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

The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tonz Syndrome

Kohlschutter-Tönz syndrome (KTS) is a rare autosomal-recessive disorder of childhood onset characterized by global developmental delay, spasticity, epilepsy, and amelogenesis imperfecta. Rogdi, an essential protein, is highly conserved across metazoans, and mutations in Rogdi are linked to KTS. However, how certain mutations in Rogdi abolish its physiological functions and cause KTS is not known. In this study, we determined the crystal structure of human Rogdi protein at atomic resolution. Rogdi forms a novel elongated curved structure comprising the ?? domain, a leucine-zipper-like four-helix bundle, and a characteristic ??-sheet domain. Within the ?? domain, the N-terminal H1 helix (residues 19-45) pairs with the C-terminal H6 helix (residues 252-287) in an antiparallel manner, indicating that the integrity of the four-helix bundle requires both N- and C-terminal residues. The crystal structure, in conjunction with biochemical data, indicates that the ?? domain might undergo a conformational change and provide a structural platform for protein-protein interactions. Disruption of the four-helix bundle by mutation results in significant destabilization of the structure. This study provides structural insights into how certain mutations in Rogdi affect its structure and cause KTS, which has important implications for the development of pharmaceutical agents against this debilitating neurological disease

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Revisión de la literatura integradora acerca de intervenciones de la enfermería volcadas hacia el incremento del autocuidado entre pacientes con insuficiencia cardiaca

Objective: to analyze and summarize knowledge concerning critical components of interventions that have been proposed and implemented by nurses with the aim of optimizing self-care by heart failure patients.Methods: PubMed and CINAHL were the electronic databases used to search full peer-reviewed papers, presenting descriptions of nursing interventions directed to patients or to patients and their families and designed to optimize self-care. Forty-two studies were included in the final sample (n=4,799 patients).Results: this review pointed to a variety and complexity of nursing interventions. As self-care encompasses several behaviors, interventions targeted an average of 3.6 behaviors. Educational/counselling activities were combined or not with cognitive behavioral strategies, but only about half of the studies used a theoretical background to guide interventions. Clinical assessment and management were frequently associated with self-care interventions, which varied in number of sessions (1 to 30); length of follow-up (2 weeks to 12 months) and endpoints.Conclusions: these findings may be useful to inform nurses about further research in self-care interventions in order to propose the comparison of different modalities of intervention, the use of theoretical background and the establishment of endpoints to evaluate their effectiveness.Objetivo:analisar e sintetizar o conchecimento relacionado aos componentes críticos das intervençoes que têm, sido propostas e implementadas por enfermeiros(as) com objetivo de optimizar o auto-cuidado de pacientes portadores de insuficiência cardíaca.Método:PubMed e CINAHL foram as bases de dados electrônicas utilizadas para investigar artigos revisados por pares (peer review), apresentando as descrições das intervenções dirigidas ao paciente ou ao paciente e sua familia, visando melhorar o auto-cuidado. Foram incluídos 42 estudos na amostra final (n=4799 pacientes).Resultados:esta revisão apontou variedade e complexidade das intervenções de enfermagem. Como o auto-cuidado envolve diferentes comportamentos, as intervenções visaram em média 3,6 comportamentos. As Atividades de educação e aconselhamento foram combinadas ou não com estratégias cognitivo-comportamentais, mas somente a metade dos estudos utilizaram suporte teórico para guiar as intervenções. A avaliação e o manejo clínico foram frequentemente associados às intervenções de auto-cuidado, as quais variam em número de sessões (1 a 30), duração do seguimento (2 semanas a 12 meses) e desfechos.Conclusão:estes resultados podem ser úteis para guiar os enfermeiros no que se refere à futuros estudos sobre intervenções de auto-cuidado, de maneira a propor a comparação de diferentes modalidades de intervenção, uso de suporte teórico e estabelecimento de desfechos para melhor avaliar sua eficácia.Objetivo:analizar y sintetizar el conocimiento relacionado a componentes críticos de intervenciones que han sido propuestas e implementadas por enfermeros(as) con el objetivo de optimizar el autocuidado entre pacientes con insuficiencia cardiaca.Método:PUBMED y CINAHL han sido las bases de datos electrónicas usadas para investigar artículos revisados por pares (peer review), presentando descripciones de intervenciones destinadas a perfeccionar el autocuidado dirigido al paciente o al paciente y a su familia. Se incluyeron 42 estudios en la muestra final (n=4799 pacientes).Resultados:esta revisión apuntó a una variedad y complejidad de intervenciones de enfermería. Como el autocuidado abarca varios comportamientos, las intervenciones tuvieron como blanco, en media, 3,6 comportamientos. Actividades de educación/consejería fueron combinadas o no con estrategias cognitivo-comportamentales, pero tan solo cerca de la mitad de los estudios tenían aporte teórico para guiar intervenciones. La gestión y la evaluación clínica fueron frecuentemente asociadas a intervenciones de autocuidado, las cuales oscilaron en número de sesiones (1 a 30), duración del seguimiento (2 semanas a 12 meses) y objetivos.Conclusiones:estos resultados pueden ser útiles para informar a las enfermeras acerca de nuevas investigaciones en intervenciones de autocuidado, de modo a proponer la comparación de distintas modalidades de intervención, el uso de un aporte teórico y el establecimiento de objetivos para evaluar su eficacia

