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. 2010 Aug 30;54(11):4684–4693. doi: 10.1128/AAC.00469-10

Prevalence of Antimicrobial-Resistant Pathogens in Canadian Hospitals: Results of the Canadian Ward Surveillance Study (CANWARD 2008) ▿

George G Zhanel 1,2,3,*, Melanie DeCorby 1,3, Heather Adam 1,3, Michael R Mulvey 1,6, Melissa McCracken 6, Philippe Lagacé-Wiens 1,4, Kimberly A Nichol 3, Aleksandra Wierzbowski 1,3, Patricia J Baudry 1,3, Franil Tailor 1,3, James A Karlowsky 1,3, Andrew Walkty 1,2,3, Frank Schweizer 1,5, Jack Johnson 7; the Canadian Antimicrobial Resistance Alliance, Daryl J Hoban 1,3
PMCID: PMC2976152  PMID: 20805395

Abstract

A total of 5,282 bacterial isolates obtained between 1 January and 31 December 31 2008, inclusive, from patients in 10 hospitals across Canada as part of the Canadian Ward Surveillance Study (CANWARD 2008) underwent susceptibility testing. The 10 most common organisms, representing 78.8% of all clinical specimens, were as follows: Escherichia coli (21.4%), methicillin-susceptible Staphylococcus aureus (MSSA; 13.9%), Streptococcus pneumoniae (10.3%), Pseudomonas aeruginosa (7.1%), Klebsiella pneumoniae (6.0%), coagulase-negative staphylococci/Staphylococcus epidermidis (5.4%), methicillin-resistant S. aureus (MRSA; 5.1%), Haemophilus influenzae (4.1%), Enterococcus spp. (3.3%), Enterobacter cloacae (2.2%). MRSA comprised 27.0% (272/1,007) of all S. aureus isolates (genotypically, 68.8% of MRSA were health care associated [HA-MRSA] and 27.6% were community associated [CA-MRSA]). Extended-spectrum β-lactamase (ESBL)-producing E. coli occurred in 4.9% of E. coli isolates. The CTX-M type was the predominant ESBL, with CTX-M-15 the most prevalent genotype. MRSA demonstrated no resistance to ceftobiprole, daptomycin, linezolid, telavancin, tigecycline, or vancomycin (0.4% intermediate intermediate resistance). E. coli demonstrated no resistance to ertapenem, meropenem, or tigecycline. Resistance rates with P. aeruginosa were as follows: colistin (polymyxin E), 0.8%; amikacin, 3.5%; cefepime, 7.2%; gentamicin, 12.3%; fluoroquinolones, 19.0 to 24.1%; meropenem, 5.6%; piperacillin-tazobactam, 8.0%. A multidrug-resistant (MDR) phenotype occurred frequently in P. aeruginosa (5.9%) but uncommonly in E. coli (1.2%) and K. pneumoniae (0.9%). In conclusion, E. coli, S. aureus (MSSA and MRSA), P. aeruginosa, S. pneumoniae, K. pneumoniae, H. influenzae, and Enterococcus spp. are the most common isolates recovered from clinical specimens in Canadian hospitals. The prevalence of MRSA was 27.0% (of which genotypically 27.6% were CA-MRSA), while ESBL-producing E. coli occurred in 4.9% of isolates. An MDR phenotype was common in P. aeruginosa.

The prevalence of antimicrobial-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA; either community associated [CA-MRSA] or health care associated [HA-MRSA]), vancomycin-resistant enterococci (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, is increasing in all regions of Canada, the United States, and globally (2, 3, 5, 6, 12, 19, 21, 24, 26, 27, 28, 30, 35, 37, 38). These organisms commonly display a multidrug-resistant (MDR) phenotype (concomitant resistance to ≥3 different antimicrobial classes), further limiting treatment options (2, 3, 19, 21, 24, 35, 37-39).

The purpose of the Canadian Ward Surveillance Study (CANWARD) study was to assess the prevalence of pathogens, including the resistance genotypes of MRSA, VRE, and ESBL isolates, causing infections in Canadian hospitals as well as their antimicrobial resistance patterns. The CANWARD study is the first ongoing, national, prospective surveillance study assessing antimicrobial resistance in Canadian hospitals. The results of CANWARD 2007 were previously published (39), and the data are available on the official website of the Canadian Antimicrobial Resistance Alliance (CARA; www.can-r.ca).

(This paper was presented in part at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy, 2009, in San Francisco, CA.)

MATERIALS AND METHODS

Bacterial isolates.

The CANWARD 2008 study included 10 medical centers from all regions of Canada (see Acknowledgments and www.can-r.ca). From 1 January to 31 December 2008, inclusive, each center collected and submitted clinical isolates from patients attending hospital clinics, emergency rooms (ER), medical and surgical wards, and intensive care units (ICUs). Each center was asked to submit clinically significant isolates (unique, consecutive; 1 organism/infection site per patient) from blood (240 isolates collected [20 consecutive samples/month for each of the 12 months]), respiratory (150), urine (100), and wound (50) infections. Criteria for exclusion were the following: surveillance swabs; eye, ear, nose and throat swabs; duplicate swabs (i.e., not unique isolates); polymicrobial cultures. Additionally, anaerobic organisms and fungal organisms, except Candida species from blood cultures, were excluded. All organisms were identified and deemed clinically significant at the originating center based on local site criteria. In CANWARD 2008, 5,282 isolates were collected from 4,260 patients (1.24 isolates/patient). Isolates were shipped to the coordinating laboratory (Health Sciences Centre, Winnipeg, Canada) on Amies charcoal swabs, subcultured onto appropriate media, and stocked in skim milk at −80°C until MIC testing was carried out.

Antimicrobial susceptibility testing.

Following two subcultures from frozen stock, the in vitro activities of amikacin, amoxicillin-clavulanate, cefazolin, ceftazidime, ceftriaxone, cefepime, ceftobiprole, ciprofloxacin, clarithromycin, clindamycin, colistin (polymyxin E), daptomycin, doripenem, ertapenem, gentamicin, levofloxacin, linezolid, meropenem, moxifloxacin, nitrofurantoin, piperacillin-tazobactam, telavancin, tigecycline, trimethoprim-sulfamethoxazole (SXT), and vancomycin were determined by broth microdilution in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines (9). Susceptibility testing was not performed for all antimicrobial agents due to a lack of space on the susceptibility panels. The MICs were determined using 96-well custom-designed broth microtiter panels, which were made in-house with antimicrobial agents obtained as laboratory-grade powders from their respective manufacturers, and stock solutions were prepared and dilutions made as described by CLSI (9). The microtiter panels were inoculated to achieve a final concentration of approximately 5 × 105 CFU/ml and incubated in ambient air prior to reading. Colony counts were performed periodically to confirm that the appropriate inocula were used. Quality control (QC) was performed using ATCC QC organisms S. pneumoniae 49619, S. aureus 29213, Enterobacter faecalis 29212, E. coli 25922, and P. aeruginosa 27853.

CLSI breakpoints were used for all antimicrobial agent-organism combinations for which interpretative criteria were available (10). For agents without CLSI interpretative criteria, FDA and Health Canada breakpoints were applied. The following FDA breakpoints (susceptible [S], intermediate [I], and resistant [R]) were used for tigecycline: S. aureus (methicillin susceptible [MSSA] and MRSA), ≤0.5 μg/ml (S); E. faecalis (vancomycin susceptible), ≤0.25 μg/ml (S); Enterobacteriaceae, ≤2 μg/ml (S), 4 μg/ml (I), and ≥8 μg/ml (R). The following Health Canada interpretive breakpoints were used for ceftobiprole, which is commercially available in Canada: S. aureus (MSSA and MRSA), ≤4.0 μg/ml (S); Enterobacteriaceae, ≤1 μg/ml (S), 2 μg/ml (I), and ≥4 μg/ml (R). The following FDA breakpoint for telavancin and S. aureus (MSSA and MRSA) was used: ≤1 μg/ml (S).

Characterization of MRSA, ESBL-producing E. coli, and VRE. (i) MRSA.

Potential MRSA isolates were confirmed using the CLSI disk diffusion method with cefoxitin and by multiplex PCR of the mecA and nuc genes. All MRSA isolates were tested by PCR for the Panton-Valentine leukocidin gene (pvl). Additionally, all MRSA isolates were typed using pulsed-field gel electrophoresis (PFGE) and spa typing following the Canadian standardized protocol to assess whether the isolates were community associated or health care associated (8, 15, 23-25). PFGE fingerprints were analyzed with BioNumerics version 3.5 (Applied Maths, Austin, TX), and strain relatedness was determined as previously described (33). The PFGE fingerprints were compared to the national MRSA fingerprint database and were grouped into 1 of 10 Canadian epidemic MRSA strain types (CMRSA-1 to CMRSA-10) as previously described (23). In the CANWARD study, CA-MRSA and HA-MRSA were defined genotypically; MRSA isolates with a CMRSA-7 (USA400/MW2) or CMRSA-10 (USA300) genotype were labeled as CA-MRSA, while all other genotypes (e.g., CMRSA-1 [USA600], CMRSA-2 [USA100], CMRSA-4 [USA200], etc.) were labeled as HA-MRSA (23, 24, 38).

