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.

The emerging crisis in antibiotic resistance and concern that we now sit on the precipice of a post-antibiotic era have given rise to advocacy at the highest levels for widespread adoption of programmes that promote judicious use of antibiotics. These antibiotic stewardship programmes, which seek to optimize antibiotic choice when clinically indicated and discourage antibiotic use when clinically unnecessary, are being implemented in an increasing number of acute care facilities, but their adoption has been slower in nursing homes. The antibiotic prescribing process in nursing homes is fundamentally different from that observed in hospital and clinic settings, with formidable challenges to implementation of effective antibiotic stewardship. Nevertheless, an emerging body of research points towards ways to improve antibiotic prescribing practices in nursing homes. This review summarizes the findings of this research and presents ways in which antibiotic stewardship can be implemented and optimized in the nursing home setting.

Proton pump inhibitors (PPIs) have been identified as a risk factor for Clostridium difficile-associated diarrhea (CDAD), though the mechanism is unclear because gastric acid does not kill C. difficile spores. We hypothesized that the vegetative form of C. difficile, which is killed by acid, could contribute to disease pathogenesis if it survives in room air and in gastric contents with elevated pH. We compared the numbers of C. difficile spores and vegetative cells in stools of patients prior to and during the treatment of CDAD. We assessed the survival of vegetative cells on moist or dry surfaces in room air versus anaerobic conditions and in human gastric contents, in pH-adjusted gastric contents, and in gastric contents from individuals receiving PPI therapy. Stool samples obtained from patients prior to the initiation of antibiotic treatment for C. difficile contained ϳ10-fold more vegetative cells than spores. On dry surfaces, vegetative C. difficile cells died rapidly, whereas they remained viable for up to 6 h on moist surfaces in room air. Vegetative C. difficile cells had only marginal survival in gastric contents at low pH; adjustment to a pH of >5 resulted in survival similar to that in the phosphate-buffered saline control. The survival of vegetative C. difficile in gastric contents obtained from patients receiving PPIs was also increased at a pH of >5. The ability of the vegetative form of C. difficile to survive on moist surfaces and in gastric contents with an elevated pH suggests a potential mechanism by which PPI therapy could increase the risk of acquiring C. difficile.

Design We introduced a long-term care facility (LTCF) Infectious Disease (ID) consult service (LID) that provides on-site consultations to residents of a VA LTCF. We determined the impact of the LID service on antimicrobial use and Clostridium difficile infections at the LTCF. Setting A 160-bed Veterans Affairs (VA) LTCF. Methods Systemic antimicrobial use and the rate of positive C. difficile tests at the LTCF were compared for 36 months before and 18 months after the initiation of the ID consultation service using segmented regression analysis of an interrupted time-series. Results In contrast to the pre-intervention period, total systemic antibiotic administration decreased by 30% (P <.001) with a significant reduction in both oral (32%; P<.001) and intravenous agents (25%; P =.008). The greatest reductions were seen for tetracyclines (64%, P <.001), clindamycin (61%; P <.001), sulfamethoxazole/trimethoprim (38%; P <.001), fluoroquinolones (38%; P <.001) and beta-lactam/beta-lactamase inhibitor combinations (28%; P <.001). Rates of change for positive C. difficile tests at the LTCF declined in the post- vs. preintervention periods (P = .04). Conclusions Implementation of a LTCF ID service led to a significant reduction in total antimicrobial use. Bringing providers with infectious disease expertise to the LTCF represents a new and effective means to achieve antimicrobial stewardship.

Synopsis Urinary tract infections (UTIs) are a significant cause of morbidity among older adults; however, antibiotic prescriptions for clinically suspected UTIs are often inappropriate. Healthcare providers frequently struggle to differentiate UTI from asymptomatic bacteriuria, particularly in patients presenting with nonspecific symptoms. Patients with baseline cognitive impairments that limit history-taking can be particularly challenging. Here, we review the epidemiology and pathogenesis of UTI in older adults. We also discuss an approach to the diagnosis and treatment of UTIs, focusing on recognizing patients who would likely benefit from antibiotic treatment and on identifying patients for whom empiric antibiotic therapy should not be given.

In an observational study with a limited number of subjects, a majority of patients with C. difficile-associated disease responded to therapy with metronidazole or vancomycin. Failure with metronidazole treatment may be attributable to a slower and less consistent microbiological response than that with oral vancomycin treatment.

Background Clostridium difficile is an anaerobic, spore-forming bacterium that is the most common cause of healthcare-associated diarrhea in developed countries. A significant proportion of patients receiving oral vancomycin or metronidazole for treatment of Clostridium difficile infection (CDI) develop recurrences. However, the period of vulnerability to re-establishment of colonization by C. difficile after therapy is not well defined.Principal FindingsIn a prospective study of CDI patients, we demonstrated that most vancomycin-treated patients maintained inhibitory concentrations of vancomycin in stool for 4 to 5 days after therapy, whereas metronidazole was only detectable during therapy. From the time of elimination of the antibiotics to 14 to 21 days after therapy, a majority of stool suspensions supported growth of C. difficile and deep 16S rRNA sequencing demonstrated persistent marked alteration of the indigenous microbiota. By 21 to 28 days after completion of CDI treatment, a majority of stool suspensions inhibited growth of C. difficile and there was evidence of some recovery of the microbiota.ConclusionsThese data demonstrate that there is a vulnerable period for re-establishment of C. difficile colonization after CDI treatment that begins within a few days after discontinuation of treatment and extends for about 3 weeks in most patients.

BackgroundThe intestinal microbiota protect the host against enteric pathogens through a defense mechanism termed colonization resistance. Antibiotics excreted into the intestinal tract may disrupt colonization resistance and alter normal metabolic functions of the microbiota. We used a mouse model to test the hypothesis that alterations in levels of bacterial metabolites in fecal specimens could provide useful biomarkers indicating disrupted or intact colonization resistance after antibiotic treatment.MethodsTo assess in vivo colonization resistance, mice were challenged with oral vancomycin-resistant Enterococcus or Clostridium difficile spores at varying time points after treatment with the lincosamide antibiotic clindamycin. For concurrent groups of antibiotic-treated mice, stool samples were analyzed using quantitative real-time polymerase chain reaction to assess changes in the microbiota and using non-targeted metabolic profiling. To assess whether the findings were applicable to another antibiotic class that suppresses intestinal anaerobes, similar experiments were conducted with piperacillin/tazobactam.ResultsColonization resistance began to recover within 5 days and was intact by 12 days after clindamycin treatment, coinciding with the recovery bacteria from the families Lachnospiraceae and Ruminococcaceae, both part of the phylum Firmicutes. Clindamycin treatment caused marked changes in metabolites present in fecal specimens. Of 484 compounds analyzed, 146 (30%) exhibited a significant increase or decrease in concentration during clindamycin treatment followed by recovery to baseline that coincided with restoration of in vivo colonization resistance. Identified as potential biomarkers of colonization resistance, these compounds included intermediates in carbohydrate or protein metabolism that increased (pentitols, gamma-glutamyl amino acids and inositol metabolites) or decreased (pentoses, dipeptides) with clindamycin treatment. Piperacillin/tazobactam treatment caused similar alterations in the intestinal microbiota and fecal metabolites.ConclusionsRecovery of colonization resistance after antibiotic treatment coincided with restoration of several fecal bacterial metabolites. These metabolites could provide useful biomarkers indicating intact or disrupted colonization resistance during and after antibiotic treatment.