≤ 0.06 > 16 Nitrofurantoin 100.0% 16 16 8 32 Piperacillin Tazobactam 100.0%** 64 128 ≤ 1 512 Tigecycline* 100.0% 0.25 0.25 0.12 0.25 Trimethoprim Sulfa 88.6% 11.4% ≤ 0.12 8 ≤ 0.12 > 8 Vancomycin 99.8% 0.2% 1 1 ≤ 0.5 4 *Interpretive breakpoints defined by Health Canada (ceftobiprole) or FDA (tigecycline) where applicable **Based on oxacillin susceptibility Susceptibility Range S. aureus - MRSA (657) Wound / IV Site Urine Blood Respiratory
Transcript of University of Manitoba, Health Sciences Centre, and...
49th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, September 12-15, 2009
Antimicrobial Resistance in 13,163 Pathogens from Canadian Hospitals: CANWARD Study 2007 and 2008
University of Manitoba, Health Sciences Centre, and National Microbiology Laboratory, Winnipeg, Manitoba, Canada
Dr. George G. ZhanelMS673-820 Sherbrook StreetWinnipeg, Manitoba, CanadaR3A 1R9Phone: (204) - 787 - 4902Fax: (204) - 787 - 4699Email: [email protected]
ABSTRACT (REVISED)ABSTRACT (REVISED)
INTRODUCTION
Infections caused by antibiotic resistant pathogens is a Canadian and global crisis. Antibiotic resistant pathogens including methicillin-resistant Staphylococcus aureus (MRSA, community associated and hospital associated), vancomycin-resistant Enterococcus species (VRE), penicillin-resistant Streptococcus pneumoniae (PRSP), extended spectrum β-lactamase (ESBL) producing Escherichia coli and Klebsiella species and fluoroquinolone-resistant and carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa are increasing in prevalence in Canada and around the world. Available therapeutic options for the treatment of these antibiotic resistant organisms are severely limited as these organisms frequently display a multidrug resistant (MDR) phenotype. The goal of the CANWARD study was to assess pathogens associated with and antimicrobial resistance patterns in respiratory, bacteremic, urinary, and wound/IV site infections in Canadian hospitalized patients on medical/surgical wards (W), emergency rooms (ER), outpatient clinics (C) and intensive care units (ICU).
Objectives of CANWARD:1. To determine the pathogens associated with respiratory, urinary, bacteremic and wound/IV site infections in Canadian patients affiliated with hospitals. 2. To determine the prevalence of antimicrobial resistance in pathogens associated with respiratory, urinary, bacteremic and wound/IV site infections in Canadian patients affiliated with hospitals. 3. To assess the activity of antimicrobials against respiratory, urinary, bacteremic and wound/IV site pathogens in Canadian patients affiliated with hospitals.
Background: The CANWARD study assessed the pathogens causing infections in Canadian hospitals as well as their antimicrobial resistance patterns. Methods: In a prospective, national surveillance study Jan to Dec 2007 and 2008, inclusive, 12 hospitals (10 in 2008) across Canada submitted clinical isolates from patients attending hospital clinics (C), emergency rooms (ER), medical/surgical wards (W) and intensive care units (ICU). Susceptibility testing was performed by CLSI methods.
Results: 13,163 isolates, 44.3%, 29.8%, 17.5%, and 8.4% from blood, respiratory, urine and wound specimens, respectively were collected. Patient demographics were 53.7%/46.3% male/female, 12.8% ≤ 17yrs, 46.3% 18-64 yrs and 40.9% ≥ 65yrs. Isolates were obtained from patients on W 38.7%, ER 27.9%, C 17.1% and ICU 16.2%. Most common pathogens were: E. coli 21.6%, S. aureus (MSSA) 13.9%, S. pneumoniae (SPN) 9.5%, P. aeruginosa 7.7%, K. pneumoniae 7.2%, MRSA 5.0%, H. influenzae 4.2% and Enterococcus spp. 3.1%. Resistance rates (RR) for E. coli were: 0% ertapenem (ERT), 0% tigecycline (TGC), 0.2% amikacin (AMK), 1.3% piperacillin/tazobactam (P/T), 7.1% ceftriaxone (CTR), ciprofloxacin (CIP) 23.5% and 27.0% with cotrimoxazole (T/S). RR for P. aeruginosa were: 1.2% colistin, 6.1% AMK, 7.2% MER, 7.6% P/T, 10.0% cefepime, and 21.8% CIP. RR for MRSA were: 0% ceftobiprole (BPR), daptomycin (DAP), l inezolid (LZD), and TGC, 11.4% T/S, 59.2% clindamycin, 88.6% CIP and 89.0% for clarithromycin. Conclusions: E. coli, MSSA, SPN, P. aeruginosa, K. pneumoniae, Enterococcus spp. and MRSA are the most common pathogens in Canadian hospitals. RR for E. coli were lowest with ERT, TGC, AMK and P/T. RR for P. aeruginosa were lowest with colistin, AMK, MER and P/T. No resistance occurred in MRSA to BPR, DAP, LZD, and TGC.