(ii) ESBL.

Any E. coli or Klebsiella spp. with a ceftriaxone and/or ceftazidime MIC of ≥1 μg/ml was identified as a potential ESBL producer as specified by CLSI (10, 22). The potential ESBL-producing organisms were phenotypically confirmed using the CLSI confirmatory method (10). PCR and DNA sequence analysis were used to identify blaSHV, blaTEM, and blaCTX-M genes among all ESBL-producing E. coli and Klebsiella species isolates, as previously described (2, 3, 27).

(iii) VRE.

Potential VRE isolates were confirmed using CLSI vancomycin disk diffusion testing and underwent vanA and vanB PCR as well as PFGE typing to assess genetic similarity, as previously described (12, 36).

Statistical analyses.

To analyze factors associated with antimicrobial resistance, all organisms were classified by the number of antimicrobial classes (0 to ≥5) to which they displayed resistance, regardless of species. Only antimicrobial-organism combinations for which CLSI interpretative criteria exist were considered in this analysis. Univariate χ2 analysis was used to evaluate statistically significant associations between the number of antimicrobial classes to which resistance was observed and gender, age, geographic region, inpatient status, and invasive (blood culture) isolates. Factors found to have a P value of <0.10 in the univariate analysis were included in a full factorial ordinal logistic regression model to determine the variables that were independently associated with resistance. Finally, a separate nominal logistic regression model using multidrug resistance (≥3 classes) in Gram-negative organisms and pan-susceptibility (susceptibility to all antimicrobial classes tested) in all organisms as the response variables was also considered. All statistical analyses were done using JMP 8.0 software (SAS Institute, Cary, NC).

RESULTS

Patient demographics and specimen types.

A total of 5,282 isolates recovered from clinical specimens were collected from hospitals across Canada as part of CANWARD 2008. Overall, 53.7% (2,838/5,282) of the isolates were collected from males. The patient age breakdown was as follows: ≤17 years, 14.4% (760/5,282); 18 to 64 years, 44.9% (2,370/5,282); ≥65 years, 40.7% (2,152/5,282). With regard to specimen source, 30.5% (1,612/5,282) of the organisms were obtained from respiratory specimens, 41.5% (2,194/5,282) from blood, 9.3% (493/5,282) from wounds, and 18.6% (983/5,282) from urine.

Predominant organisms isolated in Canadian hospitals.

The 20 most commonly isolated organisms in hospitals across Canada are listed in Table 1. For Gram-positive cocci, S. aureus (MSSA), S. pneumoniae, MRSA, Enterococcus spp., and coagulase-negative staphylococci(CNS)/Staphylococcus epidermidis collectively represented 38.0% of all isolates. For Gram-negative bacilli, E. coli, P. aeruginosa, Klebsiella pneumoniae, Haemophilus influenzae, and Enterobacter cloacae represented 40.8% of all organisms.

TABLE 1.

The 20 most common organisms isolated from Canadian hospitals

Ranking Organism No. of isolates % of total
1 Escherichia coli 1,132 21.4
2 Staphylococcus aureus MSSA 735 13.9
3 Streptococcus pneumoniae 544 10.3
4 Pseudomonas aeruginosa 373 7.1
5 Klebsiella pneumoniae 316 6.0
6 CNS/S. epidermidis 283 5.4
7 Staphylococcus aureus MRSA 272 5.1
8 Haemophilus influenzae 214 4.1
9 Enterococcus spp. 176 3.3
10 Enterobacter cloacae 114 2.2
11 Enterococcus faecalis 101 1.9
12 Streptococcus pyogenes 97 1.8
13 Proteus mirabilis 85 1.6
14 Klebsiella oxytoca 76 1.4
15 Streptococcus agalactiae 73 1.4
16 Serratia marcescens 69 1.3
17 Stenotrophomonas maltophilia 57 1.1
18 Moraxella catarrhalis 52 1.0
19 Enterococcus faecium 49 0.9
20 Viridans group Streptococci 44 0.8
Othera 420 8.0
Total 5,282 100.0
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a

Other organisms included the following: Acinetobacter spp., Aeromonas spp., Alcaligenes spp., Bacillus spp., Brevibacterium spp., Candida spp., Cedecea spp., Chryseobacterium spp., Citrobacter spp., Corynebacterium spp., Enterobacter spp., Enterococcus spp., Escherichia spp., Gemella spp., Granulicatella spp., Haemophilus spp., Hafnia spp., Klebsiella spp., Listeria spp., Micrococcus spp., Moraxella spp., Morganella spp., Neisseria spp., Pantoea spp., Pasteurella spp., Proteus spp., Providencia spp., Pseudomonas spp., Ralstonia spp., Salmonella spp., Serratia spp., Staphylococcus spp., and Streptococcus spp.

Predominant organisms isolated by specimen site.

Table 2 describes the 10 most commonly isolated microorganisms recovered from the four evaluated specimen sources (respiratory, blood, wounds, and urine). S. pneumoniae, S. aureus (MSSA), and P. aeruginosa were the most commonly isolated pathogens from respiratory tract specimens (>50% of isolates). Among blood culture isolates, E. coli, S. aureus (MSSA), and coagulase-negative staphylococci/S. epidermidis were the most predominant. S. aureus (MSSA and MRSA) was the most commonly isolated organism from wound cultures (∼50% of wound pathogens). Among urinary tract specimens, E. coli was the predominant pathogen (51.9%), while enterococci (14.5%) and K. pneumoniae (10%) were also frequently identified.

TABLE 2.

The 10 most common organisms isolated in Canadian hospitals, by specimen site

Site (% of total isolates) and ranking Organism No. of isolates % of total
Respiratory (30.5)
    1 S. pneumoniae 423 26.2
    2 S. aureus MSSA 237 14.7
    3 P. aeruginosa 217 13.5
    4 H. influenzae 201 12.5
    5 S. aureus MRSA 91 5.6
    6 K. pneumoniae 66 4.1
    7 E. coli 60 3.7
    8 M. catarrhalis 52 3.2
    9 S. maltophilia 42 2.6
    10 S. marcescens 32 2.0
    Other 191 11.9
    Total 1,612 100.0
Blood (41.5)
    1 E. coli 522 23.8
    2 S. aureu MSSA 299 13.6
    3 CNS /S. epidermidis 256 11.7
    4 K. pneumoniae 139 6.3
    5 S. pneumoniae 121 5.5
    6 S. aureus MRSA 109 5.0
    7 E. faecalis 94 4.3
    8 P. aeruginosa 81 3.7
    9 E. cloacae 48 2.2
    10 S. agalactiae 45 2.1
    Other 480 21.8
    Total 2,194 100.0
Wounds (9.3)
    1 S. aureus MSSA 184 37.3
    2 S. aureus MRSA 58 11.8
    3 E. coli 40 8.1
    4 P. aeruginosa 40 8.1
    5 S. pyogenes 37 7.5
    6 Enterococcus spp. 22 4.5
    7 E. cloacae 14 2.8
    8 K. pneumoniae 13 2.6
    9 CNS/S. epidermidis 10 2.0
    10 S. agalactiae 8 1.6
    Other 67 13.7
    Total 493 100.0
Urine (18.6)
    1 E. coli 510 51.9
    2 Enterococcus spp. 143 14.5
    3 K. pneumoniae 98 10.0
    4 P. mirabilis 46 4.7
    5 P. aeruginosa 35 3.6
    6 E. cloacae 22 2.2
    7 K. oxytoca 17 1.7
    8 CNS/S. epidermidis 16 1.6
    9 S. aureus MSSA 15 1.5
    10 S. aureus MRSA 14 1.4
    Other 67 6.9
    Total 983 100.0
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Characteristics of MRSA.

Twenty-seven percent (272/1,007) of all S. aureus isolates were MRSA. The prevalence of MRSA varied geographically: British Columbia/Alberta, 31.6%; Quebec/Maritimes, 30.9%; Ontario, 25.7%; Manitoba/Saskatchewan, 19.3%. Genotypically (as determined by PFGE), 68.8% of MRSA were HA-MRSA and 27.6% were CA-MRSA (3.8% of MRSA could not be genotypically classified). CMRSA-10/USA300 represented 80.0%, whereas 20.0% of the CA-MRSA were CMRSA-7/USA400. PFGE patterns among HA-MRSA included CMRSA-2/USA100/800 (81.9%), CMRSA-3 or CMRSA-6 (12.8%), CMRSA-1/USA600 (1.6%), CMRSA-5/USA500 (1.6%), CMRSA-8 (1.1%), CMRSA-4/USA200 (0.5%), and CMRSA-9 (0.5%). PVL was detected in 85.3% of CA-MRSA and 0.5% of HA-MRSA isolates.

