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BackgroundOral vancomycin (125 mg qid) is recommended as treatment of severe Clostridium difficile infection (CDI). Higher doses (250 or 500 mg qid) are sometimes recommended for patients with very severe CDI, without supporting clinical evidence. We wished to determine to what extent faecal levels of vancomycin vary according to diarrhoea severity and dosage, and whether it is rational to administer high-dose vancomycin to selected patients.MethodsWe recruited hospitalized adults suspected to have CDI for whom oral vancomycin (125, 250 or 500 mg qid) had been initiated. Faeces were collected up to 3 times/day and levels were measured with the AxSYM fluorescence polarization immunoassay.ResultsFifteen patients (9 with confirmed CDI) were treated with oral vancomycin. Patients with ≥4 stools daily presented lower faecal vancomycin levels than those with a lower frequency. Higher doses of oral vancomycin (250 mg or 500 mg qid) led to consistently higher faecal levels (> 2000 mg/L), which were 3 orders of magnitude higher than the MIC90 of vancomycin against C. difficile. One patient receiving 125 mg qid had levels below 50 mg/L during the first day of treatment.ConclusionsFaecal levels of vancomycin are proportional to the dosage administered and, even in patients with increased stool frequency, much higher than the MIC90. Patients given the standard 125 mg qid dosage might have low faecal levels during the first day of treatment. A loading dose of 250 mg or 500 mg qid during the first 24-48 hours followed by the standard dosage should be evaluated in larger studies, since it might be less disruptive to the colonic flora and save unnecessary costs.

is an environmental bacterium that is commonly associated with outbreaks in neonatal intensive care units (NICUs). Investigations of outbreaks require efficient recovery and typing of clinical and environmental isolates. In this study, we investigated how the use of next-generation sequencing applications, such as bacterial whole-genome sequencing (WGS) and bacterial community profiling, could improve outbreak investigations. Phylogenomic links and potential antibiotic resistance genes and plasmids in isolates were investigated using WGS, while bacterial communities and relative abundances of in environmental samples were assessed using sequencing of bacterial phylogenetic marker genes (16S rRNA and genes). Typing results obtained using WGS for the 10 isolates recovered during a NICU outbreak investigation were highly consistent with those obtained using pulsed-field gel electrophoresis (PFGE), the current standard typing method for this bacterium. WGS also allowed the identification of genes associated with antibiotic resistance in all isolates, while no plasmids were detected. Sequencing of the 16S rRNA and genes both showed greater relative abundances of at environmental sampling sites that were in close contact with infected babies. Much lower relative abundances of were observed following disinfection of a room, indicating that the protocol used was efficient. Variations in the bacterial community composition and structure following room disinfection and among sampling sites were also identified through 16S rRNA gene sequencing. Together, results from this study highlight the potential for next-generation sequencing tools to improve and to facilitate outbreak investigations.

OBJECTIVE Central-line-associated bloodstream infections (CLABSI) are an important cause of morbidity and mortality in neonates. We aimed to determine whether intra-abdominal pathologies are an independent risk factor for CLABSI. METHODS We performed a retrospective matched case-control study of infants admitted to the neonatal intensive care units (NICUs) of the Montreal Children's Hospital (Montreal) and the Royal Alexandra Hospital, Edmonton, Canada. CLABSI cases that occurred between April 2009 and March 2014 were identified through local infection control databases. For each case, up to 3 controls were matched (National Healthcare Safety Network [NHSN] birth weight category, chronological age, and central venous catheter (CVC) dwell time at the time of CLABSI onset). Data were analyzed using conditional logistic regression. RESULTS We identified 120 cases and 293 controls. According to a matched univariate analysis, the following variables were significant risk factors for CLABSI: active intra-abdominal pathology (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.8-6.4), abdominal surgery in the prior 7 days (OR, 3.5; 95% CI, 1.0-10.9); male sex (OR, 1.7; 95% CI, 1.1-2.6) and ≥3 heel punctures (OR, 4.0; 95% CI, 1.9-8.3). According to a multivariate matched analysis, intra-abdominal pathology (OR, 5.9; 95% CI, 2.5-14.1), and ≥3 heel punctures (OR, 5.4; 95% CI, 2.4-12.2) remained independent risk factors for CLABSI. CONCLUSION The presence of an active intra-abdominal pathology increased the risk of CLABSI by almost 6-fold. Similar to CLABSI in oncology patients, a subgroup of CLABSI with mucosal barrier injury should be considered for infants in the NICU with active intra-abdominal pathology. Infect Control Hosp Epidemiol 2016;1446-1452.