Background. Asymptomatic fecal carriage of Clostridium difficile is common in patients staying in health care facilities, but the importance of asymptomatic carriers with regard to disease transmission is unclear.Methods. We prospectively examined the prevalence of asymptomatic carriage of epidemic North American pulsed-field gel electrophoresis type 1 and nonepidemic toxigenic C. difficile strains among long-term care patients in the context of an outbreak of C. difficile-associated disease and evaluated the frequency of skin and environmental contamination. Molecular typing was performed by pulsed-field gel electrophoresis. Logistic regression was used to assess factors associated with asymptomatic carriage, and a sensitive and specific prediction rule was developed to identify high-risk patients.Results. Thirty-five (51%) of 68 asymptomatic patients were carriers of toxigenic C. difficile, and 13 (37%) of these patients carried epidemic strains. Compared with noncarriers, asymptomatic carriers had higher percentages of skin (61% vs. 19%;) and environmental contamination (59% vs. 24%; ). Eighty-seven percent P p .001 P p .004 of isolates found in skin samples and 58% of isolates found in environmental samples were identical to concurrent isolates found in stool samples. Spores on the skin of asymptomatic patients were easily transferred to investigators' hands. Previous C. difficile-associated disease ( ) and previous antibiotic use ( ) were associated P ! .001 P p .017 with asymptomatic carriage, and the combination of these 2 variables was predictive of asymptomatic carriage (sensitivity, 77%; specificity, 58%; positive predictive value, 66%; negative predictive value, 70%).Conclusions. Our findings suggest that asymptomatic carriers of epidemic and nonepidemic C. difficile strains have the potential to contribute significantly to disease transmission in long-term care facilities. Clinical factors, such as previous C. difficile-associated disease and recent antibiotic use, may be predictive of asymptomatic carriage.

For treatment of mild to moderate Clostridium difficile-associated disease (CDAD), oral metronidazole has been recommended as the preferred agent, in part due to concern that vancomycin may be more likely to promote colonization by vancomycin-resistant enterococci (VRE). We performed a prospective observational study to examine the effects of oral metronidazole or vancomycin treatment of CDAD on acquisition and concentration of VRE stool colonization. Before, during, and after 90 courses of CDAD therapy, stool samples were cultured for VRE, and the concentrations were quantified. Eighty-seven subjects (97%) had received antibiotics within the past month. For 56 treatment courses in which preexisting VRE colonization was present, metronidazole (n ‫؍‬ 37 courses) and vancomycin (n ‫؍‬ 19 courses), each promoted persistent VRE overgrowth during therapy, and the concentration decreased significantly in both groups by ϳ2 weeks after completion of treatment (P <0.049). For 34 treatment courses in which baseline cultures were negative for VRE, new detection of VRE stool colonization occurred during 3 (14%) of the 22 courses of metronidazole and 1 (8%) of the 12 courses of vancomycin (P ‫؍‬ 1.0). These results demonstrate that both oral metronidazole and oral vancomycin promote the overgrowth of VRE during treatment of CDAD. New CDAD treatments are needed that are less likely to disrupt the intestinal microflora and promote overgrowth of healthcare-associated pathogens.

In a prospective study of 27 patients with Clostridium difficile-associated disease, we found that C. difficile frequently contaminated multiple skin sites, including groin, chest, abdomen, forearms, and hands, and was easily acquired on investigators' hands. Skin contamination often persisted on patients' chest and abdomen after resolution of diarrhea.

Several recent outbreaks of Clostridium difficile-associated disease (CDAD) have been attributed to the emergence of an epidemic strain with increased resistance to fluoroquinolone antibiotics. Some clinical studies have suggested that fluoroquinolones with enhanced antianaerobic activity (i.e., gatifloxacin and moxifloxacin) may have a greater propensity to induce CDAD than ciprofloxacin and levofloxacin do. We examined the effects of subcutaneous fluoroquinolone treatment on in vitro growth of and toxin production by epidemic and nonepidemic C. difficile isolates in cecal contents of mice and evaluated the potential for these agents to inhibit fluoroquinolone-susceptible isolates during treatment. When C. difficile isolates were inoculated into cecal contents collected 2 days after the final antibiotic dose, gatifloxacin and moxifloxacin promoted significantly more growth and toxin production than ciprofloxacin and levofloxacin did. During treatment, gatifloxacin and moxifloxacin inhibited growth of fluoroquinolone-susceptible but not fluoroquinolone-resistant isolates. Ciprofloxacin and levofloxacin promoted growth of C. difficile when administered at higher doses (i.e., 20 times the human dose in mg/kg of body weight), and levofloxacin inhibited growth of fluoroquinolone-susceptible, but not fluoroquinolone-resistant, C. difficile isolates when administered in combination with ceftriaxone. Thus, fluoroquinolones with enhanced antianaerobic activity (i.e., gatifloxacin and moxifloxacin) promoted C. difficile growth to a greater extent than did ciprofloxacin and levofloxacin in this model. However, our findings suggest that fluoroquinolones may exert selective pressure favoring the emergence of epidemic fluoroquinolone-resistant C. difficile strains by inhibiting fluoroquinolone-susceptible but not fluoroquinolone-resistant isolates during treatment and that agents such as levofloxacin or ciprofloxacin can exert such selective pressure when administered in combination with antibiotics that disrupt the anaerobic microflora.