Characteristics of ESBL-producing E. coli and K. pneumoniae.

Of the E. coli isolates tested, 4.9% (55/1,132) were ESBL producing. The proportion of E. coli isolates producing ESBLs varied by medical unit: 2.5% in hospital clinics, 2.9% in surgical wards, 4.6% in emergency rooms, 5.9% in medical wards, and 8.0% in intensive care units. The prevalence of ESBL-producing E. coli isolates varied geographically: British Columbia/Alberta, 7.6%; Ontario, 5.8%; Manitoba/Saskatchewan, 4.7%; Quebec/Maritimes, 2.4%. Of the 55 ESBL-producing E. coli, 49 (89.1%) carried ESBL genes from the CTX-M group (39 [70.9%] blaCTX-M-15, 8 [14.5%] blaCTX-M-14, and 2 [3.6%] blaCTX-M-27), 2 (3.6%) carried blaSHV2a, 1 (2.2%) carried blaTEM-12, and for 3 (5.5%) the ESBL gene was unknown. An MDR phenotype was observed in 76.4% of the ESBL-producing E. coli. ESBL production was detected in 3.2% (10/316) of the K. pneumoniae isolates, with Ontario recording 50% (5/10) of all strains. An MDR phenotype was observed in 80.0% of the ESBL-producing K. pneumoniae.

Characteristics of VRE.

Among the 320 enterococci, 10 (3.1%) were VRE. All VRE detected were E. faecium and displayed the vanA genotype.

Antimicrobial susceptibility testing.

Antimicrobial resistance rates for the most common Gram-positive cocci based on specimen source are listed in Table 3. Among MSSA, no resistance was observed to ceftobiprole (MIC90, 0.5 μg/ml [data not shown]), daptomycin, linezolid, telavancin (MIC90, 0.5 μg/ml [data not shown]), tigecycline, or vancomycin. The MIC90s (in μg/ml) to dalbavancin and oritavancin were 0.06 and 0.5, respectively (data not shown). Resistance rates with MSSA were as follows: clarithromycin, 23.5%; clindamycin, 6.5%; fluoroquinolones, 7.5 to 9.2%; SXT, 1.2% (Table 3). With MRSA, no resistance was observed with ceftobiprole (MIC90, 2 μg/ml [data not shown]), daptomycin, linezolid, telavancin (MIC90, 0.5 μg/ml [data not shown]), tigecycline, and vancomycin (0.4% intermediate). The MIC90s (in μg/ml) to dalbavancin and oritavancin were 0.06 and 0.5, respectively (data not shown). Resistance rates with MRSA were as follows: clarithromycin, 85.7%; clindamycin, 55.5%; fluoroquinolones, 86.4 to 87.1%; SXT, 10.3% (Table 3). With S. pneumoniae, no resistance was observed to vancomycin, linezolid, or ertapenem. The MIC90s (in μg/ml) to dalbavancin, oritavancin, and telavancin were ≤0.03, 0.004, and ≤0.03, respectively (data not shown). Resistance rates with S. pneumoniae were as follows: fluoroquinolones, 1.0 to 4.7%; ceftriaxone, 0.2%; meropenem, 1.7%; clarithromycin, 17.5%; clindamycin, 8.2%; SXT, 10.0% (Table 3). Resistance rates for tested antimicrobials were higher in S. pneumoniae isolates obtained from respiratory versus blood specimens (Table 3).

TABLE 3.

Resistance rates for the most common Gram-positive cocci isolated from Canadian hospitals, based on specimen sourcea

Organism and source (n) % I/% R
CFZ CPM CTR PTZ ETP MER CIPc LEV MXF CLR CD LZD TGC SXT FD DAP VAN
S. aureus
    MSSA
        All (735) 0/0 0/0 0/0 0/0 0/0 0/0 3.4/9.2 0.4/8.0 0.7/7.5 0.1/23.5 0.9/6.5 0/0 0/0 0/1.2 0/0 0/0 0/0
        Blood (299) 0/0 0/0 0/0 0/0 0/0 0/0 2.3/8.0 0/7.4 0.3/7.0 0/22.4 0/5.0 0/0 0/0 0/0.7 0/0 0/0 0/0
        Urine (15) NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA
        Wound (184) 0/0 0/0 0/0 0/0 0/0 0/0 1.6/7.1 0.5/5.4 1.1/4.3 0/21.2 0.5/7.1 0/0 0/0 0/2.7 0/0 0/0 0/0
        Respiratory (237) 0/0 0/0 0/0 0/0 0/0 0/0 6.3/11.0 0.8/9.3 0.8/8.9 0.4/26.6 2.5/6.7 0/0 0/0 0/0.8 0/0 0/0 0/0
    MRSA
        All (272) 0/100b 0/100b 0/100b 0/100b 0/100b 0/100b 0/87.1 0/86.4 0/86.4 0.4/85.7 0/55.5 0/0 0/0 0/10.3 0/0 0/0 0.4/0
        Blood (109) 0/100b 0/100b 0/100b 0/100b 0/100b 0/100b 0/81.6 0/81.6 0/81.6 0.9/83.5 0/51.4 0/0 0/0 0/11.9 0/0 0/0 0.9/0
        Urine (14) NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA
        Wound (58) 0/100b 0/100b 0/100b 0/100b 0/100b 0/100b 0/81.0 0/77.6 0/77.6 0/81.0 0/36.2 0/0 0/0 0/5.2 0/0 0/0 0/0
        Respiratory (91) 0/100b 0/100b 0/100b 0/100b 0/100b 0/100b 0/95.6 0/95.6 0/95.6 0/89.0 0/71.4 0/0 0/0 0/11.0 0/0 0/0 0/0
S. pneumoniae
    All (544) − − 0.6/0.2 − 0/0 3.3/1.7 4.7 0.4/1.2 0.4/1.0 2.1/17.5 0.4/8.2 0/0 − 7.5/10.0 − − 0/0
    Blood (121) − − 0/0 − 0/0 0.9/0.9 0.0 0/0 0/0 1.7/12.3 0/7.0 0/0 − 6.8/7.7 − − 0/0
    Urine (NA) − − NA − NA NA NA NA NA NA NA NA − NA − − NA
    Wound (NA) − − NA − NA NA NA NA NA NA NA NA − NA − − NA
    Respiratory (423) − − 0.7/0.2 − 0/0 4.0/2.0 6.0 0.5/1.5 0.5/1.2 2.2/18.9 0.5/8.5 0/0 − 7.6/10.6 − − 0/0
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a

I, intermediate; R, resistant; NA, no isolates met criteria or there were insufficient numbers for analysis (n < 40); −, no defined breakpoints; CFZ, cefazolin; CPM, cefepime; CTR, ceftriaxone; PTZ, piperacillin-tazobactam; ETP, ertapenem; MER, meropenem; CIP, ciprofloxacin; LEV, levofloxacin; MXF, moxifloxacin; CLR, clarithromycin; CD, clindamycin; LZD, linezolid; TGC, tigecycline; FD, nitrofurantoin; DAP, daptomycin; VAN, vancomycin.

b

Based on oxacillin susceptibility.

c

For S. pneumoniae, only the percentage of resistant isolates (≥4 μg/ml) for ciprofloxacin is shown.

Resistance rates for the most common Gram-positive cocci based on hospital ward location are listed in Table 4. S. aureus (MSSA and MRSA) resistance rates for fluoroquinolones, clarithromycin, clindamycin, and SXT were not influenced by ward location. With S. pneumoniae, resistance rates with fluoroquinolones, clarithromycin, and clindamycin tended to be higher on medical wards than other hospital locations.

TABLE 4.