MATERIALS AND METHODSParticipating Sites: From January 2007 to December 2008, 12 sentinel hospital sites (10 in 2008) in major population centres in 7 of the 10 provinces in Canada were recruited. These sites were geographically distributed in a population based fashion: (BC [1 site], Alberta [1 site], Saskatchewan [1 site], Manitoba [1 site], Ontario [4 sites], Quebec [3 sites], Maritimes [1 site]). Isolate Collection: Each study site was asked to collect and submit pathogens (one per patient) as detailed below: Respiratory Tract Infections: 150 consecutive isolates per site from patients hospitalized with respiratory tract infections (community or nosocomial). Specimen sources included sputums, tracheal secretions, BAL, bronchoscopy washes/protective brush specimens. Skin/Skin Structure Infections (wounds): 50 consecutive isolates per site from patients with wound/IV site infections. Specimen sources included high quality swabs, biopsies and aspirates. Urinary Tract Infections: 100 consecutive isolates per site from patients (inpatients or outpatients) with urinary tract infections. Blood Stream Infections: 20 consecutive blood stream infection isolates/site/month (240 per year). All isolates were deemed clinically significant by that site. All organisms were identified at each site using local site criteria and at the reference site, where indicated. At study sites, isolates were subcultured on appropriate solid media and incubated overnight. Amies semi-solid transport media containing charcoal (Difco Laboratories, Detroit, MI) were inoculated with the isolate and sent to the coordinating laboratory (Health Sciences Centre, Winnipeg, Manitoba, Canada), where isolates were subcultured on appropriate media and stocked in skim milk at –70°C. Antimicrobial Susceptibility Testing: A custom designed microtitre panel was designed with a variety of antimicrobials. Antimicrobials were obtained as laboratory grade powders from their respective manufacturers. Stock solutions were prepared and dilutions made as described by the Clinical Laboratory Standards Institute (2006 CLSI). Following two subcultures from frozen stock, the MICs of the antimicrobial agents for the isolates were determined by the CLSI approved broth microdilution method. Briefly, 96-well custom designed microtitre plates containing doubling antibiotic dilutions in 100 μl/well of cation adjusted Mueller-Hinton broth (eg. for Enterobacteriaceae) with or without lysed horse blood (2-5% V/V) [eg. for S. pneumoniae) was inoculated to achieve a final concentration of approximately 5 x 105 CFU/mL and incubated in ambient air for 24 hours prior to reading. Colony counts were performed periodically to confirm inocula. Quality control was performed every two weeks using a variety of ATCC QC organisms. For all antimicrobials tested, MIC interpretive standards were defined according to CLSI breakpoints (M100-S16, 2006). The fol lowing interpretive breakpoints (FDA) were used for t igecycline: susceptible (S), in termediate ( I ) and resistant (R) (µg/mL): S. aureus (MSSA and MRSA) ≤ 0 .5 (S); Enterococcus spp., ≤ 0.25 (S); Enterobacteriaceae, ≤ 2 (S), 4 (I), and ≥ 8 (R). Health Canada breakpoints were used for ceftobiprole: susceptible (S), intermediate (I) and resistant (R) (µg/mL): S. aureus (MSSA and MRSA) 4 (S); Streptococcus spp. other than S. pneumoniae ≤ 0.5 (S); Enterobacteriaceae, ≤ 1 (S), 2 (I), and ≥ 4 (R).
