Antimicrobial resistance in urinary tract pathogens in Canada from 2007 to 2009: CANWARD surveillance study.

From January 2007 to December 2009, an annual Canadian national surveillance study (CANWARD) tested 2,943 urinary culture pathogens for antimicrobial susceptibilities according to Clinical and Laboratory Standards Institute guidelines. The most frequently isolated urinary pathogens were as follows (number of isolates, percentage of all isolates): Escherichia coli (1,581, 54%), enterococci (410, 14%), Klebsiella pneumoniae (274, 9%), Proteus mirabilis (122, 4%), Pseudomonas aeruginosa (100, 3%), and Staphylococcus aureus (80, 3%). The rates of susceptibility to trimethoprim-sulfamethoxazole (SXT) were 78, 86, 84, and 93%, respectively, for E. coli, K. pneumoniae, P. mirabilis, and S. aureus. The rates of susceptibility to nitrofurantoin were 96, 97, 33, and 100%, respectively, for E. coli, enterococci, K. pneumoniae, and S. aureus. The rates of susceptibility to ciprofloxacin were 81, 40, 86, 81, 66, and 41%, respectively, for E. coli, enterococci, K. pneumoniae, P. mirabilis, P. aeruginosa, and S. aureus. Statistical analysis of resistance rates (resistant plus intermediate isolates) by year for E. coli over the 3-year study period demonstrated that increased resistance rates occurred only for amoxicillin-clavulanate (from 1.8 to 6.6%; P < 0.001) and for SXT (from 18.6 to 24.3%; P = 0.02). For isolates of E. coli, in a multivariate logistic regression model, hospital location was independently associated with resistance to ciprofloxacin (P = 0.026) with higher rates of resistance observed in inpatient areas (medical, surgical, and intensive care unit wards). Increased age was also associated with resistance to ciprofloxacin (P < 0.001) and with resistance to two or more commonly prescribed oral agents (amoxicillin-clavulanate, ciprofloxacin, nitrofurantoin, and SXT) (P = 0.005). We conclude that frequently prescribed empirical agents for urinary tract infections, such as SXT and ciprofloxacin, demonstrate lowered in vitro susceptibilities when tested against recent clinical isolates.

In vitro activity of ceftaroline against gram-positive and gram-negative pathogens isolated from patients in Canadian hospitals in 2009.

The in vitro activities of ceftaroline and comparative agents were determined for a collection of the most frequently isolated bacterial pathogens from hospital-associated patients across Canada in 2009 as part of the ongoing CANWARD surveillance study. In total, 4,546 isolates from 15 sentinel Canadian hospital laboratories were tested using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Compared with other cephalosporins, including ceftobiprole, cefepime, and ceftriaxone, ceftaroline exhibited the greatest potency against methicillin-susceptible Staphylococcus aureus (MSSA), with a MIC90 of 0.25 µg/ml. Ceftaroline also demonstrated greater potency than ceftobiprole against community-associated methicillin-resistant S. aureus (MRSA) (MIC90, 0.5 µg/ml) and health care-associated MRSA (MIC90, 1 µg/ml) and was at least 4-fold more active than other cephalosporins against Staphylococcus epidermidis; all isolates of MSSA and MRSA tested were susceptible to ceftaroline (MIC, ≤1 µg/ml). Against streptococci, including Streptococcus pneumoniae, ceftaroline MICs (MIC90, ≤0.03 µg/ml) were comparable to those of ceftobiprole; however, against penicillin-nonsusceptible, macrolide-nonsusceptible, and multidrug-nonsusceptible isolates of S. pneumoniae, ceftaroline demonstrated 2- to 4-fold and 4- to 16-fold more potent activities than those of ceftobiprole and ceftriaxone, respectively. All isolates of S. pneumoniae tested were susceptible to ceftaroline (MIC, ≤0.25 µg/ml). Among Gram-negative isolates, ceftaroline demonstrated potent activity (MIC90, ≤0.5 µg/ml) against Escherichia coli (92.2% of isolates were susceptible), Klebsiella pneumoniae (94.1% of isolates were susceptible), Proteus mirabilis (97.7% of isolates were susceptible), and Haemophilus influenzae (100% of isolates were susceptible). Ceftaroline demonstrated less potent activity (MIC90, ≥4 µg/ml) against Enterobacter spp., Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella oxytoca, Serratia marcescens, and Stenotrophomonas maltophilia. Overall, ceftaroline demonstrated potent in vitro activity against a recent collection of the most frequently encountered Gram-positive and Gram-negative isolates from patients attending hospitals across Canada in 2009.

