Effectiveness of probiotics in reducing the incidence of Clostridium difficile-associated diarrhea in elderly patients: a systematic review

Background Clostridium difficile bacteria are a leading cause of infectious diarrhea. This is an anaerobic, gram-positive and spore-forming rod responsible for significant morbidity and mortality, especially among elderly hospitalized patients. Standard management of C. difficile-associated diarrhea (CDAD) consists of discontinuing a causative antibiotic, correcting fluid-electrolytes imbalance and initiating an antibiotic treatment for CDAD. Alternative approaches for prevention of CDAD include probiotics. This systematic review will provide a comprehensive, unbiased summary of the available research on the effectiveness of probiotics in decreasing the incidence of infectious diarrhea in elderly hospitalized patients. Objectives To conduct a systematic review to determine the best available evidence related to the effectiveness of probiotics in the prevention of CDAD in elderly hospitalized patients. The review question was: are probiotics effective in decreasing the incidence of CDAD in elderly hospitalized patients? Inclusion criteria Types of participants The current review included studies of participants who were aged 60 years and more and who were residents of acute- and post-acute care facilities undergoing or planning to undergo antibiotic treatment for the management of any infectious conditions, except CDAD. Types of intervention(s) The current review included studies that evaluated the effectiveness of probiotics for prevention of CDAD in elderly hospitalized patients in acute- and post-acute care settings compared to usual care. Outcomes The current review included studies examining the following outcome measures: incidence or relapse of CDAD. Cases of CDAD were defined by presence of diarrhea and verified by positive results for stool enzyme immunoassay for toxins A and B. Types of studies The current review included only experimental study designs including randomized controlled trials. Search strategy The search strategy included studies published in English between 1978, when the first case of CDAD was reported, and 2015. Assessment of methodological quality Papers selected for retrieval were assessed by two independent reviewers for methodological quality prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute (JBI). Data extraction Data were extracted from papers included in the review using the standardized data extraction tool from the JBI Meta-Analysis of Statistics Assessment and Review Instrument. The data extracted included specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. Data synthesis Quantitative data were pooled using statistical meta-analysis. Effect sizes were expressed as odds ratios, and their 95% confidence intervals were calculated to determine if probiotic treatment was superior to placebo in reducing CDAD incidence. Heterogeneity was assessed using the standard I2 statistic. Results Five studies were included in the review. The individual study results were conflicting, including non-significant results for four studies and statistically significant results in one that demonstrated fewer cases of CDAD among patients receiving probiotics compared to placebo. The meta-analysis finding indicated that there was no statistically significant difference in CDAD incidence in elderly hospitalized patients taking probiotics when compared to a placebo. Conclusion Probiotics were not found to be more effective than placebo for reducing CDAD incidence in elderly hospitalized patients. However, studies that demonstrate improved outcomes must be examined to determine future needs for research. Studies varied with regard to the dose, frequency, method of administration (probiotic drinks versus capsule), length of administration and the number of strains of bacteria administered. Further studies are needed to evaluate the effectiveness of probiotics for CDAD prevention in this population. Clinical trials with evidence-based administration methods and meta-analyses that pool the results of studies with congruent methodologies are needed to enable conclusions to be drawn on the effectiveness of probiotic administration for CDAD prevention.