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 g/mL, with a maximum MIC for inhibition of 90 of organisms (MIC90) of 0.5 g/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 g/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 g/mL and an MIC90 of 8 g/mL. Changes in inoculum size (102-105 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. © 2012 The Author.