Resistance rates for the most common Gram-positive cocci isolated from Canadian hospitals, based on hospital locationa

Organism and location (n) % I/% R
CFZ CPM CTR PTZ ETP MER CIPc LEV MXF CLR CD LZD TGC SXT FD DAP VAN
S. aureus
    MSSA
        All (735) 0/0 0/0 0/0 0/0 0/0 0/0 3.4/9.2 0.4/8.0 0.7/7.5 0.1/23.5 0.9/6.5 0/0 0/0 0/1.2 0/0 0/0 0/0
        Clinic (152) 0/0 0/0 0/0 0/0 0/0 0/0 9.9/7.9 1.3/5.9 0.7/5.9 0/27.0 3.3/7.2 0/0 0/0 0/1.3 0/0 0/0 0/0
        ER (211) 0/0 0/0 0/0 0/0 0/0 0/0 1.9/9.0 0/8.5 0.5/8.1 0.5/25.1 0/6.2 0/0 0/0 0/0.9 0/0 0/0 0/0
        ICU (105) 0/0 0/0 0/0 0/0 0/0 0/0 0.9/13.3 0/11.4 0/11.4 0/22.9 0/6.7 0/0 0/0 0/1.9 0/0 0/0 0/0
        Medical (178) 0/0 0/0 0/0 0/0 0/0 0/0 1.1/8.4 0.6/7.3 0.6/6.7 0/19.7 1.1/6.7 0/0 0/0 0/1.1 0/0 0/0 0/0
        Surgical (89) 0/0 0/0 0/0 0/0 0/0 0/0 3.4/9.0 0/7.9 2.2/5.6 0/22.5 0/5.6 0/0 0/0 0/1.1 0/0 0/0 0/0
    MRSA
        All (272) 0/100b 0/100b 0/100b 0/100b 0/100b 0/100b 0/87.1 0/86.4 0/86.4 0.4/85.7 0/55.5 0/0 0/0 0/10.3 0/0 0/0 0.4/0
        Clinic (24) NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA
        ER (69) 0/100b 0/100b 0/100b 0/100b 0/100b 0/100b 0/88.4 0/88.4 0/88.4 0/85.5 0/37.7 0/0 0/0 0/2.9 0/0 0/0 1.4/0
        ICU (50) 0/100b 0/100b 0/100b 0/100b 0/100b 0/100b 0/86.0 0/86.0 0/86.0 2.0/82.0 0/62.0 0/0 0/0 0/22.0 0/0 0/0 0/0
        Medical (85) 0/100b 0/100b 0/100b 0/100b 0/100b 0/100b 0/88.2 0/88.2 0/88.2 0/87.1 0/67.1 0/0 0/0 0/8.2 0/0 0/0 0/0
        Surgical (44) 0/100b 0/100b 0/100b 0/100b 0/100b 0/100b 0/86.4 0/81.8 0/81.8 0/90.9 0/56.8 0/0 0/0 0/15.9 0/0 0/0 0/0
S. pneumoniae
    All (544) − − 0.6/0.2 − 0/0 3.3/1.7 4.7 0.4/1.2 0.4/1.0 2.1/17.5 0.4/8.2 0/0 − 7.5/10.0 − − 0/0
    Clinic (93) − − 0/0 − 0/0 4.7/3.5 5.9 0/1.2 0/1.2 0/16.5 0/7.1 0/0 − 2.3/16.1 − − 0/0
    ER (152) − − 0/0 − 0/0 0.7/1.4 2.8 0/0.7 0/0.7 2.1/13.4 1.4/7.0 0/0 − 6.8/4.8 − − 0/0
    ICU (132) − − 1.6/0 − 0/0 2.4/0.8 4.0 0/0 2.4/0.8 1.6/16.0 0/7.2 0/0 − 7.9/10.3 − − 0/0
    Medical (129) − − 0.8/0.8 − 0/0 5.6/0.8 6.4 1.6/3.2 1.6/2.4 3.2/24.0 0/11.2 0/0 − 8.8/9.6 − − 0/0
    Surgical (38) − − NA − NA NA NA NA NA NA NA NA − NA − − NA
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a

I, intermediate; R, resistant; NA, no isolates met criteria or there were insufficient numbers for analysis (n < 40); −, no defined breakpoints; CFZ, cefazolin; CPM, cefepime; CTR, ceftriaxone; PTZ, piperacillin-tazobactam; ETP, ertapenem; MER, meropenem; CIP, ciprofloxacin; LEV, levofloxacin; MXF, moxifloxacin; CLR, clarithromycin; CD, clindamycin; LZD, linezolid; TGC, tigecycline; FD, nitrofurantoin; DAP, daptomycin; VAN, vancomycin.

b

Based on oxacillin susceptibility.

c

For S. pneumoniae, only the percentage of resistant isolates (≥4 μg/ml) for ciprofloxacin is shown.

For Gram-positive organisms, the ordinal logistic regression model showed increasing age (P < 0.001), inpatient status (P < 0.001), and invasive isolates (P < 0.001) were associated with higher resistance rates. The nominal logistic regression model showed that pan-susceptibility was associated with lower age (P = 0.003), outpatient status (P < 0.001), and noninvasive isolates (P < 0.001).

Antimicrobial resistance rates for the most common Gram-negative bacilli based on specimen source are listed in Table 5. With E. coli, no resistance was observed to doripenem, ertapenem, meropenem, and tigecycline. Resistance rates with E. coli against other agents were as follows: amoxicillin-clavulanate, 0.5%; cefazolin, 10.0%; cefepime, 1.6%; ceftriaxone, 4.4%; gentamicin, 9.7%; fluoroquinolones, 21.6 to 22.1%; piperacillin-tazobactam, 1.2%; SXT, 27.7%. Resistance rates with P. aeruginosa were as follows: amikacin, 3.5%; cefepime, 7.2%; gentamicin, 12.3%; fluoroquinolones, 19.0 to 24.1%; meropenem, 5.6% (meropenem MIC90, 8 μg/ml, versus doripenem MIC90, 4 μg/ml); piperacillin-tazobactam, 8.0%; colistin (polymyxin E), 0.8%. P. aeruginosa resistance rates with aminoglycosides, fluoroquinolones, and colistin were higher in isolates obtained from respiratory specimens. With K. pneumoniae, no resistance was observed to amoxicillin-clavulanate, doripenem, ertapenem, and meropenem. Resistance rates with K. pneumoniae were as follows: cefazolin, 6.3%; ceftriaxone, 1.3%; cefepime, 0.9%; fluoroquinolones, 5.1 to 7.3%; amikacin, 0.6%; gentamicin, 2.8%; piperacillin-tazobactam, 2.5%; tigecycline, 0.6%; SXT, 11.4%. K. pneumoniae resistance rates with aminoglycosides and fluoroquinolones were higher in isolates from urinary specimens.

TABLE 5.

Resistance rates for the most common Gram-negative bacilli isolated from Canadian hospitals, based on specimen sourcea

Organism and source (n) % I/% R
A/C CFZ CPM CTR FOX ETP MER PTZ AMK GEN CIP LEV MXF COL FDb SXT TGC
E. coli
    All (1132) 1.4/0.5 2.2/10.0 1.1/1.6 0.9/4.4 3.6/5.6 0/0 0/0 1.9/1.2 0.2/0.3 0.3/9.7 0.2/22.1 0.5/21.6 − − 1.9/1.1 0/27.7 0.2/0
    Blood (522) 1.0/0.2 2.7/9.8 2.1/1.0 1.1/5.0 2.9/4.8 0/0 0/0 2.1/1.0 0.2/0.6 0.2/10.5 0.2/21.6 0.6/21.3 − − 1.2/0.8 0/31.6 0/0
    Urine (510) 1.6/0.6 1.6/9.2 0.4/2.3 0.4/4.1 3.7/6.1 0/0 0/0 1.6/0.8 0/0.2 0.4/8.2 0.2/21.4 0.4/21.0 − − 2.0/1.6 0/24.3 0.4/0
    Wound (40) 0/5.0 2.5/12.5 0/0 5.0/2.5 5.0/15.0 0/0 0/0 2.5/2.5 2.5/0 2.5/7.5 0/22.5 0/22.5 − − 5.0/0 0/25.0 0/0
    Respiratory (60) 5.0/0 3.3/16.7 0/1.7 0/3.3 8.3/3.3 0/0 0/0 3.3/6.7 0/0 0/16.7 0/31.7 1.7/30.0 − − 0/0 0/25.0 0/0
P. aeruginosa
    All (373) − − 12.1/7.2 45.8/32.7 − − 4.0/5.6 0/8.0 2.7/3.5 16.6/12.3 5.6/19.0 11.3/24.1 − 7.2/0.8 − − −
    Blood (81) − − 4.9/7.4 50.6/29.6 − − 1.2/8.6 0/6.2 2.5/1.2 13.6/7.4 1.2/16.0 13.6/16.0 − 7.4/0 − − −
    Urine (35) − − NA NA − − NA NA NA NA NA NA − NA − − −
    Wound (40) − − 10.0/7.5 42.5/42.5 − − 2.5/5.0 0/7.5 0/0 15.0/5.0 2.5/20.0 2.5/22.5 − 7.5/0 − − −
    Respiratory (217) − − 16.1/6.9 44.2/30.4 − − 6.0/4.1 0/8.8 3.2/5.5 18.4/15.7 7.4/18.4 12.9/25.8 − 6.9/1.4 − − −
K. pneumoniae
    All (316) 2.8/0 4.8/6.3 0.3/0.9 1.6/1.3 4.1/3.5 0/0 0/0 1.9/2.5 0/0.6 0.6/2.8 2.2/7.3 1.3/5.1 − − 31.3/32.6 0/11.4 3.8/0.6
    Blood (139) 2.9/0 2.9/5.8 0/0.7 1.4/0.7 2.9/3.6 0/0 0/0 0.7/1.4 0/0 0.7/1.4 2.9/4.3 0.7/2.9 − − 38.8/26.6 0/11.5 1.4/0.7
    Urine (98) 0/0 2.0/7.1 1.0/1.0 1.0/2.0 8.2/1.0 0/0 0/0 4.1/3.1 0/1.0 1.0/5.1 2.0/12.2 2.0/8.2 − − 21.4/45.9 0/15.3 7.1/0
    Wound (13) NA NA NA NA NA NA NA NA NA NA NA NA − − NA NA NA
    Respiratory (66) 6.1/0 10.6/6.1 0/1.5 1.5/1.5 0/6.1 0/0 0/0 1.5/4.5 0/1.5 0/1.5 0/4.5 0/3.0 − − 28.8/22.7 0/4.5 3.0/0
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a

I, intermediate; R, resistant; NA, no isolates met criteria or there were insufficient numbers for analysis (n < 40); −, no defined breakpoints; A/C, amoxicillin-clavulanate; CFZ, cefazolin; CPM, cefepime; CTR, ceftriaxone; FOX, cefoxitin; ETP, ertapenem; MER, meropenem; PTZ, piperacillin-tazobactam; AMK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; LEV, levofloxacin; MXF, moxifloxacin; COL, colistin; FD, nitrofurantoin; TGC, tigecycline.

b

Indicated for use against urinary tract isolates only (CLSI M100-S19).

