Analysis of 1560 inpatient and outpatient Escherichia coli isolates from across Canada - Results from the CANWARD 2007 study CANWARD 2007

OBJeCtIveS: Escherichia coli was the most common pathogen isolated in the Canadian Ward Surveillance Study (CANWARD 2007) and remains one of the most common pathogens isolated in all health care settings. An in-depth analysis of all E coli isolates was performed to determine the distribution and demographics associated with resistance to antimicrobials, presence of extended-spectrum beta-lactamases (ESBLs) and multidrug resistance (MDR; concurrent resistance to agents from three or more different antimicrobial classes). MethODS: The CANWARD 2007 study characterized pathogens isolated from inpatient (surgical and medical wards, and intensive care units) and outpatient (emergency departments and clinics) areas of 12 Canadian hospitals between January and December 2007. E coli susceptibility to 12 antimicrobials was determined, ESBL production was determined, and a multivariate nominal logistic regression model was designed to determine if sex, isolation from a sterile site, inpatient versus outpatient status, and age were significantly associated with susceptibility to the tested antimicrobials, MDR or ESBL production. ReSuLtS: In total, 1702 E coli isolates, representing 21.6% of all isolates collected in the CANWARD 2007 study, were investigated. Of these, 1560 isolates fell within the primary objective of the study and were included in the present analysis. Susceptibilities were greater than 90% for meropenem (100%), ertapenem (100%), tigecycline (99.9%), piperacillin-tazobactam (97.9%), cefepime (97.9%), ceftriaxone (95.4%), nitrofurantoin (95.2%), cefoxitin (94.8%), amoxicillinclavulanate (92.9%) and gentamicin (91.4%). Cefazolin (89.4%), the fluoroquinolones (ciprofloxacin, 79.4%; levofloxacin, 79.9%) and trimethoprim-sulfamethoxazole (75.7%) were less active agents. In the multivariate model, invasive isolates were significantly associated with lower susceptibility rates for trimethoprim-sulfamethoxazole. Increasing age was associated with lower susceptibility to fluoroquinolones, ceftriaxone, cefepime, gentamicin and nitrofurantoin, as well as ESBL production. Sex was not associated with resistance to any antimicrobial or to ESBL production. Inpatient status was associated with higher resistance rates to amoxicillin-clavulanate, cefazolin, fluoroquinolones and trimethoprim-sulfamethoxazole. Isolation of an ESBL producer was only found to be independently associated with age, being more common in older patients. MDR was not found to be associated with any variable measured when ESBL producers were excluded from analysis. CONCLuSIONS: E coli antimicrobial susceptibility varies according to patient factors. Age and inpatient status were the most important determinants in the present analysis and should be considered when prescribing empirical antimicrobial therapy. Fluoroquinolones and sulfonamides should be used cautiously and in consideration of local resistance patterns for infections caused by E coli, due to lower susceptibility rates. Independent factors associated with antimicrobial resistance were age, inpatient status and isolation from a sterile site. These factors should be considered when empirically treating infections likely caused by E coli. Local antimicrobial prescribing practices, in particular the liberal use of fluoroquinolones, and inadequate infection control practices may be reducing susceptibility rates. OBJeCtIFS : L'Escherichia coli était le pathogène le plus isolé dans l'étude CANWARD 2007 sur la surveillance des services aux hospitalisés canadiens et demeure l'un des pathogènes les plus isolés en milieu de santé. On a effectué une analyse approfondie de tous les isolats d'E coli pour déterminer la répartition et la démographie associées à la résistance aux antimicrobiens ainsi qu'à la présence de bêta-lactamases à large spectre (ESBL) et de multirésistance (résistance conjointe à au moins trois classes d'antimicrobiens). MÉthODOLOGIe : L'étude CANWARD 2007 caractérisait les pathogènes isolés de patients hospitalisés (service de chirurgie, service médical et unité de soins intensifs) et ambulatoires (urgence et cliniques) de 12 hôpitaux canadiens entre janvier et décembre 2007. On a déterminé la susceptibilité de l'E coli à 12 antimicrobiens ainsi que la production d'ESBL et conçu un modèle de régression logistique nominale multivariée pour déterminer si le sexe, l'isolement d'un foyer stérile, le statut de patient hospitalisé ou ambulatoire et l'âge s'associaient de manière significative à la susceptibilité aux antimicrobiens vérifiés, à la multirésistance ou à la production d'ESBL. RÉSuLtAtS : Au total, on a