[Show abstract][Hide abstract] ABSTRACT: From September 2010 to December 2011, twenty-six KPC-3-producing Enterobacter cloacae were identified from sixteen patients at a single hospital. Analyses revealed the blaKPC to be localized on multiple plasmids in a diverse non-clonal E. cloacae genetic background. These findings highlight the potential complexity of a KPC outbreak at a single hospital.
Journal of clinical microbiology 05/2013; · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fidaxomicin causes less disruption of anaerobic microbiota during treatment of Clostridium difficile infection (CDI) than vancomycin and has activity against many vancomycin-resistant enterococci (VRE). In conjunction with a multicenter randomized trial of fidaxomicin versus vancomycin for CDI treatment, we tested the hypothesis that fidaxomicin promotes VRE and Candida species colonization less than vancomycin. Stool was cultured for VRE and Candida species before and after therapy. For patients with negative pretreatment cultures, the incidence of VRE and Candida species acquisition was compared. For those with preexisting VRE, the change in concentration during treatment was compared. The susceptibility of VRE isolates to fidaxomicin was assessed. Of 301 patients, 247 (82%) had negative VRE cultures and 252 (84%) had negative Candida species cultures before treatment. In comparison with vancomycin-treated patients, fidaxomicin-treated patients had reduced acquisition of VRE (7% vs 31%, respectively; P < .001) and Candida species (19% vs 29%, respectively; P = .03). For patients with preexisting VRE, the mean concentration decreased significantly in the fidaxomicin group (5.9 vs 3.8 log(10) VRE/g stool; P = .01) but not the vancomycin group (5.3 vs 4.2 log(10) VRE/g stool; P = .20). Most VRE isolates recovered after fidaxomicin treatment had elevated fidaxomicin minimum inhibitory concentrations (MICs; MIC(90), 256 µg/mL), and subpopulations of VRE with elevated fidaxomicin MICs were common before therapy. Fidaxomicin was less likely than vancomycin to promote acquisition of VRE and Candida species during CDI treatment. However, selection of preexisting subpopulations of VRE with elevated fidaxomicin MICs was common during fidaxomicin therapy.
[Show abstract][Hide abstract] ABSTRACT: Nonsevere Clostridium difficile infection (CDI) and severe CDI, which carries a higher risk than nonsevere CDI for treatment failure and CDI recurrence, are difficult to distinguish at the time of diagnosis. To investigate the prognostic value of 3 markers of severe CDI suggested by recent guidelines (fever, leukocytosis, and renal failure), we used the database of 2 randomized controlled trials, which contained information for 1105 patients with CDI. Leukocytosis (risk ratio [RR], 2.29; 95% confidence interval [CI], 1.63-3.21) and renal failure (RR, 2.52; 95% CI, 1.82-3.50) were associated with treatment failure. Fever, although associated with treatment failure (RR, 2.45; 95% CI, 1.07-5.61), was rare. Renal failure was the only significant predictor of recurrence (RR, 1.45; 95% CI, 1.05-2.02). Different timing of measurements of leukocyte count and serum creatinine level around the CDI diagnosis led to a different severity classification in many cases. In conclusion, both leukocytosis and renal failure are useful predictors, although timing of measurement is important.
[Show abstract][Hide abstract] ABSTRACT: We tested the activities of rifampin (RIF) and rifaximin (RFX) against 180 Clostridium difficile clinical isolates selected from Canadian and Italian culture collections. MICs were determined by CLSI agar dilution for both drugs and by Etest for RIF. Sixteen of 85 Italian isolates (18.8%) showed high-level resistance to both rifamycins (MICs, >16 μg/ml), compared to 2 of 95 (2.1%) Canadian isolates. Two new rpoB mutations were identified in rifamycin-resistant isolates. RIF susceptibility by Etest correlated completely with susceptibility to both rifamycins determined by agar dilution.