Whole genome SNP-associated signatures of local adaptation in honeybees of the Iberian Peninsula

The availability of powerful high-throughput genomic tools, combined with genome scans, has helped identifying genes and genetic changes responsible for environmental adaptation in many organisms, including the honeybee. Here, we resequenced 87 whole genomes of the honeybee native to Iberia and used conceptually different selection methods (Samβada, LFMM, PCAdapt, iHs) together with in sillico protein modelling to search for selection footprints along environmental gradients. We found 670 outlier SNPs, most of which associated with precipitation, longitude and latitude. Over 88.7% SNPs laid outside exons and there was a significant enrichment in regions adjacent to exons and UTRs. Enrichment was also detected in exonic regions. Furthermore, in silico protein modelling suggests that several non-synonymous SNPs are likely direct targets of selection, as they lead to amino acid replacements in functionally important sites of proteins. We identified genomic signatures of local adaptation in 140 genes, many of which are putatively implicated in fitness-related functions such as reproduction, immunity, olfaction, lipid biosynthesis and circadian clock. Our genome scan suggests that local adaptation in the Iberian honeybee involves variations in regions that might alter patterns of gene expression and in protein-coding genes, which are promising candidates to underpin adaptive change in the honeybee.John C. Patton, Phillip San Miguel, Paul Parker, Rick Westerman, University of Purdue, resequenced the 87 whole genomes of IHBs. Jose Rufino provided computational resources at IPB. Analyses were performed using the computational resources at the Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX), Uppsala University. DH was supported by a PhD scholarship (SFRH/BD/84195/2012) from the Portuguese Science Foundation (FCT). MAP is a member of and receives support from the COST Action FA1307 (SUPER-B). This work was supported by FCT through the programs COMPETE/QREN/EU (PTDC/BIA-BEC/099640/2008) and the 2013-2014 BiodivERsA/FACCE-JPI (joint call for research proposals, with the national funders FCT, Portugal, CNRS, France, and MEC, Spain) to MAP

Possible Associations of NTRK2 Polymorphisms with Antidepressant Treatment Outcome: Findings from an Extended Tag SNP Approach

Background: Data from clinical studies and results from animal models suggest an involvement of the neurotrophin system in the pathology of depression and antidepressant treatment response. Genetic variations within the genes coding for the brain-derived neurotrophic factor (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment. Methods: We performed a single and multi-marker association study with antidepressant treatment outcome in 398 depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Two Caucasian replication samples (N = 249 and N = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the BDNF gene region and 64 tagging SNPs in the NTRK2 gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples. Results: In the discovery analysis, 7 BDNF SNPs and 9 NTRK2 SNPs were nominally associated with treatment response. Three NTRK2 SNPs (rs10868223, rs1659412 and rs11140778) also showed associations in at least one replication sample and in the combined sample with the same direction of effects ($P_{corr}$ = .018, $P_{corr}$ = .015 and $P_{corr}$ = .004, respectively). We observed an across-gene BDNF-NTRK2 SNP interaction for rs4923468 and rs1387926. No robust interaction of associated SNPs was found in an analysis of BDNF serum protein levels as a predictor for treatment outcome in a subset of 93 patients. Conclusions/Limitations: Although not all associations in the discovery analysis could be unambiguously replicated, the findings of the present study identified single nucleotide variations in the BDNF and NTRK2 genes that might be involved in antidepressant treatment outcome and that have not been previously reported in this context. These new variants need further validation in future association studies