Antimicrobial resistance rates for the most common Gram-negative bacilli based on hospital ward location are listed in Table 6. With E. coli, antimicrobial resistance rates for penicillins, cephalosporins, fluoroquinolones, and aminoglycosides were highest in isolates obtained from ICUs. With P. aeruginosa (excluding the cystic fibrosis clinics), resistance rates were highest in ICU specimens for penicillins, cephalosporins, carbapenems, fluoroquinolones, and aminoglycosides.

TABLE 6.

Resistance rates for the most common Gram-negative bacilli isolated from CaNAdian hospitals, based on hospital locationa

Organism and location (n) % I/% R
A/C CFZ CPM CTR FOX ETP MER PTZ AMK GEN CIP LEV MXF COL FDb SXT TGC
E.coli
    All (1,132) 1.4/0.5 2.2/10.0 1.1/1.6 0.9/4.4 3.6/5.6 0/0 0/0 1.9/1.2 0.2/0.3 0.3/9.7 0.2/22.1 0.5/21.6 − − 1.9/1.1 0/27.7 0.2/0
    Clinic (159) 2.5/0 1.9/6.9 0.6/0.6 0/2.5 3.1/5.0 0/0 0/0 1.9/0.6 0/0 0.6/8.2 0/19.5 1.3/18.2 − − 1.3/1.3 0/25.8 0/0
    ER (453) 0.7/0.7 2.2/8.4 1.6/1.3 0.7/4.0 2.4/4.0 0/0 0/0 1.6/0.2 0.2/0.2 0/9.1 0.2/18.5 0.4/18.3 − − 2.0/0.4 0/27.1 0.2/0
    ICU (75) 5.3/0 4.0/20.0 1.3/2.7 4.0/8.0 2.7/10.7 0/0 0/0 2.7/4.0 0/0 1.3/13.3 0/28.0 1.3/26.7 − − 2.7/1.3 0/28.0 0/0
    Medical (375) 1.3/0.8 1.6/12.0 1.1/2.1 0.8/5.3 4.8/6.9 0/0 0/0 2.4/2.4 0.3/0.5 0.5/10.4 0.3/25.3 0.3/25.1 − − 1.6/1.6 0/30.1 0.3/0
    Surgical (70) 0/0 4.3/5.7 0/1.4 1.4/2.9 7.1/5.7 0/0 0/0 1.4/0 0/1.4 0/10.0 0/27.1 0/27.1 − − 4.3/1.4 0/22.9 0/0
P. aeruginosa
    All (373) − − 12.1/7.2 45.8/32.7 − − 4.0/5.6 0/8.0 2.7/3.5 16.6/12.3 5.6/19.0 11.3/24.1 − 7.2/0.8 − − −
    Clinic (88) − − 7.9/11.4 43.2/27.3 − − 5.7/1.1 0/10.2 4.5/9.1 14.8/25.0 7.9/17.0 12.5/20.4 − 6.8/2.3 − − −
    ER (54) − − 13.0/1.8 61.1/22.2 − − 1.8/3.7 0/1.8 3.7/0 20.4/7.4 3.7/16.7 7.4/18.5 − 3.7/0 − − −
    ICU (67) − − 13.4/6.0 44.8/35.8 − − 6.0/9.0 0/7.5 3.0/6.0 14.9/10.4 4.5/19.4 13.4/25.4 − 13.4/0 − − −
    Medical (131) − − 15.3/6.1 44.3/38.2 − − 2.3/5.3 0/9.9 1.5/0.8 16.8/6.1 6.9/19.1 11.4/25.9 − 6.9/0.8 − − −
    Surgical (33) − − NA NA − − NA NA NA NA NA NA − NA − − −
K. pneumoniae
    All (316) 2.8/0 4.8/6.3 0.3/0.9 1.6/1.3 4.1/3.5 0/0 0/0 1.9/2.5 0/0.6 0.6/2.8 2.2/7.3 1.3/5.1 − − 31.3/32.6 0/11.4 3.8/0.6
    Clinic (28) NA NA NA NA NA NA NA NA NA NA NA NA − − NA NA NA
    ER (80) 0/0 1.2/1.2 0/0 1.2/0 2.5/1.2 0/0 0/0 0/1.2 0/0 0/1.2 2.5/2.5 0/0 − − 41.2/25.0 0/8.7 0/0
    ICU (63) 9.5/0 6.3/9.5 0/1.6 3.2/1.6 0/4.8 0/0 0/0 0/6.3 0/1.6 0/3.2 0/3.2 0/3.2 − − 25.4/25.4 0/6.3 3.2/0
    Medical (115) 1.7/0 7.8/8.7 0.9/1.7 0.9/2.6 5.2/4.3 0/0 0/0 4.3/2.6 0/0.9 0.9/4.3 1.7/10.4 1.7/7.8 − − 29.6/37.4 0/15.6 6.1/0
    Surgical (30) NA NA NA NA NA NA NA NA NA NA NA NA − − NA NA NA
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a

I, intermediate; R, resistant; NA, no isolates met criteria or there were insufficient numbers for analysis (n < 40); −, no defined breakpoints; A/C, amoxicillin-clavulanate; CFZ, cefazolin; CPM, cefepime; CTR, ceftriaxone; FOX, cefoxitin; ETP, ertapenem; MER, meropenem; PTZ, piperacillin-tazobactam; AMK, amikacin; GEN, gentamicin; CIP, ciprofloxacin; LEV, levofloxacin; MXF, moxifloxacin; COL, colistin; FD, nitrofurantoin; TGC, tigecycline.

b

Indicated for use against urinary tract isolates only (CLSI M100-S19).

The ordinal logistic regression model showed that Gram-negative bacilli were resistant to more classes of antimicrobials when obtained from inpatients (P < 0.001) and men (P < 0.001). Similarly, Gram-negative isolates were more likely to be pan-susceptible when obtained from outpatients (P < 0.001) and women (P < 0.001).

MDR.

Multidrug resistance was assessed in Gram-negative organisms only, because no accepted definition exists for Gram-positive organisms (Table 7). Multidrug resistance for Gram-negative organisms was defined as resistance to ≥3 of the following: cefepime, piperacillin-tazobactam, meropenem, amikacin or gentamicin, and ciprofloxacin (20, 37). In general, the nominal regression analysis showed that Gram-negative bacilli were more likely to be MDR when the specimens were obtained from men (P = 0.008) and inpatients (P < 0.001). The MDR phenotype was most common in P. aeruginosa at 5.9%. An MDR phenotype occurred in 1.2% of E. coli, 0.9% of K. pneumoniae, 0% of E. cloacae, and 0% H. influenzae (Table 7). No statistically significant association could be made between rates of MDR E. coli or P. aeruginosa and hospital locations or specimen sources.

TABLE 7.

MDR phenotypes in Canadian hospitalsa

Organism No. of MDR isolates/total no. of isolates % of isolates that were MDR
E. coli 14/1,132 1.2
P. aeruginosa 22/373 5.9
K. pneumoniae 3/316 0.9
E. cloacae 0/114 0
H. influenzae 0/214 0
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a

Multidrug resistance for Gram-negative bacilli was defined as resistance to ≥3 of the following: cefepime, piperacillin-tazobactam, meropenem, amikacin or gentamicin, and ciprofloxacin.