Antimicrobial susceptibility of 15,644 pathogens from Canadian hospitals: results of the CANWARD 2007-2009 study.

The CANWARD study (Canadian Ward Surveillance Study) assessed the antimicrobial susceptibility of a variety of available agents against 15 644 pathogens isolated from patients in Canadian hospitals between 2007 and 2009. The most active (based on MIC data) agents against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci were daptomycin, linezolid, tigecycline, and vancomycin (MRSA only) with MIC(90)'s (µg/mL) of 0.25 and 2, 2 and 2, 0.5 and 0.12, and 1, respectively. The most active agents against extended-spectrum ß-lactamase-producing Escherichia coli were colistin (polymyxin E), doripenem, ertapenem, meropenem, and tigecycline with MIC(90)'s (µg/mL) of 1, ≤ 0.12, 0.25, ≤ 0.12, and 1, respectively. The most active agents against Pseudomonas aeruginosa were amikacin, cefepime, ceftazidime, colistin, doripenem, meropenem, and piperacillin-tazobactam with MIC(90)'s (µg/mL) of 32, 16, 32, 2, 4, 8, and 64, respectively. Overall, the most active agents versus Gram-positive cocci from Canadian hospitals were vancomycin, linezolid, daptomycin, and tigecycline and versus Gram-negative bacilli were amikacin, cefepime, doripenem, ertapenem (excluding Pseudomonas aeruginosa), meropenem, piperacillin-tazobactam, and tigecycline (excluding Pseudomonas aeruginosa).

Prevalence of antimicrobial resistant pathogens from blood cultures from Canadian hospitals: results of the CANWARD 2007-2009 study.

This study assessed the epidemiology and antimicrobial resistance of pathogens associated with bloodstream infections in Canadian hospitals between 2007 and 2009. Tertiary-care medical centers representing 8 of 10 Canadian provinces submitted bloodstream infection pathogens from patients attending hospital clinics, emergency rooms, medical/surgical wards, and intensive care units. Over 8,000 blood culture pathogens were collected. The 10 most common pathogens (representing 80.9% of all isolates) were Escherichia coli (1856 [22.6%]), Staphylococcus aureus (1457 [17.7%] including 1101 methicillin-susceptible Staphylococcus aureus and 356 methicillin-resistant Staphylococcus aureus), coagulase-negative staphylococci (907 [11.0%]), Klebsiella pneumoniae (600 [7.3%]), Streptococcus pneumoniae (470 [5.7%]), Enterococcus faecalis (360 [4.4%]), Pseudomonas aeruginosa (333 [4.0%]), viridans group streptococci (321 [3.9%]), Enterobacter cloacae (193 [2.3%]), and Streptococcus pyogenes (159 [1.9%]). The most active agents against Gram-negative bacilli were carbapenems (e.g., meropenem and ertapenem) and piperacillin-tazobactam, while for Gram-positive cocci, they were vancomycin, linezolid, and daptomycin.

Analysis of 3789 in- and outpatient Escherichia coli isolates from across Canada--results of the CANWARD 2007-2009 study.

Escherichia coli was the most commonly isolated pathogen in the Canadian Ward Surveillance Study 2007-2009 (3789 isolates). Susceptibility to cefazolin (34.1%), trimethoprim-sulfamethoxazole (73.8%), ciprofloxacin (78.4%), and levofloxacin (78.8%) was lowest. Susceptibility was above 90% for meropenem (100%), tigecycline (99.9%), piperacillin-tazobactam (97.6%), nitrofurantoin (96.9%), ceftazidime (95.6%), amoxicillin-clavulanate (94.9%), ceftriaxone (94.1%), cefoxitin (92.3%), and gentamicin (90.8%). Over the study period, there was a significant reduction in susceptibility to amoxicillin-clavulanate and trimethoprim-sulfamethoxazole for urinary tract isolates. Inpatient status was associated with greater resistance to nearly all antimicrobials including greater multidrug resistance (MDR). Increasing age was associated with resistance to fluoroquinolones, ceftriaxone, piperacillin-tazobactam, and MDR. Female gender was associated with susceptibility to fluoroquinolones and nitrofurantoin. In conclusion, greater antimicrobial resistance and MDR in E. coli were observed in inpatients, males, and with increasing age. The deterioration of susceptibility to trimethoprim-sulfamethoxazole continues with the greatest reduction in urinary isolates. Significant regional differences in resistance rates were apparent.

