Perils and pitfalls of probiotic quasi-experimental studies for primary prevention of Clostridioides difficile infection: A review of the evidence

Abstract

Primary prevention of Clostridioides (Clostridium) difficile infections (CDI) is an important but challenging infection control goal for hospitals and health care facilities. Enhanced infection control protocols have reduced CDI rates, but the problem persists and administration of probiotics to patients at risk could be very useful if shown to be safe and effective. Randomized controlled trials are largely impractical for primary prevention CDI trials due to large required study sizes and quasi-experimental studies are becoming more frequent as a method to assess this problem. Our goal is to review the published quasi-experimental studies adding probiotics to their infection control protocols to reduce CDI and determine the strengths and limitations for this type of study design. The literature was searched using PubMed, Google Scholar, Medline and Cochrane Databases and gastrointestinal meeting abstracts from January 2000 to January 2020 for quasi-experimental intervention studies testing various probiotics for the primary prevention of CDI. We found 28 studies with 7 different types of probiotics (10 studies implementing a hospital-wide intervention, 6 studies targeting 1-3 wards, and 12 studies on either sustainability, cost-effectiveness or subgroup analysis). Some probiotics demonstrated a significant reduction in CDI rates; all four of the probiotic types given only on specific wards and 3 of the 4 probiotics given facility-wide. However, this type of study design was influenced by numerous factors which must be carefully accounted for in the analysis. Some probiotics may be an effective addition to infection control protocols to prevent C. difficile infections, but careful study design considerations are needed.