Susceptibilities of clinical Clostridium difficile isolates to antimicrobials: a systematic review and meta-analysis of studies since 1970.
Clin Microbiol Infect. 2017 Jul 24;:
Authors: Khanafer N, Daneman N, Greene T, Simor A, Vanhems P, Samore M, Brown KA
OBJECTIVES: Although exposure to antibiotics can cause C. difficile infection, certain antibiotics are used to treat C. difficile. The measurements of antimicrobial Clostridium difficile activity could help identifying 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 in order to obtain pooled estimates of antibiotic class median MIC (MIC50), 90(th) 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: 120mg/L, 95%CI: 62-250), 3(rd) (MIC50: 75mg/L, 95%CI: 39-130) and 2(nd) generation cephalosporins (MIC50: 64mg/L, 95%CI: 27-140) had the least C. difficile activity. Rifamycins (MIC50: 0.034mg/L, 95%CI: 0.012-0.099) and tetracyclines (MIC50: 0.29mg/L, 95%CI: 0.054-1.7) had the highest level of activity. The activity of 3(rd) generation cephalosporins was more than 3 times lower than 1(st) generation agents (MIC50: 19mg/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.
PMID: 28750918 [PubMed - as supplied by publisher]