Impact of accessory gene regulator (agr) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant Staphylococcus aureus

<p>Abstract</p> <p>Background</p> <p>The accessory gene regulator (<it>agr</it>) is a quorum sensing cluster of genes which control colonization and virulence in <it>Staphylococcus aureus</it>. We evaluated <it>agr </it>function in community- (CA) and healthcare-associated (HA) MRSA, to compare the pharmacodynamics and bactericidal activity of vancomycin against <it>agr </it>functional and dysfunctional HA-MRSA and CA-MRSA.</p> <p>Methods</p> <p>40 clinical isolates of MRSA from the Canadian Nosocomial Infection Surveillance Program were evaluated for delta-haemolysin production, as a surrogate marker of <it>agr </it>function. Time kill experiments were performed for vancomycin at 0 to 64 times the MIC against an initial inoculum of 10⁶and 10⁸cfu/ml of <it>agr </it>functional and dysfunctional CA-MRSA and HA-MRSA and these data were fit to a hill-type pharmacodynamic model.</p> <p>Results</p> <p>15% isolates were <it>agr </it>dysfunctional, which was higher among HA-MRSA (26.3%) versus CA-MRSA (4.76%). Against a low initial inoculum of 10⁶cfu/ml of CA-MRSA, vancomycin pharmacodynamics were similar among <it>agr </it>functional and dysfunctional strains. However, against a high initial inoculum of 10⁸cfu/ml, killing activity was notably attenuated against <it>agr </it>dysfunctional CA-MRSA (USA400) and HA-MRSA (USA100). CA-MRSA displayed a 20.0 fold decrease in the maximal reduction in bacterial counts (Emax) which was 3.71 log₁₀CFU/ml for <it>agr </it>functional vs. 2.41 log₁₀CFU/ml for <it>agr </it>dysfunctional MRSA (p = 0.0007).</p> <p>Conclusions</p> <p>Dysfunction in <it>agr </it>was less common among CA-MRSA vs. HA-MRSA. <it>agr </it>dysfunction demonstrated an impact on vancomycin bactericidal activity and pharmacodynamics against a high initial inoculum of CA-MRSA and HA-MRSA, which may have implications for optimal antimicrobial therapy against persistent, difficult to treat MRSA infections.</p

Evaluation of Fourier transform infrared spectroscopy for the rapid identification of glycopeptide-intermediate Staphylococcus aureus

Objectives To evaluate Fourier transform infrared (FTIR) spectroscopy as a rapid method for distinguishing glycopeptide-intermediate Staphylococcus aureus (GISA) from glycopeptide-susceptible methicillin-resistant S. aureus (MRSA) and to compare three data analysis methods. Methods First-derivative normalized spectra of dried films of bacterial growth on Que-Bact® Universal Medium No. 2 were examined by singular value decomposition to identify key spectral regions. Region selection was analysed by principal component analysis (PCA), self-organizing maps (SOMs) and the K-nearest neighbour (KNN) algorithm. The initial data set included 35 GISA (including GISA Mu50 and heterogeneous GISA Mu3) and 25 epidemic MRSA. The regions were then tested using enlarged data sets that included 22 sporadic and 85 additional epidemic MRSA. Results Epidemic MRSA and GISA/hGISA were separated into two distinct clusters on the basis of spectral data from regions 1352-1315 and 1480-1460 cm−1, the former providing 100% correct classification by all three analyses and the latter providing 96.67% correct by PCA, 98.34% by SOM and 100% by KNN. The 1480-1460 cm−1 region was more effective for distinguishing GISA/hGISA from a set combining sporadic and epidemic MRSA, with two GISA/hGISA and four sporadic MRSA misclassified by PCA and SOM (92.69% correct), while the KNN method misclassified three of the four sporadic MRSA (93.90% correct). The addition of 85 other epidemic MRSA this set increased the fraction of correctly classified isolates to 96.41% and 97.01% by PCA, SOM and KNN, respectively. Conclusions As only 6 of 167 isolates were misclassified, FTIR spectroscopy may provide means of rapid and accurate identification of GISA and hGISA among isolates of MRS

Multi-drug resistant Acinetobacter infections in critically injured Canadian forces soldiers

<p>Abstract</p> <p>Background</p> <p>Military members, injured in Afghanistan or Iraq, have returned home with multi-drug resistant <it>Acinetobacter baumannii </it>infections. The source of these infections is unknown.</p> <p>Methods</p> <p>Retrospective study of all Canadian soldiers who were injured in Afghanistan and who required mechanical ventilation from January 1 2006 to September 1 2006. Patients who developed <it>A. baumannii </it>ventilator associated pneumonia (VAP) were identified. All <it>A. baumannii </it>isolates were retrieved for study patients and compared with <it>A. baumannii </it>isolates from environmental sources from the Kandahar military hospital using pulsed-field gel electrophoresis (PFGE).</p> <p>Results</p> <p>During the study period, six Canadian Forces (CF) soldiers were injured in Afghanistan, required mechanical ventilation and were repatriated to Canadian hospitals. Four of these patients developed <it>A. baumannii </it>VAP. <it>A. baumannii </it>was also isolated from one environmental source in Kandahar – a ventilator air intake filter. Patient isolates were genetically indistinguishable from each other and from the isolates cultured from the ventilator filter. These isolates were resistant to numerous classes of antimicrobials including the carbapenems.</p> <p>Conclusion</p> <p>These results suggest that the source of <it>A. baumannii </it>infection for these four patients was an environmental source in the military field hospital in Kandahar. A causal linkage, however, was not established with the ventilator. This study suggests that infection control efforts and further research should be focused on the military field hospital environment to prevent further multi-drug resistant <it>A. baumannii </it>infections in injured soldiers.</p