ACKNOWLEDGEMENTSThe authors would like to thank the participating centres of CANWARD, investigators and laboratory site staff for their support (see Results). The CANWARD study was supported in part by Abbott, Affinium, Astellas, Bayer, Janssen Ortho/Ortho McNeil, Merck, Pfizer, Sepracor, TaiGen, Targanta and Wyeth.
CONCLUSIONS
RESULTS
C2-1953C2-1953
G. G. ZHANEL*, M. DeCORBY, K. NICHOL, N. LAING, B. WESHNOWESKI, R. VASHISHT, F. TAILOR, A. WIERZBOWSKI, P. BAUDRY, P. LAGACE-WIENS, A. WALKTY, H. ADAM, J. A. KARLOWSKY, M. McCRACKEN, M. R. MULVEY, CANADIAN ANTIMICROBIAL RESISTANCE ALLIANCE (CARA), and D.J. HOBAN
Demographics of CANWARD 2007-2008 Most Common Pathogens Overall (n=13,163) Most Common Pathogens by Infectious Site
Activity of various antimicrobials against select pathogens from the CANWARD Study
Participating CANWARD Investigators / Sites
• Isolates were obtained from patients on W 38.7% (29.6% medical/9.1% surgical), ER 27.9%, C 17.1% and ICU 16.2%.• The most common pathogens were: E. coli 21.6%, S. aureus (MSSA) 13.9%, S. pneu-moniae 9.5%, P. aeruginosa 7.7%, K. pneumoniae 7.2%, MRSA 5.0%, H. influenzae 4.2% and Enterococcus spp. 3.1%.• Susceptibility rates for E. coli were: 100% ertapenem and meropenem (MER), 99.8% tigecy-cline (TGC), 99.5% amikacin (AMK) and 97.3% piperacillin/tazobactam (P/T) and 95.0% cefto-biprole, 91.4% ceftriaxone (CTR), 89.3% gentamicin (GEN), 73.0% trimethoprim/sulfamethoxazole (T/S) and 76.2% ciprofloxacin (CIP). • Susceptibility rates for P. aeruginosa were: 92.5% P/T, 88.8% MER, 88.2% ceftazidime, 88.6% AMK, 64.2% GEN and 69.5 % CIP. • Susceptibility rates for MRSA were: 100% ceftobiprole, DAP, LZD and TGC, 99.8% vancomy-cin, 88.6% T/S, 40.6% clindamycin, 11.3% CIP and 10.8% for clarithromycin.
Gender n % of Total
Female 6014 45.7Male 7149 54.3
13,163
Age Group n % of Total
17 and under 1686 12.818 to 64 6096 46.365 or greater 5381 40.9
13,163
Specimen Source n % of Total
Blood 5825 44.3Respiratory 3918 29.8Urine 2310 17.5Wound / IV Site 1110 8.4
13,163
Ward Type n % of Total
Clinic 2249 17.1ER 3676 27.9ICU 2137 16.2Medical 3900 29.6Surgical 1201 9.1
13,163
Rank Organism n % of Total
1 E. coli 2837 21.62 S. aureus - MSSA 1830 13.93 S. pneumoniae 1246 9.54 P. aeruginosa 1007 7.75 K. pneumoniae 945 7.26 S. aureus – MRSA 657 5.07 CNS/ S. epidermidis 600 4.68 H. influenzae 556 4.29 Enterococcus spp. 413 3.110 E. cloacae 280 2.111 E. faecalis 262 2.012 P. mirabilis 204 1.513 S. pyogenes 202 1.514 S. agalactiae 189 1.415 S. marcescens 177 1.316 K. oxytoca 176 1.317 S. maltophilia 164 1.218 M. catarrhalis 145 1.119 S. viridans 110 0.820 E. faecium 108 0.8
