Susceptibilities of clinical Clostridium difficile isolates to antimicrobials: a systematic review and meta-analysis of studies since 1970

International audienceOBJECTIVES: Although exposure to antibiotics can cause Clostridium difficile infection, certain antibiotics are used to treat C.~difficile. Measurements of antimicrobial C.~difficile activity could help to identify antibiotic risk and emergent resistance. Here, we describe publication patterns relating to C.~difficile susceptibilities and estimate minimum inhibitory concentrations (MIC) for antibiotic classes in the published literature between January 1970 and June 2014. METHODS: We queried PUBMED and EMBASE for studies reporting antibiotic C.~difficile MIC in English or French. We used mixed-effects models to obtain pooled estimates of antibiotic class median MIC (MIC50), 90th percentile of MIC (MIC90), and MIC90:MIC50 ratio. RESULTS: Our search identified 182 articles that met our inclusion criteria, of which 27 were retained for meta-analysis. Aminoglycosides (MIC50 120~mg/L, 95% CI 62-250), 3rd (MIC50 75~mg/L, 95% CI 39-130) and 2nd generation cephalosporins (MIC50 64~mg/L, 95% CI 27-140) had the least C.~difficile activity. Rifamycins (MIC50 0.034~mg/L, 95% CI 0.012-0.099) and tetracyclines (MIC50 0.29~mg/L, 95% CI 0.054-1.7) had the highest level of activity. The activity of 3rd generation cephalosporins was more than three times lower than that of 1st generation agents (MIC50 19~mg/L, 95% CI 7.0-54). Time-trends in MIC50 were increasing for carbapenems (70% increase per 10~years) while decreasing for tetracyclines (51% decrease per 10~years). CONCLUSIONS: We found a 3500-fold variation in antibiotic C.~difficile MIC50, with aminoglycosides as the least active agents and rifamycins as the most active. Further research is needed to determine how in~vitro measures can help assess patient C.~difficile risk and guide antimicrobial stewardship