Livestock-associated Methicillin-Resistant Staphylococcus aureus Sequence Type 398 in Humans, Canada

Recent emergence of infections resulting from this strain is of public health concern

Hypervirulent Clostridium difficile Strains in Hospitalized Patients, Canada1

To determine the incidence rate of infections with North American pulsed-field types 7 and 8 (NAP7/NAP8) strains of Clostrodium difficile, ribotype 078, and toxinotype V strains, we examined data collected for the Canadian Nosocomial Infections Surveillance Program (CNISP) CDI surveillance project during 2004–2008. Incidence of human infections increased from 0.5% in 2004/2005 to 1.6% in 2008

Nursing Home Residents and Enterobacteriaceae Resistant to Third-Generation Cephalosporins

Limited data identify the risk factors for infection with Enterobacteriaceae resistant to third-generation cephalosporins among residents of long-term-care facilities. Using a nested case-control study design, nursing home residents with clinical isolates of Enterobacteriaceae resistant to third-generation cephalosporins were compared to residents with isolates of Enterobacteriaceae susceptible to third-generation cephalosporins. Data were collected on antimicrobial drug exposure 10 weeks before detection of the isolates, facility-level demographics, hygiene facilities, and staffing levels. Logistic regression models were built to adjust for confounding variables. Twenty-seven case-residents were identified and compared to 85 controls. Exposure to any cephalosporin (adjusted odds ratio [OR] 4.0, 95% confidence interval [CI] 1.2 to13.6) and log percentage of residents using gastrostomy tubes within the nursing home (adjusted OR 3.9, 95% CI 1.3 to 12.0) were associated with having a clinical isolate resistant to third-generation cephalosporins

When should a diagnosis of influenza be considered in adults requiring intensive care unit admission? Results of population-based active surveillance in Toronto

INTRODUCTION: There is a paucity of data about the clinical characteristics that help identify patients at high risk of influenza infection upon ICU admission. We aimed to identify predictors of influenza infection in patients admitted to ICUs during the 2007/2008 and 2008/2009 influenza seasons and the second wave of the 2009 H1N1 influenza pandemic as well as to identify populations with increased likelihood of seasonal and pandemic 2009 influenza (pH1N1) infection. METHODS: Six Toronto acute care hospitals participated in active surveillance for laboratory-confirmed influenza requiring ICU admission during periods of influenza activity from 2007 to 2009. Nasopharyngeal swabs were obtained from patients who presented to our hospitals with acute respiratory or cardiac illness or febrile illness without a clear nonrespiratory aetiology. Predictors of influenza were assessed by multivariable logistic regression analysis and the likelihood of influenza in different populations was calculated. RESULTS: In 5,482 patients, 126 (2.3%) were found to have influenza. Admission temperature ≥38°C (odds ratio (OR) 4.7 for pH1N1, 2.3 for seasonal influenza) and admission diagnosis of pneumonia or respiratory infection (OR 7.3 for pH1N1, 4.2 for seasonal influenza) were independent predictors for influenza. During the peak weeks of influenza seasons, 17% of afebrile patients and 27% of febrile patients with pneumonia or respiratory infection had influenza. During the second wave of the 2009 pandemic, 26% of afebrile patients and 70% of febrile patients with pneumonia or respiratory infection had influenza. CONCLUSIONS: The findings of our study may assist clinicians in decision making regarding optimal management of adult patients admitted to ICUs during future influenza seasons. Influenza testing, empiric antiviral therapy and empiric infection control precautions should be considered in those patients who are admitted during influenza season with a diagnosis of pneumonia or respiratory infection and are either febrile or admitted during weeks of peak influenza activity

Characterisation and Carriage Ratio of Clostridium difficile Strains Isolated from a Community-Dwelling Elderly Population in the United Kingdom

Background Community-associated Clostridium difficile infection (CDI) appears to be an increasing problem. Reported carriage rates by C.difficile are debatable with suggestions that primary asymptomatic carriage is associated with decreased risk of subsequent diarrhoea. However, knowledge of potential reservoirs and intestinal carriage rates in the community, particularly in the elderly, the most susceptible group, is limited. We have determined the presence of C.difficile in the faeces of a healthy elderly cohort living outside of long-term care facilities (LCFs) in the United Kingdom. Methods Faecal samples from 149 community-based healthy elderly volunteers (median age 81 years) were screened for C.difficile using direct (Brazier's CCEY) and enrichment (Cooked Meat broth) culture methods and a glutamate dehydrogenase (GDH) immunoassay. Isolates were PCR-ribotyped and analysed for toxin production and the presence of toxin genes. Results Of 149 faecal samples submitted, six (4%) were found to contain C.difficile. One particular sample was positive by both the GDH immunoassay and direct culture, and concurrently produced two distinct strain types: one toxigenic and the other non-toxigenic. The other five samples were only positive by enrichment culture method. Overall, four C.difficile isolates were non-toxigenic (PCR-ribotypes 009, 026 (n = 2) and 039), while three were toxigenic (PCR-ribotypes 003, 005 and 106). All individuals who had a positive culture were symptom-free and none of them had a history of CDI and/or antibiotics use in the 3 month period preceding recruitment. Conclusions To our knowledge, this is the first study of the presence of C.difficile in healthy elderly community-dwelling individuals residing outside of LCFs. The observed carriage rate is lower than that reported for individuals in LCFs and interestingly no individual carried the common epidemic strain PCR-ribotype 027 (NAP1/BI). Further follow-up of asymptomatic carriers in the community, is required to evaluate host susceptibility to CDI and identify dynamic changes in the host and microbial environment that are associated with pathogenicity