Other 1055 8.013,163
Rank Organism n % of Total1 E. coli 1316 22.72 S. aureus - MSSA 786 13.53 CNS / S. epidermidis 517 8.94 K. pneumoniae 404 7.05 S. pneumoniae 355 6.16 S. aureus - MRSA 278 4.87 E. faecalis 243 4.28 P. aeruginosa 228 3.99 E. cloacae 136 2.310 C. albicans 118 2.011 S. pyogenes 111 1.912 S. viridans 108 1.913 S. agalactiae 103 1.814 E. faecium 100 1.715 K. oxytoca 83 1.416 S. marcescens 75 1.317 P. mirabilis 67 1.218 C. glabrata 39 0.719 S. mitis 36 0.620 BHS gr G 32 0.6
Other 690 11.95825
Rank Organism n % of Total1 S. pneumoniae 895 22.92 S. aureus - MSSA 619 15.83 P. aeruginosa 597 15.24 H. influenzae 523 13.45 S. aureus - MRSA 215 5.56 E. coli 162 4.17 M. catarrhalis 143 3.78 K. pneumoniae 127 3.29 S. maltophilia 121 3.110 S. marcescens 83 2.111 E. cloacae 68 1.712 K. oxytoca 47 1.213 P. mirabilis 29 0.714 H. parainfluenzae 28 0.715 S. agalactiae 25 0.616 S. pyogenes 21 0.517 Enterococcus spp. 19 0.518 E. aerogenes 18 0.519 Haemophilus spp. 14 0.420 C. freundii 11 0.3
Other 153 3.93918
Rank Organism n % of Total1 E. coli 1259 54.52 Enterococcus spp. 318 13.83 K. pneumoniae 210 9.14 P. mirabilis 95 4.15 P. aeruginosa 78 3.46 CNS / S. epidermidis 46 2.07 E. cloacae 41 1.88 S. aureus - MSSA 36 1.69 K. oxytoca 36 1.610 S. agalactiae 33 1.411 S. aureus - MRSA 30 1.312 C. freundii 24 1.013 M. morganii 18 0.814 C. koseri 11 0.515 S. marcescens 9 0.416 E. aerogenes 8 0.317 Klebsiella spp. 8 0.318 S. saprophyticus 7 0.319 P. vulgaris 4 0.220 S. maltophilia 3 0.1
Other 36 1.62310
Rank Organism n % of Total1 S. aureus - MSSA 387 34.92 S. aureus - MRSA 134 12.13 P. aeruginosa 103 9.34 E. coli 97 8.75 S. pyogenes 69 6.26 Enterococcus spp. 47 4.27 CNS / S. epidermidis 36 3.28 E. cloacae 35 3.29 K. pneumoniae 31 2.810 S. agalactiae 28 2.511 P. mirabilis 13 1.212 K. oxytoca 10 0.913 S. marcescens 10 0.914 S. maltophilia 10 0.915 E. faecalis 9 0.816 C. freundii 8 0.717 BHS gr G 8 0.718 E. faecium 7 0.619 M. morganii 6 0.520 H. influenzae 6 0.5
Other 56 5.01110
Hospital ClinicRank Organism n % of Total
1 E. coli 445 19.82 S. aureus - MSSA 392 17.43 P. aeruginosa 270 12.04 S. pneumoniae 215 9.65 H. influenzae 152 6.86 CNS / S. epidermidis 99 4.47 K. pneumoniae 77 3.48 S. aureus - MRSA 71 3.29 Enterococcus spp. 64 2.810 S. maltophilia 49 2.211 M. catarrhalis 48 2.112 E. cloacae 36 1.613 S. marcescens 30 1.314 S. agalactiae 27 1.215 P. mirabilis 26 1.216 E. faecalis 25 1.117 S. pyogenes 23 1.018 K. oxytoca 23 1.019 C. freundii 14 0.620 H. parainfluenzae 11 0.5
Other 152 6.82249
Emergency RoomRank Organism n % of Total