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

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 &apos;restricted&apos; 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&apos;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&apos;emploi de l&apos;imipénème et la prévalence des souches de P. aeruginosa résistantes à l&apos;imipénème se sont révélés être en corrélation significative (r = 0,85, P = 0,014). CONCLUSIONS : L&apos;emploi de la ciprofloxacine et l&apos;emploi de l&apos;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

A cross Canada surveillance of antimicrobial resistance in respiratory tract pathogens

OBJECTIVE: To determine the prevalence of antimicrobial resistance in clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis from medical centres across Canada. METHODS: Fifty laboratories from across Canada were asked to collect up to 25 consecutive clinical isolates of S pneumoniae, H influenzae and M catarrhalis at some time between September 1994 and May 1995, and then again between September and December of 1996. A total of 2364 S pneumoniae, 575 H influenzae and 200 M catarrhalis samples were collected. H influenzae and M catarrhalis isolates were tested for the production of beta-lactamase. S pneumoniae isolates were characterized as penicillin susceptible, intermediately resistant or high level penicillin-resistant. Minimal inhibitory concentrations (MICs) were determined using a microbroth dilution technique described by the National Committee of Clinical Laboratory Standards. RESULTS: Between the two collection periods, there was a significant increase in highly penicillin-resistant S pneumoniae from 2.1% to 4.4% (P&lt;0.05) and an increase in intermediately penicillin-resistant strains from 6.4% to 8.9% (P&lt;0.05). A significant increase in high level penicillin-resistant S pneumoniae was noted among paediatric isolates. No significant difference in the susceptibilities of comparator agents was detected. A significant increase in the number of beta-lactamase producing H influenzae, 34% to 43% (P&lt;0.05) was observed. Ninety-five per cent of M catarrhalis isolates were beta-lactamase producers in both time periods. see next page S treptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the most common bacterial pathogens associated with upper respiratory tract infections in both children and adults (1,2). These pathogens are frequently the causative agents in community-acquired pneumonia, acute sinusitis, acute exacerbation of chronic bronchitis, otitis media and meningitis. Worldwide increases in antimicrobial resistance and the changing epidemiology of pathogenic strains have required a change in the approach to treatment of infections due to these organisms. Because rapid, sensitive and specific diagnostic tests are not available for the common respiratory bacterial pathogens, choice of antimicrobial therapy is nearly always empirical. Thus, it is essential to monitor rates of resistance to such pathogens so that the most efficacious agent can be used. The present study was performed to determine the rates of antimicrobial resistance to three respiratory tract pathogens from across Canada. Centres that had previously provided isolates to determine resistance rates in various pathogens were asked to participate in the present study. Specifically, the rates of penicillin susceptibility in S pneumoniae and betalactamase production in H influenzae and M catarrhalis were determined. As well, the in vitro activities of selected antimicrobial agents were determined against all three pathogens. METHODS Fifty laboratories from across Canada were asked to collect up to 25 consecutive clinical isolates of S pneumoniae, H influenzae and M catarrhalis at some time between September 1994 and May 1995, and then again between September and December of 1996. A total of 2364 S pneumoniae, 575 H influenzae and 200 M catarrhalis samples were collected. Almost all centres were tertiary care centres that served urban areas. All isolates were sent to Mount Sinai Hospital (Toronto, Ontario) microbiology laboratory for analysis. All isolates were nonsterile respiratory tract specimens that were predominately sputum cultures (greater than 90%). Only single isolates from different patients were included in the study. Study sites were asked to provide