Journal of clinical microbiology 12/2011; 49(12):4319-21. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clostridium difficile is a common cause of infectious diarrhea in hospitalized patients. A severe and increased incidence of C. difficile infection (CDI) is associated predominantly with the NAP1 strain; however, the existence of other severe-disease-associated (SDA) strains and the extensive genetic diversity across C. difficile complicate reliable detection and diagnosis. Comparative genome analysis of 14 sequenced genomes, including those of a subset of NAP1 isolates, allowed the assessment of genetic diversity within and between strain types to identify DNA markers that are associated with severe disease. Comparative genome analysis of 14 isolates, including five publicly available strains, revealed that C. difficile has a core genome of 3.4 Mb, comprising ∼ 3,000 genes. Analysis of the core genome identified candidate DNA markers that were subsequently evaluated using a multistrain panel of 177 isolates, representing more than 50 pulsovars and 8 toxinotypes. A subset of 117 isolates from the panel had associated patient data that allowed assessment of an association between the DNA markers and severe CDI. We identified 20 candidate DNA markers for species-wide detection and 10,683 single nucleotide polymorphisms (SNPs) associated with the predominant SDA strain (NAP1). A species-wide detection candidate marker, the sspA gene, was found to be the same across 177 sequenced isolates and lacked significant similarity to those of other species. Candidate SNPs in genes CD1269 and CD1265 were found to associate more closely with disease severity than currently used diagnostic markers, as they were also present in the toxin A-negative and B-positive (A-B+) strain types. The genetic markers identified illustrate the potential of comparative genomics for the discovery of diagnostic DNA-based targets that are species specific or associated with multiple SDA strains.
Journal of clinical microbiology 06/2011; 49(6):2230-8. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We compared PCR to conventional culture for the detection of vancomycin-resistant enterococci (VRE) in 30,835 rectal samples over a 3-year period. The positive and negative predictive values of vanB PCR were 1.42% and 99.9%, respectively. A positive vanB result by PCR is poorly predictive and necessitates culture for differentiation of VRE-positive and -negative individuals.
Journal of clinical microbiology 10/2009; 47(12):4136-7. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clostridium difficile-associated disease (CDAD) has increased in frequency and severity throughout North America and Europe over the last 5 years, largely due to the emergence of the NAP1 epidemic strain. This transformation of a formerly mild disease into one that can cause severe morbidity and mortality within a few days has challenged our entire approach to this serious infection. Institutions require accurate and rapid diagnostics for early detection of cases and possible outbreaks in order to initiate specific therapy and implement effective infection control. The optimal hand hygiene techniques, barrier methods and environmental cleaning practices that would diminish transmission remain uncertain. Clinicians need reliable research that can pinpoint the most important factors determining severity of disease and relapse. Epidemiologic and molecular analyses are vital in order to understand the local and international transmission of this disease, as well as its recent change in pathogenicity. As well, further examination of this infection is crucial in order to find effective prophylactic maneuvers and optimal therapies. This review discusses the changing epidemiology of CDAD across North America and internationally, as well as the common diagnostic methods and molecular typing tools for this pathogen. Finally, the current evidence supporting conventional, novel, and non-antimicrobial preventative and therapeutic options is examined.
[Show abstract][Hide abstract] ABSTRACT: Enterococcus gallinarum N04-0414 (MIC for vancomycin, 256 microg/ml) harbored a vanD-type vancomycin resistance operon as well as the intrinsic vanC1 operon. The D-Ala:D-Ala ligase 2 gene (ddl2) was not present in the strain, though it is found downstream of the vanS gene from the vanC operon in E. gallinarum ATCC 49573 and 19 other E. gallinarum strains tested.
Antimicrobial Agents and Chemotherapy 04/2006; 50(3):1067-70. · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In March 2003, several hospitals in Quebec, Canada, noted a marked increase in the incidence of Clostridium difficile-associated diarrhea.
In 2004 we conducted a prospective study at 12 Quebec hospitals to determine the incidence of nosocomial C. difficile-associated diarrhea and its complications and a case-control study to identify risk factors for the disease. Isolates of C. difficile were typed by pulsed-field gel electrophoresis and analyzed for binary toxin genes and partial deletions in the toxin A and B repressor gene tcdC. Antimicrobial susceptibility was evaluated in a subgroup of isolates.
A total of 1703 patients with 1719 episodes of nosocomial C. difficile-associated diarrhea were identified. The incidence was 22.5 per 1000 admissions. The 30-day attributable mortality rate was 6.9 percent. Case patients were more likely than matched controls to have received fluoroquinolones (odds ratio, 3.9; 95 percent confidence interval, 2.3 to 6.6) or cephalosporins (odds ratio, 3.8; 95 percent confidence interval, 2.2 to 6.6). A predominant strain, resistant to fluoroquinolones, was found in 129 of 157 isolates (82.2 percent), and the binary toxin genes and partial deletions in the tcdC gene were present in 132 isolates (84.1 percent).
A strain of C. difficile that was resistant to fluoroquinolones and had binary toxin and a partial deletion of the tcdC gene was responsible for this outbreak of C. difficile-associated diarrhea. Exposure to fluoroquinolones or cephalosporins was a risk factor.
New England Journal of Medicine 01/2006; 353(23):2442-9. · 51.66 Impact Factor