Prevalence of antimicrobial-resistant pathogens in Canadian hospitals: results of the Canadian Ward Surveillance Study (CANWARD 2008).

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 ß-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.

Mechanisms of resistance and mobility among multidrug-resistant CTX-M-producing Escherichia coli from Canadian intensive care units: the 1st report of QepA in North America.

We studied the molecular mechanisms of resistance and mobility of 18 multidrug-resistant CTX-M-producing Escherichia coli isolates isolated from patients in Canadian intensive care units. Fluoroquinolone-resistant isolates (83.3%) had mutations in gyrA and parC. Plasmid-mediated quinolone resistance genes qnr (A, B, and S), qepA, and aac(6')-Ib-cr were detected in 0%, 5.6%, and 44.4%, respectively. Sulfamethoxazole/trimethoprim-resistant isolates (61.1%) carried a dfr gene, and 10 (90.9%) of the 11 carried 1 or more sul genes. Gentamicin-resistant isolates (27.8%) carried the aac(3')-II gene, and doxycycline-resistant isolates (33.3%) carried 1 or more tet efflux genes. Both genetically related and unrelated groups of E. coli harboring extended-spectrum beta-lactamases were observed. The bla(CTX-M) genes were primarily located on diverse IncF plasmids of multiple replicon types downstream of the ISEcp1 element. The spread of the bla(CTX-M) genes among E. coli in Canada occurs through a diversity of different mechanisms and does not correspond to a single CTX-M determinant, or a single clone, or a single plasmid but rather through the combination of clonal spread of virulent strains and acquisition of diverse CTX-M-bearing plasmids. We report the 1st qepA-producing E. coli in North America.

Comparison of antimicrobial resistance profiles among extended-spectrum-beta-lactamase-producing and acquired AmpC beta-lactamase-producing Escherichia coli isolates from Canadian intensive care units.

Resistance profiles were compared among 18 extended-spectrum-beta-lactamase-producing (ESBL) and 27 acquired AmpC beta-lactamase-producing Escherichia coli isolates collected from Canadian intensive care units from 2005 to 2006. ESBL-producing E. coli isolates were more likely to be gentamicin resistant (P < 0.03), fluoroquinolone resistant (P < 0.0001), and multidrug resistant (P < 0.0001) than AmpC-producing E. coli isolates.

Antimicrobial susceptibility of Pseudomonas aeruginosa isolates obtained from patients in Canadian intensive care units as part of the Canadian National Intensive Care Unit study.

The antimicrobial susceptibility profile of 419 clinical isolates of Pseudomonas aeruginosa obtained from intensive care unit patients was determined. Amikacin and piperacillin/tazobactam were the most active antimicrobials evaluated. Fifty isolates (11.9%) were resistant to antimicrobials from > or =3 classes. Ninety-six percent of multidrug-resistant (MDR) isolates remained fully susceptible to colistin (polymyxin E).

Differences in antimicrobial susceptibility in Escherichia coli from Canadian intensive care units based on regional and demographic variables.

