Mark A. Miller

Clostridium difficile infection (CDI) is the leading infectious cause of nosocomial diarrhea. Hospitalized patients are at increased risk of developing CDI because they are exposed to C. difficile spores through contact with the hospital environment and often receive antibiotics and other medications that can disrupt the integrity of the indigenous intestinal microbiota and impair colonization resistance. Using whole metagenome shotgun sequencing, we examined the diversity and composition of the fecal microbiota in a prospective cohort study of 98 hospitalized patients. Four patients had asymptomatic C. difficile colonization, and four patients developed CDI. We observed dramatic shifts in the structure of the gut microbiota during hospitalization. In contrast to CDI cases, asymptomatic patients exhibited elevated relative abundance of potentially protective bacterial taxa in their gut at the onset of C. difficile colonization. Use of laxatives was associated with significant reductions in the relative abundance of Clostridium and Eubacterium; species within these genera have previously been shown to enhance resistance to CDI via the production of secondary bile acids. Cephalosporin and fluoroquinolone exposure decreased the frequency of Clostridiales Family XI Incertae Sedis, a bacterial family that has been previously associated with decreased CDI risk. This study underscores the detrimental impact of antibiotics as well as other medications, particularly laxatives, on the intestinal microbiota and suggests that co-colonization with key bacterial taxa may prevent C. difficile overgrowth or the transition from asymptomatic C. difficile colonization to CDI.

Objective: To determine whether relaxing vancomycin-resistant enterococci (VRE) precautions results in an increase in the incidence of invasive VRE infections over time.Design: Retrospective analysis of a microbiology database before and after relaxation of VRE screening and isolation precautions.Setting: Urban tertiary care teaching hospital in Montreal, Canada.Participants.: All hospitalized and emergency room patients over a 13-year period from January 1, 2000, to March 31, 2013.Methods: We assessed the results of all microbiology cultures for the presence of VRE as well as the results of all polymerase chain reaction assays forvanAandvanBduring the study period. Applying criteria for 4 clinical situations (bacteremia, definite infection, possible infection, and colonization with VRE), we analyzed the effects of relaxed VRE screening and isolation precautions on the incidence of each of these outcomes over the time preceding and following this change.Results: When VRE screening and isolation precautions were relaxed, a marked rise in VRE colonization was observed, with a lesser but definite rise in the 3 other outcomes. Despite this initial rise in all measures, all incidences other than colonization plateaued during the 34 months of follow-up.Conclusions: Relaxation of VRE screening and isolation precautions was associated with an immediate increase in colonization and infection incidence. Despite increasing colonization, infection outcomes remained infrequent and stable, suggesting a finite number of susceptible hosts at risk. Relaxation of VRE protocols may not lead to increasing infection incidence in a hospital setting, advocating that cost effectiveness exercises, with targeted screening and isolation precautions, are crucial.

Clostridium difficile infection (CDI) continues to be a frequent and potentially severe infection. There is currently no validated clinical tool for use at the time of CDI diagnosis to categorize patients in order to predict response to therapy.

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.

To the Editor—The letter by Pillai et al [1] is an interesting addition to the current knowledge of the epidemiology of Clostridium difficile infection (CDI) in Canada. Their data are actually not very different from the data that we recently published in our Canadian survey [2]; it merely represents a different time period being analyzed.

Clostridium difficile infection (CDI) has become an increasingly important healthcare-associated complication in many countries. CDI outbreaks, a new 'hypervirulent' form and increased worldwide rates have underscored four urgent unmet needs for this disease: i) effective prevention of CDI; ii) therapies to produce faster resolution of CDI symptoms; iii) therapies to treat severe CDI more effectively and reduce its mortality; and iv) therapies to reduce the CDI recurrence rate following treatment. Fidaxomicin, a new macrocyclic antibiotic, has demonstrated potent in vitro activity against C. difficile with limited or no activity against normal fecal flora. It is minimally absorbed from the intestinal tract, even in the presence of intestinal inflammation. When tested against oral vancomycin in clinical studies of CDI therapy, it has equivalent efficacy for curing CDI at end of treatment and a comparable safety profile to that agent. However, fidaxomicin therapy of CDI is associated with significantly fewer CDI recurrences in the 28 days following treatment. Symptom resolution is also slightly quicker in some CDI patients. Additional fecal flora analysis in the CDI trials showed that fewer individuals developed intestinal colonization with vancomycin-resistant enterococci (VRE) among the fidaxomicin-treated group. This new molecule, which has just completed two large Phase III multicenter studies, successfully addresses two of the four urgent and unmet needs for dealing with CDI. Fidaxomicin is as effective and as safe as vancomycin therapy for treating CDI but is associated with far fewer recurrences post-treatment and a decreased risk of VRE acquisition. Fidaxomicin is a potential new therapy for CDI which has the capacity to substantially decrease post-treatment recurrences and is as safe and well-tolerated as standard vancomycin treatment.

Background. C. difficile infection (CDI) has become an important and frequent nosocomial infection, often resulting in severe morbidity or death. Sever

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.

The incidence of Clostridium difficile-associated disease (CDAD) and its serious complications (including colectomy and death) have been increasing w