1 E. coli 1101 30.02 S. aureus - MSSA 512 13.93 S. pneumoniae 400 10.94 K. pneumoniae 206 5.65 P. aeruginosa 155 4.26 S. aureus - MRSA 154 4.27 H. influenzae 144 3.98 S. pyogenes 120 3.39 CNS / S. epidermidis 107 2.910 S. agalactiae 76 2.111 Enterococcus spp. 69 1.912 P. mirabilis 67 1.813 E. faecalis 60 1.614 E. cloacae 43 1.215 K. oxytoca 43 1.216 S. viridans 42 1.117 BHS gr G 27 0.718 M. catarrhalis 25 0.719 M. morganii 21 0.620 S. marcescens 20 0.5
Other 284 7.73676
ICURank Organism n % of Total
1 S. aureus - MSSA 288 13.52 S. pneumoniae 249 11.73 E. coli 235 11.04 P. aeruginosa 171 8.05 CNS / S. epidermidis 150 7.06 K. pneumoniae 143 6.77 S. aureus - MRSA 122 5.78 H. influenzae 97 4.59 E. cloacae 82 3.810 Enterococcus spp. 49 2.311 S. marcescens 48 2.212 E. faecalis 47 2.213 S. maltophilia 44 2.114 K. oxytoca 43 2.015 C. albicans 40 1.916 M. catarrhalis 32 1.517 E. faecium 24 1.118 S. agalactiae 21 1.019 P. mirabilis 20 0.920 E. aerogenes 18 0.8
Other 214 10.02137
Medical WardRank Organism n % of Total
1 E. coli 852 21.92 S. aureus - MSSA 465 12.03 P. aeruginosa 325 8.44 S. pneumoniae 316 8.15 K. pneumoniae 263 6.86 S. aureus - MRSA 222 5.77 CNS / S. epidermidis 201 5.28 Enterococcus spp. 165 4.29 H. influenzae 124 3.210 E. faecalis 94 2.411 E. cloacae 79 2.012 S. marcescens 66 1.713 P. mirabilis 62 1.614 S. agalactiae 57 1.515 C. albicans 53 1.416 K. oxytoca 51 1.317 S. maltophilia 43 1.118 E. faecium 42 1.119 S. viridans 42 1.120 S. pyogenes 30 0.8
Other 348 9.03900
Surgical WardRank Organism n % of Total
1 E. coli 201 16.82 S. aureus - MSSA 171 14.33 S. aureus - MRSA 88 7.34 P. aeruginosa 85 7.15 K. pneumoniae 83 6.96 S. pneumoniae 70 5.87 Enterococcus spp. 64 5.38 CNS / S. epidermidis 48 4.09 H. influenzae 41 3.410 E. cloacae 40 3.311 E. faecalis 31 2.612 P. mirabilis 29 2.413 E. faecium 22 1.814 C. albicans 18 1.515 K. oxytoca 16 1.316 S. pyogenes 16 1.317 S. marcescens 13 1.118 S. maltophilia 12 1.019 M. catarrhalis 12 1.020 C. glabrata 12 1.0
Other 129 10.81201
Dr. D. Roscoe Vancouver Hospital Vancouver BC Dr. S. Poutanen Mount Sinai Hospital Toronto ONDr. R. Rennie University of Alberta Hospitals Edmonton AB Dr. F. Chan Children's Hosp. of Eastern Ontario Ottawa ONDr. J. Blondeau Royal University Hospital Saskatoon SK Dr. M. Laverdiere Hopital Maisonneuve-Rosemont Montreal QCDrs. Hoban / Zhanel Health Sciences Centre Winnipeg MB Dr. V. Loo Montreal General Hospital Montreal QCDr. Z. Hussain London Health Sciences Centre London ON Dr. V. Loo Royal Victoria Hospital (2007 only) Montreal QCDr. C. Lee St. Joseph's Hospital (2007 only) Hamilton ON Dr. R. Davidson Queen Elizabeth II HSC Halifax NS
Most Common Pathogens by Ward Type