évalué 1 072 isolats d'E coli, représentant 21,6 % de tous les isolats prélevés dans le cadre de l'étude CANWARD 2007. De ce nombre, 1 560 isolats respectaient l'objectif primaire de l'étude et ont été inclus dans la présente analyse. Les susceptibilités étaient supérieures à 90 % pour le méropénem (100 %), l'ertapénem (100 %), la tigécycline (99,9 %), la pipéracilline-tazobactam (97,9 %), la céfépime (97.9 %), la ceftriaxone (95,4 %), la nitrofurantoïne (95,2 %), la céfoxitine (94,8 %), l'amoxicilline-clavulanate (92,9 %) et la gentamicine (91,4 %). La céfazoline (89,4 %), les fluoroquinolones (ciprofloxacine, 79,4 %, lévofloxacine, 79,9 %) et le triméthoprim-sulfaméthoxazole (75,7 %) étaient moins actifs. Dans le modèle multivarié, les isolats envahissants étaient associés de manière marquée à des taux de susceptibilité plus faibles pour le triméthoprim-sulfaméthoxazole. Le vieillissement s'associait à une susceptibilité plus faible aux fluoroquinolones, à la ceftriaxone, à la suite page suivante Lagacé-Wiens et al Can J Infect Dis Med Microbiol Vol 20 Suppl A Spring 2009 50A E scherichia coli is the most commonly isolated clinically relevant Gram-negative organism in most health care settings (1-3). Although most commonly associated with urinary tract infections, all body sites can be involved. Furthermore, resistance to multiple antimicrobials is increasing and multidrug resistant (MDR; concurrent resistance to agents from three or more different antimicrobial classes) isolates are common (1,4,5). Appropriate empirical antimicrobial choice must take into account local resistance patterns and other demographic variables such as patient age, site and severity of infection, sex, inpatient status as well as previous antimicrobial use, stay in hospitals or personal care homes, and colonization with antimicrobial resistant organisms (1,6). The purpose of the present study was to provide an in-depth analysis of patient factors associated with drug resistance in the most commonly isolated organism overall in Canadian hospitals. MethODS E coli isolates were obtained as part of the Canadian Ward Surveillance Study (CANWARD 2007), which collected isolates submitted to 12 clinical microbiology laboratories from tertiary care hospitals in seven provinces across Canada. Submitting sites and collection strategy are described elsewhere in the present supplement (2). Isolates had to be deemed clinically significant by the referring laboratory's current specimen work-up protocol. Demographic information collected with each isolate included patient age, sex, site of infection and the location of patient contact (surgical or medical ward, emergency room, intensive care unit [ICU] or hospital clinic). A minimum number of isolates from each hospital location and anatomical site was requested to provide more power to the study. The implication of this collection strategy is that the anatomical distribution of pathogen isolation and inpatient versus outpatient distribution does not reflect the true distribution in the population studied. Isolates were collected within both primary and secondary study objectives and only isolates collected within the primary objective were considered in this analysis. For statistical analysis, age was divided into four categories: 20 years and younger, 21 to 60 years, 61 to 80 years, and 81 years and older, and location of patient contact was divided into either inpatient (wards and ICUs) or outpatient (emergency room and clinics). Information on previous antimicrobial exposure, hospitalization duration and underlying medical conditions was not available. Antimicrobial susceptibility to amoxicillin-clavulanate, cefazolin, cefepime, ceftriaxone, ciprofloxacin, gentamicin, nitrofurantoin, levofloxacin, meropenem, ertapenem, piperacillin-tazobactam, tigecycline and trimethoprim-sulfamethoxazole was determined using broth dilution as described elsewhere in the present supplement (2). Screening for ESBL production was achieved using a 1 µg/mL or greater ceftriaxone breakpoint and confirmation was with the Clinical and Laboratory Standards Institute-recommended disk diffusion method (7). Univariate analysis using the c 2 (or Fisher's exact test where required) was undertaken to identify relationships between susceptibility to each of the antimicrobials and ESBL production; and the following variables: sex, age group, inpatient/outpatient status and isolation from a sterile site (blood, cerebrospinal fluid, synovial fluid). Relationships where the P<0.20 in the univariate analysis were included in a multivariate nominal logistic regression model to determine independent explanatory variables. Initially, a full factorial multiple logistic regression analysis was performed using