OBJECTIVES: Escherichia coli resistance to antimicrobials varies according to many factors. E coli isolates from Canadian intensive care units (ICUs) were studied to determine the distribution and demographics associated with antimicrobial resistance in this population. METHODS: The Canadian National Intensive Care Unit (CAN-ICU) study characterized pathogens isolated in Canadian ICUs from July 2005 to June 2006. E coli susceptibility to 10 antimicrobials was determined and a multivariate logistic regression model was designed to determine whether region, sex, isolation from a sterile site and age (younger than 30 years) were significantly associated with susceptibility to the tested antimicrobials, to multidrug resistance or pan-susceptibility. RESULTS: Four hundred ninety-three E coli isolates, representing 12.6% of all isolates collected in the CAN-ICU study were examined. Susceptibilities were highest for meropenem and tigecycline (100%), cefepime (98.2%), piperacillin-tazobactam (97.0%), ceftriaxone (93.1%) and gentamicin (92.3%), and lowest for cefazolin (76.7%), trimethoprim-sulfamethoxazole (75.7%) and the fluoroquinolones (ciprofloxacin, 78.3%; and levofloxacin, 78.9%). In the multivariate model, fluoroquinolone resistance was lowest in patients younger than 30 years of age. Cefazolin and ceftriaxone susceptibility was lowest in Nova Scotia. Susceptibility to all tested antimicrobials was lowest in Nova Scotia and British Columbia. Isolation from a sterile site was associated with trimethoprim-sulfamethoxazole, piperacillin-tazobactam and multidrug resistance. CONCLUSIONS: E coli antimicrobial susceptibility varies across Canadian ICUs. Age, region and site of infection should be considered when prescribing empirical antimicrobial therapy. For infections caused by or suspected to be caused by E coli, fluoroquinolones, cefazolin and sulfonamides should be avoided due to low susceptibilities. Local antimicrobial prescribing practices, in particular the liberal use of fluoroquinolones and cephalosporins, and inadequate infection control practices are likely reducing susceptibility rates.

Fluoroquinolone-resistant urinary isolates of Escherichia coli from outpatients are frequently multidrug resistant: results from the North American Urinary Tract Infection Collaborative Alliance-Quinolone Resistance study.

Ciprofloxacin-resistant Escherichia coli isolates (n = 1,858) from outpatient midstream urine specimens at 40 North American clinical laboratories in 2004 to 2005 were frequently resistant to ampicillin (79.8% of isolates) and trimethoprim-sulfamethoxazole (66.5%); concurrent resistance to cefdinir (9.0%) or nitrofurantoin (4.0%) was less common. Only 10.8% of isolates were resistant to ciprofloxacin alone. Fluoroquinolone-resistant isolates of E. coli from urine were frequently multidrug resistant.

Antibiotic resistance in Escherichia coli outpatient urinary isolates: final results from the North American Urinary Tract Infection Collaborative Alliance (NAUTICA).

The North American Urinary Tract Infection Collaborative Alliance (NAUTICA) study determined the antibiotic susceptibility to commonly used agents for urinary tract infections of outpatient Escherichia coli urinary isolates obtained from various geographic regions in the USA and Canada. NAUTICA involved 40 medical centres (30 from the USA and 10 from Canada). From April 2003 to June 2004 inclusive, each centre submitted up to 50 consecutive outpatient midstream urine isolates. All isolates were identified to species level by each laboratory's existing protocol. Susceptibility testing was determined using the Clinical and Laboratory Standards Institute (CLSI) microdilution method. Ampicillin (resistant>or=32 microg/mL), sulphamethoxazole/trimethoprim (SMX/TMP) (resistant>or=4 microg/mL), nitrofurantoin (resistant>or=128 microg/mL), ciprofloxacin (resistant>or=4 microg/mL) and levofloxacin (resistant>or=8 microg/mL) resistance breakpoints used were those published by the CLSI. Of the 1142 E. coli collected, 75.5% (862) were collected from the USA and 280 (24.5%) were from Canada. Patient demographics revealed a mean age of 48.1 years (range, 2 months to 99 years), with female patients representing 79.4% of patients and males representing 20.6%. Overall, resistance to ampicillin was 37.7%, followed by SMX/TMP (21.3%), nitrofurantoin (1.1%), ciprofloxacin (5.5%) and levofloxacin (5.1%). Resistance rates for all antimicrobials were higher in US medical centres compared with Canadian centres (P<0.05). Fluoroquinolone resistance was highest in patients>or=65 years of age (P<0.05). Resistance rates demonstrated considerable geographic variability both in the USA and Canada. This study reports higher rates of antibiotic resistance in US versus Canadian outpatient urinary isolates of E. coli and demonstrates the continuing evolution of resistance to antimicrobial agents.