DISCUSSION

The CANWARD study is the first national, prospective surveillance study assessing antimicrobial resistance in hospitals across Canada. In 2008, this national surveillance study involved 10 medical centers in major population centers in 7 of the 10 provinces in Canada. Each medical center collected clinically significant bacterial isolates from blood, respiratory, wound, and urinary specimens. Previous surveillance studies had documented that more than half of all bacterial isolates recovered from clinical specimens in hospitals were from the respiratory tract (7). Such conclusions cannot be drawn from the CANWARD 2008 study, because it was designed to collect isolates from a variety of specimen sources to assess antimicrobial resistance patterns, rather than assessing the prevalence of infectious diseases in Canadian hospitals. Christensen et al. recently reported that in the United States from 1998 to 2006, respiratory tract infections were the most common infectious diseases requiring hospitalization, followed by infections of the urinary tract, cellulitis, septicemia, and abdominal/rectal infections (7). Thus, the CANWARD 2008 study, which focused on bacterial isolates obtained from blood, the respiratory tract, the urinary tract, and wounds, is reflective of the most common infectious sites in hospitals. We report that the 10 most common isolates recovered from 78.8% of all clinical specimens in hospitals across Canada were E. coli, MSSA, S. pneumoniae, P. aeruginosa, K. pneumoniae, coagulase-negative staphylococci/S. epidermidis, MRSA, H. influenzae, Enterococcus spp., and E. cloacae (Table 1). Our data concur with previous reports that Gram-positive cocci, including MSSA, S. pneumoniae, MRSA, and Enterococcus spp., are the most common Gram-positive isolates recovered from clinical specimens in North American hospitals (13, 37). In addition, our data support that E. coli, P. aeruginosa, K. pneumoniae, and E. cloacae are the most common Gram-negative bacilli causing infections in North American hospitals (20, 37).

In CANWARD 2008, MSSA and MRSA (in all regions studied) were important isolates recovered from clinical specimens, including bacteremia, the respiratory tract, and wounds. Twenty-seven percent of all S. aureus isolates were MRSA (geographic variability, 19.3 to 31.6%), which is not different from the 26.0% we reported from CANWARD 2007 (39). Surprisingly, 27.6% of all MRSA isolates in Canadian hospitals were CA-MRSA, as determined genotypically. In CANWARD 2007, we reported the rate of CA-MRSA in Canadian hospitals to be 19.5%, while in a similar study assessing antimicrobial resistance in Canadian ICUs that was conducted in 2005-2006, we reported that 9.1% of all MRSA were CA-MRSA (24, 38, 39). Thus, it is clear that CA-MRSA genotypes are rapidly spreading beyond the community setting and throughout Canadian hospitals (14). CMRSA-10/USA300 continues to be the predominant CA-MRSA genotype in Canadian hospitals, as previously reported (37-39). The most common HA-MRSA genotypes in Canadian hospitals were CMRSA-2/USA100/800 (81.9%) and CMRSA-6 or CMRSA-3 (12.8%), as has also been previously documented (8, 23, 37). The resistance rates among MRSA were high (>50%) with fluoroquinolones and macrolides (such as clarithromycin), as well as clindamycin, but lower with SXT (10.3%). These resistance rates are consistent with previous reports (23, 37) and suggest that SXT remains a reasonable empirical treatment for mild to moderate infections (e.g., skin and soft tissue infections) caused by CA-MRSA or HA-MRSA. Eight of 272 (2.9%) MRSA isolates demonstrated vancomycin MICs of 2 μg/ml, which is an increase from CANWARD 2007, for which we documented a rate of 1.0% (38, 39). Although we did not assess the prevalence of hetero-resistant vancomycin-intermediate S. aureus (hVISA), a recent Canadian study reported that 8.1% (22 of 271) of MRSA isolates with a vancomycin MIC of 2 μg/ml collected across Canada from 1995 to 2006 were hVISA based on population analysis profiling (1). Similarly, a recent analysis from Detroit identified 8.3% (of 917 strains assessed from 2003 to 2007) of MRSA isolates as hVISA (31).

We report that only 3.1% of all enterococci were VRE in our study, of which all were E. faecium and displayed the vanA genotype. In CANWARD 2007, we reported 1.8% VRE with the majority (62.5%) having the vanA genotype (39). This study confirms that E. faecium carrying vanA continues to be the predominant VRE genotype in North America (12, 36, 38). The low level of VRE across Canada has been previously documented and highlights the lack of spread of VRE across the country (36, 38). The continued low level of VRE in Canadian hospitals likely reflects the use of active surveillance programs as well as infection control programs (e.g., aggressive hand hygiene) and antimicrobial stewardship programs, which have been shown to prevent VRE and MRSA infections (11, 16, 18, 32). None of the enterococci displayed resistance to tigecycline or daptomycin.

The CANWARD 2008 study found that 4.9% of E. coli isolates were ESBL producers (an increase from 3.4% in CANWARD 2007) and that all areas of the hospital were affected. The observations that ESBL-producing E. coli were identified in all geographic regions of the country and 76.4% of the isolates displayed an MDR phenotype alert researchers and clinicians that MDR ESBL-producing E. coli isolates are increasing in Canadian hospitals. This study demonstrated that the CTX-M genotype (blaCTX-M-15 and blaCTX-M-14) was the predominant genotype in Canadian hospitals. Other studies assessing ESBL-producing E. coli have shown that the CTX-M genotype is spreading rapidly in both community and hospital settings (3, 5, 19, 22, 26-28). Recently, Peirano et al. reported on ESBL-producing E. coli from 11 Canadian medical units based on phenotypic and genotypic methods to characterize the isolates. CTX-M-15 was the predominant genotype produced (71%; 148/209), while 8% (17/209) produced CTX-M-14 (26). ESBL-producing E. coli most commonly belonged to clonal complex ST131 (46%; 96/209) (26). CANWARD 2008 highlights the rapid spread of CTX-M-15 E. coli and MDR CTX-M-15 in Canadian hospitals. This MDR phenotype may be spreading rapidly in part due to the continued extensive use of broad-spectrum cephalosporins and fluoroquinolones. Hsu et al. recently reported a correlation between the use of broad-spectrum cephalosporins and fluoroquinolones and antimicrobial-resistant E. coli (17).

This study found associations between increasing age and inpatient status and resistance in Gram-positive cocci. For Gram-negative bacilli, resistance was more likely to occur in isolates obtained from inpatients and men. These data support the current literature, which indicates that antimicrobial resistance generally increases with increasing age and among inpatients (4, 34). Especially among urinary tract isolates of E. coli, it has been established that resistance is higher in men than in women and increases with age (4). With E. coli and P. aeruginosa (excluding the cystic fibrosis clinics), antimicrobial resistance rates were highest in isolates obtained from the ICU. This finding is consistent with previous studies where higher resistance rates in the ICU were reported for Gram-negative bacilli (20, 29, 37).

The lowest rates of resistance for Gram-negative bacilli occurred with amikacin, amoxicillin-clavulanate, cefepime, doripenem, ertapenem (except P. aeruginosa), meropenem, and piperacillin-tazobactam, which is consistent with previous reports (20, 29, 37). With P. aeruginosa, carbapenem activity was observed in the following order: doripenem > meropenem (imipenem was not tested). The low level of resistance in Gram-negative bacilli with amikacin likely reflects the low usage of aminoglycosides in favor of the fluoroquinolones in Canada and the United States over the past decade. In contrast, fluoroquinolone resistance was high with E. coli (21.6 to 22.1%) and P. aeruginosa (19.0 to 24.1%), which is consistent with other reports (20, 29, 37) and reflects extensive fluoroquinolone usage (17). A recent report documented increasing prevalence of MDR Gram-negative bacilli in ICUs in the United States (20). Our definition of multidrug resistance for Gram-negative bacilli (resistance to ≥3 of the following: cefepime, piperacillin-tazobactam, meropenem, amikacin or gentamicin, and ciprofloxacin) was slightly more restrictive than that used in the U.S. study; thus, it was not surprising that our MDR rate of 5.9% with P. aeruginosa was somewhat lower than that previously reported in the United States of 9.3% (20). MDR rates in Gram-negative bacilli in Canadian hospitals (E. coli, 1.2%; E. cloacae, 0%; K. pneumoniae, 0.9%) are lower than those in U.S. institutions (E. coli, 2.0%; E. cloacae, 5.9%; K. pneumoniae, 13.3%) (20). The explanation for the lower MDR rates with Enterobacteriaceae (E. coli, E. cloacae, and K. pneumoniae) in Canada is unclear but may include the fact that Canada has a lower prevalence of ESBL-producing Enterobacteriaceae or the fact that Canada aggressively promotes active surveillance programs, infection control programs (e.g., diligent hand hygiene), and antimicrobial stewardship programs (2, 3, 5, 11, 16, 18, 32). MDR ESBL-producing E. coli isolates were all susceptible to the carbapenems doripenem, ertapenem, and meropenem, as well as to tigecycline.