% Sus % Int % Res MIC50 MIC90 Minimum MaximumAmikacin 99.5% 0.3% 0.2% ≤ 2 4 ≤ 2 > 64Amoxicillin Clavulanate 95.4% 3.9% 0.8% 4 8 0.5 > 32Cefazolin 84.4% 3.1% 12.5% 2 64 0.5 > 128Cefepime 96.0% 2.2% 1.8% ≤ 1 ≤ 1 ≤ 1 > 32Cefoxitin 91.3% 3.7% 5.0% 4 8 ≤ 0.06 > 32Ceftazidime 95.9% 0.6% 3.5% ≤ 0.5 1 ≤ 0.5 > 32Ceftobiprole* 95.0% 0.4% 7.6% ≤ 1 ≤ 1 ≤ 1 > 32Ceftriaxone 91.4% 1.5% 7.1% ≤ 1 2 ≤ 1 > 64Ciprofloxacin 76.2% 0.3% 23.5% ≤ 0.06 > 16 ≤ 0.06 > 16Colistin No breakpoints defined 0.5 1 ≤ 0.06 > 16Ertapenem 100.0% ≤ 0.06 ≤ 0.06 ≤ 0.06 1Gentamicin 89.3% 0.4% 10.3% ≤ 0.5 16 ≤ 0.5 > 32Levofloxacin 76.5% 0.7% 22.8% ≤ 0.06 16 ≤ 0.06 > 32Meropenem 100.0% ≤ 0.06 ≤ 0.06 ≤ 0.06 0.12Moxifloxacin No breakpoints defined ≤ 0.06 > 16 ≤ 0.06 > 16Nitrofurantoin 96.5% 2.4% 1.1% 16 32 0.25 > 256Piperacillin Tazobactam 97.3% 1.4% 1.3% 2 4 ≤ 1 256Tigecycline* 99.8% 0.2% 0.5 1 0.12 4Trimethoprim Sulfa 73.0% 27.0% ≤ 0.12 > 8 ≤ 0.12 > 8
Susceptibility Range
*Interpretive breakpoints defined by Health Canada (ceftobiprole) or FDA (tigecycline) where applicable
E.coli (2833)
% Sus % Int % Res MIC50 MIC90 Minimum MaximumAmikacin 88.6% 5.4% 6.1% 8 32 ≤ 2 > 64Cefepime 72.4% 17.6% 10.0% 4 32 ≤ 1 > 32Ceftazidime 88.2% 2.7% 9.1% 2 16 ≤ 0.5 > 32Ceftobiprole No breakpoints defined 4 16 0.25 > 32Ciprofloxacin 69.5% 8.8% 21.8% 0.5 8 ≤ 0.06 > 16Colistin 90.8% 8.0% 1.2% 2 2 0.5 > 16Gentamicin 64.2% 18.1% 17.7% 4 16 ≤ 0.5 > 32Levofloxacin 62.6% 12.6% 24.8% 1 16 ≤ 0.06 > 32Meropenem 88.8% 4.1% 7.2% 0.5 8 ≤ 0.06 > 32Piperacillin Tazobactam 92.5% 7.5% 4 64 ≤ 1 > 512
Susceptibility Range
P. aeruginosa (1006)
% Sus % Int % Res MIC50 MIC90 Minimum MaximumCefazolin 100.0%** 128 > 128 2 > 128Cefepime 100.0%** > 32 > 32 4 > 32Cefoxitin 100.0%** > 32 > 32 1 > 32Ceftazidime 100.0%** > 32 > 32 16 > 32Ceftobiprole* 100.0% 1 2 0.5 4Ceftriaxone 100.0%** > 64 > 64 16 > 64Ciprofloxacin 11.3% 0.2% 88.6% > 16 > 16 0.25 > 16Clarithromycin 10.8% 0.2% 89.0% > 32 > 32 ≤ 0.03 > 32Clindamycin 40.6% 0.2% 59.2% > 8 > 8 ≤ 0.12 > 8Daptomycin 100.0% 0.12 0.25 0.06 1Ertapenem 100.0%** 8 > 32 0.5 > 32Levofloxacin 12.0% 88.0% > 32 > 32 0.12 > 32Linezolid 100.0% 2 2 ≤ 0.12 4Meropenem 100.0%** 8 32 0.12 > 32Moxifloxacin 12.0% 0.3% 87.7% 8 > 16 ≤ 0.06 > 16Nitrofurantoin 100.0% 16 16 8 32Piperacillin Tazobactam 100.0%** 64 128 ≤ 1 512Tigecycline* 100.0% 0.25 0.25 0.12 0.25Trimethoprim Sulfa 88.6% 11.4% ≤ 0.12 8 ≤ 0.12 > 8Vancomycin 99.8% 0.2% 1 1 ≤ 0.5 4*Interpretive breakpoints defined by Health Canada (ceftobiprole) or FDA (tigecycline) where applicable**Based on oxacillin susceptibility
Susceptibility Range
S. aureus - MRSA (657)
Wound / IV SiteUrine
Blood Respiratory
