title: Antimicrobial activities of fidaxomicin.
abstract: Fidaxomicin is bactericidal against Clostridium difficile. The combined results of 8 in vitro studies of 1323 C. difficile isolates showed the minimum inhibitory concentration (MIC) range of fidaxomicin to be ≤ 0.001-1 μg/mL, with a maximum MIC for inhibition of 90% of organisms (MIC(90)) of 0.5 μg/mL. Isolates from 2 phase III clinical trials demonstrated that fidaxomicin MICs of baseline isolates did not predict clinical cure, failure, or recurrence of C. difficile infections. No resistance to fidaxomicin developed during treatment in either study, although a single strain recovered from a cured patient had an elevated MIC of 16 µg/mL at the time of recurrence. For 135 strains, OP-1118, a major metabolite, had an MIC for inhibition of 50% of organisms of 4 μg/mL and an MIC(90) of 8 μg/mL. Changes in inoculum size (10(2)-10(5) colony-forming units/spot) or cation concentrations of calcium or magnesium appeared to have no effect on fidaxomicin MICs. Fidaxomicin has little or no activity against gram-negative aerobes and anaerobes or yeast.
authors: RM Alden Research Laboratory, Culver City, CA, USA. ejcgmd@aol.com
authors: Ellie J C
authors: EJ
authors: Goldstein
authors: Farah
authors: F
authors: Babakhani
authors: Diane M
authors: DM
authors: Citron
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D016360:Clostridioides difficile / Q000187:drug effects* / Q000302:isolation & purification; D003015:Clostridium Infections / Q000382:microbiology; D004353:Drug Evaluation, Preclinical; D024881:Drug Resistance, Bacterial; D005243:Feces / Q000382:microbiology; D000077732:Fidaxomicin; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D012008:Recurrence; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C561044:OP-1118; D014640:Vancomycin; D000077732:Fidaxomicin