the potential explanatory variables identified in the univariate analysis for each antimicrobial, and then a backward selection so that all factors remaining in the model were statistically significant at a 5% level (P<0.05). Statistical analysis was undertaken using JMP software version 7.0 (SAS Institute Inc, USA). ReSuLtS Of 7881 total organisms, 1702 E coli (21.6%) were collected from the CANWARD 2007 study, making it the most common organism isolated from patients in Canadian hospitals overall. Of these, 1560 fell within the primary objective and the remaining 142 were submitted as putative ESBL producers for separate analysis and excluded from the present analysis. The mean age of patients infected with E coli was 56.9 years; 12.3% of E coli isolates were from patients younger than 21 years, 34.7% were 21 to 60 years of age, 33.9% were 61 to 80 years of age and 19.1% were older than 80 years of age. There were more samples from women (59.3%); with both sexes combined, 50.5% were invasive isolates (all bloodstream), and 40.7% were from urine, 6.4% from respiratory sources and 2.4% from wounds. Note that the sampling strategy was biased to include a surplus of bloodstream isolates to have greater numbers of these for analysis and this does not represent the true source distribution of E coli infections. The distribution among provinces was British Columbia, 9.7%; Alberta, 7.6%; Saskatchewan, 9.1%; Manitoba, 9.2%; Ontario, 28.3%; Quebec, 29.2% and Nova Scotia, 6.9%. Isolates were not obtained from Newfoundland, Nunavut, the Northwest Territories, Yukon, New Brunswick or Prince Edward Island. Minimum inhibitory concentrations (MICs) required to inhibit 50% and 90% of organisms (MIC 50 , MIC 90 ) and percentage of isolates susceptible to the antimicrobials are provided in Resistance in E coli from Canadian inpatients and outpatients Can J Infect Dis Med Microbiol DISCuSSION Low susceptibility of ICU E coli isolates to fluoroquinolones and trimethoprim-sulfamethoxazole was not unexpected given the wide use of these antimicrobials in both inpatients and outpatients. In particular, the dramatic increase in fluoroquinolone resistance has been observed in many settings (8-10). Our observations suggest that first-generation cephalosporins and amoxicillin-clavulanate are still useful agents for infections caused by E coli in that susceptibility rates remain near 90% overall. This is particularly true of outpatient isolates where susceptibility is greater than 90% for both these agents. On the contrary, low susceptibility to fluoroquinolones even in the outpatient setting (84%) begins to bring into question the use of these agents as first line for infections commonly caused by E coli, such as urinary tract infections. Trimethoprimsulfamethoxazole susceptibility rates are below 80% in both inpatient and outpatient settings and should only be used for infections empirically in the context of supportive data from local antibiograms or definitive susceptibility data. In our multivariate model, increasing age was independently associated with reduced susceptibility to fluoroquinolones, nitrofurantoin, ceftriaxone, cefepime, gentamicin and ESBL production. The association between age and fluoroquinolone susceptibility has been demonstrated previously and is likely due to increasing exposure to fluoroquinolones over time and avoidance of fluoroquinolone use in children Predictably, inpatient isolates had lower susceptibility to several antibiotics, including amoxicillin-clavulanate, fluoroquinolones, cefazolin and trimethoprim-sulfamethoxazole. Interestingly, susceptibility to antimicrobials commonly used in the inpatient setting (ceftriaxone, cefepime, gentamicin, carbapenems and piperacillin-tazobactam) did not appear to be significantly affected by inpatient status. This is reassuring in that these antimicrobials maintain good activity overall in the hospital setting. The reason that antimicrobials commonly used in the community are most affected by inpatient status is not known, but may be due to general practitioners using these antimicrobials to treat outpatients and selection bias occurring because poor response due to antimicrobial resistance requires admission for parenteral antimicrobials. Interestingly, sex was not a predictor of susceptibility to any of the antimicrobials tested after adjusting for other factors in the multivariate model. Although large differences were seen between susceptibility to fluoroquinolones, both inpatient status and age appeared to be confounding factors in the effect of sex on fluoroquinolone resistance. The absence of a sex effect contradicts the findings of others Meropenem, ertapenem, piperacillin-tazobactam, tigecycline and cefoxitin were not