The limitations of the CANWARD study include the fact that we cannot be certain that all clinical specimens represent active infection. As in our previous CANWARD 2007 and CAN-ICU studies (37-39), we asked centers to provide potentially pathogenic isolates from “clinically significant” specimens from patients with a presumed or proven infectious disease. Although it is possible that not all of the organisms were isolated from actual infections in patients, we believe that the vast majority of the isolates would have been collected from clinically significant samples, as we excluded all surveillance swabs, duplicate swabs, eye, ear, nose, and throat swabs, and genital cultures. Another limitation of this study is that we did not have admission date data for each patient/clinical specimen, and thus we were not able to provide a completely accurate description of community versus nosocomial onset. The CANWARD study assessed antimicrobial resistance rates in tertiary care medical centers across Canada and thus may depict inflated resistance rates compared to smaller, community practice hospitals. In this study, CA-MRSA and HA-MRSA were defined genotypically, not epidemiologically, and it has been shown epidemiologically that CA-MRSA genotypes can be associated with HA infections and that HA-MRSA can be associated with CA infections (8). Susceptibility testing was not performed (nor fully reported) for all antimicrobial agents due to a lack of space on the susceptibility panels utilized (or in data tables). It is recognized that data on antimicrobials such as ceftazidime, imipenem, tobramycin, and others would be beneficial, as different hospital formularies stock these and other antimicrobials not tested in this study. Finally, performing statistical analyses by collapsing various Gram-positive cocci (e.g., MSSA, MRSA, and VRE) or various Gram-negative bacilli (e.g., Enterobacteriaceae and nonfermenters) together to assess risk factors for resistance may not be appropriate. The analysis was performed to assess general risk factor trends.

In conclusion, E. coli, S. aureus (MSSA and MRSA), P. aeruginosa, S. pneumoniae, K. pneumoniae, H. influenzae, and Enterococcus spp. are the most common isolates recovered from clinical specimens in Canadian hospitals. The prevalence of MRSA was 27.0% (of which, genotypically, 27.6% was CA-MRSA), the prevalence of VRE was 3.1%, and ESBL-producing E. coli occurred in 4.9% of isolates. An MDR phenotype is common with P. aeruginosa in Canadian hospitals.

Acknowledgments

Funding for the CANWARD 2008 study was provided in part by the University of Manitoba Health Sciences Centre in Winnipeg, the National Microbiology Laboratory-Health Canada, Abbott, Astellas, Bayer, Janssen Ortho Inc., Merck, Oryx, Pfizer Canada, TaiGen, Targanta, and Wyeth Inc.

We thank the investigators and laboratory site staff at each medical center that participated in the CANWARD 2008 study: Vancouver Hospital, Vancouver, BC (D. Roscoe); University of Alberta Hospitals, Edmonton, AB (R. Rennie); Royal University Hospital, Saskatoon, SK (J. Blondeau); Health Sciences Centre, Winnipeg, MB (D. Hoban/G. Zhanel); Mount Sinai Hospital, Toronto, ON (S. Poutanen); Children's Hospital of Eastern Ontario, Ottawa, ON (F. Chan); London Health Sciences Centre, London, ON (Z. Hussain); Hopital Maisonneuve-Rosemont, Montreal, QC (M. Laverdiere); Montreal General Hospital, Montreal, QC (V. Loo); and QEII Health Sciences Centre, Halifax, NS (K. Forward/R. Davidson).

We give special thanks to Nancy Laing, Barb Weshnoweski, Ravi Vashisht, Lisa Bittner, and Leanne Scharikow for technological assistance. We thank M. Tarka for expert secretarial assistance.

Footnotes

▿

Published ahead of print on 30 August 2010.