Comparative in vitro activity of PGE 9262932 and fluoroquinolones against Canadian clinical Streptococcus pneumoniae isolates, including molecularly characterized ciprofloxacin-resistant isolates.

OBJECTIVES: The aim of this study was to assess the in vitro activity of the non-fluorinated quinolone PGE 9262932 against Streptococcus pneumoniae isolates with various resistance phenotypes: ciprofloxacin-resistant, macrolide-resistant, penicillin-resistant and trimethoprim/sulfamethoxazole-resistant. METHODS: The in vitro activity of PGE 9262932 against 2585 recent Canadian S. pneumoniae isolates with various resistance phenotypes was determined and compared with that of gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin. In particular, the activity of PGE 9262932 against ciprofloxacin-resistant isolates with defined parC and gyrA mutations was assessed. RESULTS: PGE 9262932 MIC90s were < or = 0.015 mg/L for all S. pneumoniae and 0.12 mg/L for the ciprofloxacin-resistant isolates. Resistance to penicillin, macrolides or trimethoprim/sulfamethoxazole had little effect on the PGE 9262932 MICs. The quinolone MIC50/90s were only slightly affected by the presence of one parC or gyrA mutation, but increased 2- to 16-fold in the presence of mutations in both parC and gyrA, depending on the specific quinolone. With each quinolone resistance genotype, the order of activity, based on MIC90, against the ciprofloxacin-resistant isolates was PGE 9262932, gemifloxacin, moxifloxacin, gatifloxacin and levofloxacin. CONCLUSIONS: PGE 9262932 was the most active quinolone against all S. pneumoniae isolates, regardless of resistance phenotype.

Antibiotic resistance in outpatient urinary isolates: final results from the North American Urinary Tract Infection Collaborative Alliance (NAUTICA).

The goal of the North American Urinary Tract Infection Collaborative Alliance (NAUTICA) study was to determine antibiotic susceptibility to commonly used agents for urinary tract infections against outpatient urinary isolates obtained in various geographic regions in the USA and Canada. Forty-one medical centres (30 from the USA and 11 from Canada) participated, with each centre submitting up to 50 consecutive outpatient midstream urine isolates. Isolates were identified to species level by the standard protocol of each laboratory. Susceptibility testing was determined using the National Committee for Clinical Laboratory Standards (NCCLS) microdilution method. Resistance breakpoints used were those published by the NCCLS, including: ampicillin (resistant > or = 32 microg/mL), sulphamethoxazole/trimethoprim (SMX/TMP) (resistant > or = 4 microg/mL), nitrofurantoin (resistant > or = 128 microg/mL), ciprofloxacin (resistant > or = 4 microg/mL) and levofloxacin (resistant > or = 8 microg/mL). Of the 1990 isolates collected, 75.1% (1494) were collected from the USA and 24.9% (496) were collected from Canada. The mean age of the patients was 48.3 years (range 1 month to 99 years), and 79.5% and 20.5% of isolates were obtained from women and men, respectively. The most common organisms were Escherichia coli (57.5%), Klebsiella pneumoniae (12.4%), Enterococcus spp. (6.6%), Proteus mirabilis (5.4%), Pseudomonas aeruginosa (2.9%), Citrobacter spp. (2.7%), Staphylococcus aureus (2.2%), Enterobacter cloacae (1.9%), coagulase-negative staphylococci (1.3%), Staphylococcus saprophyticus (1.2%), Klebsiella spp. (1.2%), Enterobacter aerogenes (1.1%) and Streptococcus agalactiae (1.0%). Among all 1990 isolates, 45.9% were resistant to ampicillin, 20.4% to SMX/TMP, 14.3% to nitrofurantoin, 9.7% to ciprofloxacin and 8.1% to levofloxacin. Fluoroquinolone resistance was highest in patients > or = 65 years of age. For the 1142 E. coli isolates, resistance rates were: ampicillin 37.7%, SMX/TMP 21.3%, ciprofloxacin 5.5%, levofloxacin 5.1% and nitrofurantoin 1.1%. For all 1990 isolates and for the 1142 E. coli only, resistance rates were significantly higher in US compared with Canadian medical centres. This study reports higher rates of antibiotic resistance in US versus Canadian outpatient urinary isolates and demonstrates the continuing evolution of resistance to antimicrobial agents.