information on the patient&apos;s age and site of isolation. Isolates were identified using standard criteria (3). H influenzae were serotyped to determine whether they were type b using a commercial latex agglutination serotyping kit (Difco Laboratories, Michigan). H influenzae and M catarrhalis isolates were tested for the production of beta-lactamase by the cefinase disk method (Becton Dickinson Microbiology Systems, Maryland) (4). Minimal inhibitory concentrations (MICs) were determined using a microbroth dilution technique described by the National Committee of Clinical Laboratory Standards (NCCLS) (Villanova, Pennsylvania) (5). The susceptible, intermediate and resistant breakpoints for determining penicillin susceptibility of S pneumoniae were: susceptible 0.06 mg/L or less, intermediate 0.12 to 1 mg/L and resistant 2.0 mg/L or greater. The following antimicrobials were evaluated: cefprozil (Cefzil, Bristol-Myers Squibb Canada Inc), cefaclor (Ceclor, Eli Lilly Canada Inc), cefixime (Suprax, Rhône-Poulenc Rorer Canada Inc), cephalexin (Keflex, Eli Lilly Canada Inc), cefuroxime (Zinacef, Glaxo Wellcome Canada Inc), ampicillin, clarithromycin (Biaxin, Abbott), azithromycin (Zithromax, Pfizer Canada), erythromycin and ciprofloxacin (Cipro, Bayer Inc). Erythromy- Can J Infect Dis Vol 10 No 2 March/April 1999 129 Antimicrobial resistance in respiratory pathogens CONCLUSIONS: During the course of this study, the incidence of penicillin resistance in S pneumoniae doubled. As a result of this increase, infections due to this organism in sites where poor penetration of beta-lactam antibiotics occur may become increasingly difficult to manage. RÉSULTATS : Entre les deux périodes de cueillette, on a noté une augmentation significative du nombre de souches de S. pneumoniae très résistantes à la pénicilline, qui est passée de 2,1 % à 4,4 % (p &lt; 0,05) et une augmentation de 6,4 % à 8,9 % (p &lt; 0,05) des souches moyennement résistantes à la pénicilline. Une augmentation significative des souches de S. pneumoniae très résistantes à la pénicilline a été notée parmi les spécimens pédiatriques. Aucune différence significative n&apos;a été notée entre les agents de comparaison. Une augmentation significative du nombre de souches de H. influenzae productrices de bêta-lactamases a été observée, soit de 34 % à 43 % (p &lt; 0,05). Quatre-vingt-quinze pour cent des isolats de M. catarrhalis étaient producteurs de bêta-lactamases pendant les deux périodes en question. CONCLUSION : Durant l&apos;étude, l&apos;incidence de la résistance de S. pneumoniae à la pénicilline a doublé. Par conséquent, les infections attribuables à cet organisme, là où la pénétration des bêta-lactamines est faible, pourraient devenir plus difficiles à traiter. cin, ampicillin, clindamycin, tetracycline, chloramphenicol, and trimethoprim/sulphamethoxazole (TMP/SMX) were obtained from Sigma Chemical Company (Michigan). RESULTS Of 3139 clinical isolates, S pneumoniae accounted for 75% (2364) of the isolates, 18.5% (575) were H influenzae, and the remaining 6.5% (or should be 6%) (200) were M catarrhalis. More than 90% of specimens were isolated from sputum samples. Overall, approximately 40% of the S pneumoniae isolates were from a paediatric (age birth to 16 years) population, and 60% originated from adults during both time periods. In 1994-95, 91.4% of S pneumoniae strains were penicillin susceptible, 6.4% were intermediately resistant and 2.1% were highly resistant to penicillin All agents tested had excellent activity against penicillinsusceptible strains. Among intermediately resistant strains, high rates of resistance were observed for erythromycin (12.9%), TMP/SMX (65.6%), cefuroxime (42.4%) and tetracy- Beta-lactamase was detected in 34% of H influenzae strains in 1994-95 and 43% in 1996. Of the 575 isolates that were collected, only three strains were serotype b. Two of these were isolated from adults and one from a child. Forty-four per cent of the H influenzae isolates were from a paediatric population, the remaining 56% were from adults. For beta-lactamase negative H influenzae, all agents had good activity. Ninety-six per cent of beta-lactamase producing H influenzae were resistant to ampicillin, and 13.7% were resistant to TMP/SMX Beta-lactamase production was detected in 95% of the M catarrhalis isolate