REFERENCES

  • 1.Adam, H. J., L. Louie, C. Watt, D. Gravel, E. Bryce, M. Loeb, A. Matlow, A. McGeer, M. R. Mulvey, A. E. Simor, and the Canadian Nosocomial Infection Surveillance Program. 2010. Detection and characterization of heterogenous vancomycin-intermediate Staphylococcus aureus isolates in Canada: results from the Canadian Nosocomial Infection Surveillance Program, 1995-2006. Antimicrob. Agents Chemother. 54:945-949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Baudry, P. J., K. Nichol, M. DeCorby, L. Mataseje, M. Mulvey, D. J. Hoban, and G. G. Zhanel. 2008. Comparison of antimicrobial resistance profiles among extended-spectrum β-lactamase-producing and acquired AmpC β-lactamase-producing Escherichia coli isolates from Canadian intensive care units. Antimicrob. Agents Chemother. 52:1846-1849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Baudry, P. J., M. McCracken, P. Lagacé-Wiens, M. Mulvey, G. G. Zhanel, and D. J. Hoban. 2009. Prevalence and characterization of extended-spectrum β-lactamase-producing Enterobacteriaceae isolated in Canadian hospitals: results from CANWARD 2007. Can. J. Infect. Dis. Med. Microbiol. 20(Suppl. A):43-48. [Google Scholar]
  • 4.Blaettler, L., D. Mertz, R. Frei, L. Elzi, A. F. Widmer, M. Battegay, and U. Fluckiger. 2009. Secular trend and risk factors for antimicrobial resistnace in Escherichia coli isolates in Switzerland 1997-2007. Infection 37:534-539. [DOI] [PubMed] [Google Scholar]
  • 5.Castanheira, M., R. E. Mendes, P. R. Rhomberg, and R. N. Jones. 2008. Rapid emergence of blaCTX-M among Enterobacteriaceae in US medical centers: molecular evaluation from the MYSTIC program (2007). Microb. Drug Resist. 14:211-216. [DOI] [PubMed] [Google Scholar]
  • 6.Chambers, H. F. 2005. Community-associated MRSA-resistance and virulence converge. N. Engl. J. Med. 352:1485-1487. [DOI] [PubMed] [Google Scholar]
  • 7.Christensen, K. L. Y., R. C. Holman, C. A. Steiner, J. J. Sejvar, B. J. Stoll, and L. B. Schonberger. 2009. Infectious disease hospitalizations in the United States. Clin. Infect. Dis. 49:1025-1035. [DOI] [PubMed] [Google Scholar]
  • 8.Christianson, S., G. R. Golding, J. Campbell, the Canadian Nosocomial Infection Surveillance Program, and M. R. Mulvey. 2007. Comparative genomics of Canadian epidemic lineages of methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol. 45:1904-1911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Clinical and Laboratory Standards Institute. 2009. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; 8th edition, M07-A8. Clinical and Laboratory Standards Institute, Wayne, PA.
  • 10.Clinical and Laboratory Standards Institute. 2009. Performance standards for antimicrobial susceptibility testing: 19th informational supplement document M100-S19. Clinical and Laboratory Standards Institute, Wayne, PA.
  • 11.Dellit, T. H., R. C. Owens, J. E. McGowan, D. N. Gerding, R. A. Weinstein, J. P. Burke, W. C. Huskins, D. L. Paterson, N. O. Fishman, C. F. Carpenter, P. J. Brennan, M. Billeter, T. M. Hooton, the Infectious Diseases Society of America, and the Society for Healthcare Epidemiology of America. 2007. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin. Infect. Dis. 44:159-177. [DOI] [PubMed] [Google Scholar]
  • 12.Deshpande, L. M., T. R. Fritsche, G. J. Moet, D. J. Biedenbach, and R. N. Jones. 2007. Antimicrobial resistance and molecular epidemiology of vancomycin-resistant enterococci from North America and Europe: a report from the SENTRY antimicrobial surveillance program. Diagn. Microbiol. Infect. Dis. 58:163-170. [DOI] [PubMed] [Google Scholar]
  • 13.Fridkin, S. K., J. E. Edwards, F. C. Tenover, R. P. Gaynes, J. E. McGowan, Jr., the Intensive Care Antimicrobial Resistance Epidemiology (ICARE) Project, and the National Nosocomial Infections Surveillance (NNIS) system hospitals. 2001. Antimicrobial resistance prevalence rates in hospital antibiograms reflect prevalence rates among pathogens associated with hospital-acquired infections. Clin. Infect. Dis. 33:324-330. [DOI] [PubMed] [Google Scholar]
  • 14.Gilbert, M., J. MacDonald, D. Gregson, J. Siushansian, K. Zhang, S. Elsayed, K. Laupland, T. Louie, M. Mulvey, J. Gillespie, D. Nielsen, V. Wheeler, M. Louie, A. Honish, G. Keays, and J. Conly. 2006. Outbreak in Alberta of community-acquired (USA300) methicillin-resistant Staphylococcus aureus in people with a history of drug use, homelessness and incarceration. Can. Med. Assoc. J. 175:149-154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Golding, G. R, J. L. Campbell, D. J. Spreitzer, J. Veyhl, K. Surynicz, A. Simor, M. R. Mulvey, and the Canadian Nosocomial Infection Surveillance Program. 2008. A preliminary guideline for the assignment of methicillin-resistant Staphylococcus aureus to a Canadian pulsed-field gel electrophoresis epidemic type using spa typing. Can. J. Infect. Dis. Med. Microbiol. 19:273-281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Grayson, M. L., L. J. Jarvie, R. Martin, M. E. Jodoin, C. McMullan, R. H. Gregory, K. Bellis, K. Cunnington, F. L. Wilson, D. Quin, A. M. Kelly, and the Hand Hygiene Study Group and Hand Hygiene Statewide Roll-Out Group, Victorian Quality Council. 2008. Significant reductions in methicillin-resistant Staphylococcus aureus bacteremia and clinical isolates associated with multisite hand hygiene culture change program and subsequent successful statewide roll-out. Med. J. Aust. 188:633-640. [DOI] [PubMed] [Google Scholar]
  • 17.Hsu, L. Y., Y. T. Tam, A. Kwa, D. A. Fisher, and T. H. Koh. 2010. Surveillance and correlation of antibiotic prescription and resistance of Gram-negative bacteria in Singapore hospitals. Antimicrob. Agents Chemother. 54:1173-1178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Huang, S. S., D. S. Yokoe, V. L. Hinrichsen, L. S. Spurchise, R. Datta, I. Miroshnik, and R. Platt. 2006. Impact of routine intensive care unit surveillance cultures and resultant barrier precautions on hospital-wide methicillin-resistant Staphylococcus aureus bacteremia. Clin. Infect. Dis. 43:971-978. [DOI] [PubMed] [Google Scholar]
  • 19.Lewis, J. S., M. Herraera, B. Wickes, J. E. Patterson, and J. H. Jorgensen. 2007. First report of the emergence of CTX-M-type extended-spectrum β-lactamases (ESBL) as the predominant ESBL isolated in a U.S. health care system. Antimicrob. Agents Chemother. 51:4015-4021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Lockhart, S. R., M. A. Abramson, S. E. Beekman, G. Gallagher, S. R. Riedel, D. J. Diekma, J. P. Quinn, and G. V. Doern. 2007. Antimicrobial resistance among Gram-negative bacilli as causes of infections in intensive care unit patients in the United States between 1993 and 2004. J. Clin. Microbiol. 45:3352-3359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Lynch, J. P., and G. G. Zhanel. 2009. Streptococcus pneumoniae: does antimicrobial resistance matter? Semin. Respir. Crit. Care Med. 30:210-238. [DOI] [PubMed] [Google Scholar]
  • 22.Mulvey, M. R., E. Bryce, D. Boyd, M. Ofner-Agostini, S. Christianson, A. E. Simor, S. Paton, and the Canadian Hospital Epidemiology Committee of the Canadian Nosocomial Infection Surveillance Program, Health Canada. 2004. Ampler class A extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. in Canadian hospitals. Antimicrob. Agents Chemother. 48:1204-1214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Mulvey, M. R., L. MacDougall, B. Cholin, G. Horsman, M. Fidyk, S. Woods, and the Saskatchewan CA-MRSA Study Group. 2005. Community-associated methicillin-resistant Staphylococcus aureus, Canada. Emerg. Infect. Dis. 11:844-850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Nichol, K. A., M. R. DeCorby, K. Thompson, M. Mulvey, J. A. Karlowsky, D. J. Hoban, and G. G. Zhanel. 2009. Comparison of community-associated and hospital-associated methicillin-resistant Staphylococcus aureus in Canada: results from CANWARD 2007. Can. J. Infect. Dis. Med. Microbiol. 20(Suppl. A):31-36. [Google Scholar]
  • 25.Oliveira, D. C., and H. de Lencastre. 2002. Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 46:2155-2161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Peirano, G., D. Richardson, J. Nigrin, A. McGeer, V. Loo, B. Toye, M. Alfa Pienaar, C. P. Kibsey, and J. D. Pitout. 2010. The high prevalence of ST131 producing CTX-M-15 and CTX-M-14 among extended extended-spectrum beta-lactamase-producing Escherichia coli across Canada. Antimicrob. Agents Chemother. 54:1327-1330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Pitout, J. D. D., D. L. Church, D. B. Gregson, B. L. Chow, M. McCracken, M. Mulvey, and K. B. Laupland. 2007. Molecular epidemiology of CTX-M-producing Escherichia coli in the Calgary Health Region: emergence of CTX-M-15-producing isolates. Antimicrob. Agents Chemother. 51:1281-1286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Pitout, J. D., D. B. Gregson, L. Campbell, and K. B. Laupland. 2009. Molecular characteristics of extended-spectrum beta-lactamase-producing Escherichia coli isolates causing bacteremia in the Calgary Health Region from 2000 to 2007: emergence of clone ST131 as a cause of community-acquired infections. Antimicrob. Agents Chemother. 53:2846-2851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Rhomberg, P. P., and R. N. Jones. 2009. Summary trends for the meropenem yearly susceptibility test information collection program: a 10 year experience in the United States (1999-2008). Diagn. Microbiol. Infect. Dis. 65:414-426. [DOI] [PubMed] [Google Scholar]
  • 30.Rubinstein, E., and G. G. Zhanel. 2007. Anti-infectives research and development problems challenges and solutions: the clinical practitioner perspective. Lancet Infect. Dis. 7:69-70. [DOI] [PubMed] [Google Scholar]
  • 31.Rybak, M. J., S. N. Leonard, K. L. Rossi, C. M. Cheung, H. S. Sader, and R. N. Jones. 2008. Characterization of vancomycin-heteroresistant Staphylococcus aureus from the metropolitan area of Detroit, Michigan, over a 22-year period (1986 to 2007). J. Clin. Microbiol. 46:2950-2954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Shadel, B. N., L. A. Puzniak, K. N. Gillespie, S. J. Lawrence, M. Kollef, and L. M. Mundy. 2006. Surveillance for vancomycin-resistant enterococci: type, rates costs and implications. Infect. Control Hosp. Epidemiol. 27:1068-1075. [DOI] [PubMed] [Google Scholar]
  • 33.Tenover, F. C., R. D. Arbeit, R. V. Goering, P. A. Mickelson, B. E. Murray, D. H. Persing, et al. 1995. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J. Clin. Microbiol. 33:2233-2239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Weber, S. G., R. R. Miller, E. N. Perencevich, J. Polentino, D. Meltzer, D. Pitrak, J. C. McGregor, G. A. Sachs, A. D. Harris, and J. P. Furuno. 2009. Prevalence of antimicrobial-resistant bacteria isolated from older versus younger hospitalized adults: results of a two-center study. J. Antimicrob. Chemother. 64:1291-1298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Whitney, C. G., M. M. Farley, and J. Hadler. 2000. Increasing prevalence of multi-drug resistant Streptococcus pneumoniae in the United States. N. Engl. J. Med. 343:1817-1824. [DOI] [PubMed] [Google Scholar]
  • 36.Zhanel, G. G., N. M. Laing, K. A. Nichol, L. P. Palatnick, A. Noreddin, T. Hisanaga, J. L. Johnson, the NAVRESS Group, and D. J. Hoban. 2003. Antibiotic activity against urinary tract infection (UTI) isolates of vancomycin-resistant enterococci (VRE): results from the 2002 North America Vancomycin Resistant Enterococci Susceptibility Study (NAVRESS). J. Antimicrob. Chemother. 52:382-388. [DOI] [PubMed] [Google Scholar]
  • 37.Zhanel, G. G., M. DeCorby, N. Laing, B. Weshnoweski, R. Vashisht, F. Tailor, K. A. Nichol, A. Wierzbowski, P. Baudry, J. Karlowsky, P. Lagace-Wiens, A. Walkty, M. McCracken, M. Mulvey, J. Johnson, the Canadian Antimicrobial Resistance Alliance (CARA), and D. J. Hoban. 2008. Antimicrobial-resistant pathogens in intensive care units in Canada: results of the Canadian National Intensive Care Unit (CAN-ICU) Study, 2005/2006. Antimicrob. Agents. Chemother. 52:1430-1437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Zhanel, G. G., M. DeCorby, K. A. Nichol, P. Baudry, J. A. Karlowsky, M. McCracken, M. R. Mulvey, the Canadian Antimicrobial Resistance Alliance (CARA), and D. J. Hoban. 2008. Characterization of MRSA, VRE and ESBL producing E. coli in intensive care units in Canada: results of the Canadian National Intensive Care Unit (CAN-ICU) Study, 2005/2006. Can. J. Infect. Dis. Med. Microbiol. 19:243-249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Zhanel, G. G., J. A. Karlowsky, M. DeCorby, K. A. Nichol, P. Baudry, A. Wierzbowski, P. J. Baudry, P. Lagace-Wiens, A. Walkty, F. Schweizer, H. Adam, M. McCracken, M. R. Mulvey, the Canadian Antimicrobial Resistance Alliance (CARA), and D. J. Hoban. 2009. Prevalence of antimicrobial-resistant pathogens in Canadian hospitals: results of the Canadian Ward Surveillance Study (CANWARD 2007). Can. J. Infect. Dis. Med. Microbiol. 20(Suppl. A):9-19.20190888 [Google Scholar]

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