significantly associated with any demographic variable in the multivariate model. Low overall resistance rates accounts for these observations. Our study had some limitations. We could not collect patient information such as length of stay, previous antimicrobial exposure and underlying disease. Although of great interest for the prediction of antimicrobial resistance, the effect of these variables cannot be determined with our data. Also, our isolates reflect only information from the 12 centres studied and our data may not reflect the antimicrobial susceptibility patterns of all hospitals in Canada. However, this study does provide valuable information about the factors predicting antimicrobial susceptibility of E coli in one of the largest of inpatient and outpatient populations in Canada studied to date

Antimicrobial-resistant Streptococcus pneumoniae in Canadian hospitals: Results from the 2007 CANWARD study CANWARD 2007

Canadian hospitals to a range of antimicrobial agents. The present paper focuses on antimicrobial resistance in Streptococcus pneumoniae in Canadian hospitals, with an emphasis on macrolide resistance. METHODS: Minimum inhibitory concentrations of antimicrobial agents were determined using the broth microdilution method and interpreted according to Clinical and Laboratory Standards Institute breakpoints. Macrolide-nonsusceptible strains (clarithromycin minimum inhibitory concentrations 0.5 µg/mL or greater) were analyzed by multiplex polymerase chain reaction for the presence of mefA and ermB genes. RESULTS: S pneumoniae represented 9.0% (706 of 7881) of all isolates collected in CANWARD 2007. Of the 706 S pneumoniae isolates collected, 33.1% (234) were from blood and 66.9% (472) were from respiratory specimens. The overall resistance (resistant and intermediate) rates for S pneumoniae isolated from respiratory and blood specimens, respectively, were: penicillin (23.9%, 14.4%), clarithromycin (22.1%, 12.6%), trimethoprim-sulfamethoxazole (14.7%, 11.5%), doxycycline (7.8%, 5.1%) and clindamycin (7.1%, 3.3%). Multidrug resistance (resistance to penicillin, clarithromycin and trimethoprimsulfamethoxazole) accounted for 2% (n=9) and 0.5% (n=1) of respiratory and blood isolates, respectively. Susceptibility of 95% or greater was found with amoxicillin-clavulanic acid (99.5%, 99.3%), ceftriaxone (99.5%, 100%), cefuroxime (95.0%, 96.8%), ertapenem (99.8%, 100%), meropenem (96.1%, 99.5%) and levofloxacin (99.1%, 100%) for respiratory and blood specimens, respectively. No resistance to vancomycin, tigecycline, cethromycin or telithromycin was found. mefA was present in 53.6% (52 of 97) of respiratory and 59.3% (16 of 27) of blood macrolide-nonsusceptible S pneumoniae, while ermB was present in 38.1% (37 of 97) of respiratory and 37% (10 of 27) of blood isolates. Eight of 97 (8.2%) respiratory and one of 27 (3.7%) blood isolates contained both mefA and ermB genes. CONCLUSIONS: S pneumoniae is a common organism isolated from clinical specimens in Canadian hospitals. Resistance was highest t

Ciprofloxacin or imipenem use correlates with resistance in Pseudomonas aeruginosa

GG Zhanel, LE Nicolle, AS Gin, J Karlowsky, A Kabani, DJ Hoban. Ciprofloxacin or imipenem use correlates with resistance in Pseudomonas aeruginosa. Can J Infect Dis 1998;9(6):382-386. OBJECTIVE: To investigate the relationship between ciprofloxacin or imipenem use and antimicrobial resistance in Pseudomonas aeruginosa. METHODS: A retrospective review of monthly antimicrobial susceptibility reports for ciprofloxacin (1988 to 1995) and imipenem (1987 to 1995) against P aeruginosa and hospital antimicrobial use records at a tertiary care teaching hospital in Winnipeg, Manitoba. Data were entered into a relational database, R:Base 4.5++, collated, transferred to a spreadsheet and subjected to linear regression analysis. The relationship between ciprofloxacin or imipenem use and resistance was assessed using a Pearson correlation. RESULTS: Ciprofloxacin-resistant P aeruginosa increased from 1.0% of all isolates in 1988 to 10.0% in 1995. A significant (P=0.05) correlation was demonstrated between the amount of ciprofloxacin use and prevalence of ciprofloxacin-resistant P aeruginosa (r=0.73, P=0.05). Imipenem-resistant P aeruginosa increased from 1.0% of isolates in 1987 to a maximum of 10.4% in 1991, and subsequently decreased to 5.4% in 1995. Imipenem use and the prevalence of imipenem-resistant P aeruginosa were significantly correlated (r=0.85, P=0.014). CONCLUSIONS: Ciprofloxacin use was directly associated with ciprofloxacin resistance, and imipenem use was directly associated with imipenem resistance in P aeruginosa. voir page suivante A ntimicrobial resistance is a global problem of increasing concern (1,2). Infection caused by antimicrobialresistant organisms is associated with increased morbidity and mortality, and increased length of hospital stay (1,2). The increasing prevalence of antimicrobial resistance has been associated with a number of factors, including increasing numbers of immunocompromised patients in hospitals, increasing use of invasive clinical procedures, world travel leading to rapid dissemination of antimicrobial-resistant organisms and intense antimicrobial use (1,2). Although there appears to be a relationship between antimicrobial use and the development of resistance PATIENTS AND METHODS The study was conducted at the Health Sciences Centre Winnipeg, Manitoba from January 1987 to December 1995. The Health Sciences Centre is an 850-bed tertiary care referral institution. It is the main teaching hospital in Manitoba (population 1,200,000), with over 22,000 admission per year. Clinical programs at the Health Sciences Centre include intensive care units (medical, surgical, paediatric and neonatal), a burn unit, major cancer treatment centre, cardiovascular surgery program, transplant program (bone marrow, renal and lung) and cystic fibrosis program. P aeruginosa (out-patient and in-patient isolates) isolated from all sites, including blood (1.5% of isolates), urine (20% of isolates) and other, such as sputum, wound and body fluids (for example, pleural fluid) (78.5% of isolates) were included. Repeat isolates from the same patient were included if they were identified more than seven days apart. Over the eightyear study period (1987 to 1995), the same commercial microdilution system was used. Autoscan 4 (American Microscan, California), together with Microscan commercially prepared conventional panels were used for antimicrobial susceptibility testing. Minimal inhibitory concentration (MIC) breakpoints for defining susceptibility, intermediate susceptibility and resistance were 1 m g/mL or less, 2 m g/mL and 4 m g/mL or greater for ciprofloxacin, and 4 m g/mL or less, 8 m g/mL and 16 m g/mL or greater for imipenem, respectively (6). Thus, ciprofloxacinand imipenem-resistant isolates had MICs 4 m g/mL or greater and 1 6 m g/mL or greater, respectively. During the study period, both ciprofloxacin and imipenem were classified as 'restricted' agents requiring Section of Infectious Diseases verbal approval (oral ciprofloxacin) or formal Infectious Diseases consultation (parenteral ciprofloxacin, imipenem). Data from monthly Microscan reports from 1988 to 1995 (ciprofloxacin) and 1987 to 1995 (imipenem) were reviewed and entered into a relational database (R:Base 4.5++, Microrim, Washington). Data were collated and exported into the Excel (Microsoft, Washington) spreadsheet program for further analysis. Statistical analysis using linear regression was conducted using the Number Cruncher Statistical System (NCSS, Utah). The relationship between ciprofloxacin and imipenem use, and resistance was assessed using a Pearson correlation. Ciprofloxacin and imipenem use were based on drug purchase data obtained from the pharmacy department. RESULTS Ciprofloxacin: Ciprofloxacin was introduced into the hospital formulary in late 1987. Usage increased from 1988 to 1990 inclusive, as did the prevalence of ciprofloxacin-resistant P aeruginosa (1% to 7.3%) Can J Infect Dis Vol 9 No 6 November/December 1998 383 Antibiotic use correlates with resistance RÉSULTATS : Lles souches de P. aeruginosa résistantes à la ciprofloxacine ont augmenté de 1 % de tous les isolats en 1988 à de 10 % en 1995. Une corrélation significative (P = 0,05) a été démontrée entre la quantité de ciprofloxacine utilisée et la prévalence des souches de P. aeruginosa qui lui sont résistantes (r = 0,73, P = 0,05). Les souches de P. aeruginosa résistantes à l'imipénème sont passées de 1 % des isolats en 1987 à un maximum de 10,4 % en 1991, avant de diminuer à 5,4 % en 1995. L'emploi de l'imipénème et la prévalence des souches de P. aeruginosa résistantes à l'imipénème se sont révélés être en corrélation significative (r = 0,85, P = 0,014). CONCLUSIONS : L'emploi de la ciprofloxacine et l'emploi de l'imipénème ont été directement associés à la résistance de P. aeruginosa à leur endroit. DISCUSSION P aeruginosa is an important nosocomial pathogen that is characterized by its propensity to develop antimicrobial resistance. Our experience documents a significant correlation between the use of two broad-spectrum antimicrobials, ciprofloxacin and imipenem, and resistance to P aeruginosa. As ciprofloxacin use increased, the prevalence of resistant isolates also increased, while as ciprofloxacin use stabilized or decreased, the development of ciprofloxacin-resistant P aeruginosa stabilized or decreased, respectivel