title: In vitro activity and single-step mutational analysis of rifamycin SV tested against enteropathogens associated with traveler's diarrhea and Clostridium difficile.
abstract: Rifamycin SV is a broad-spectrum, poorly absorbed antimicrobial agent that, when coupled with MMX technology, is being targeted for the oral treatment of traveler's diarrhea (TD) and Clostridium difficile-associated disease (CDAD). Rifamycin SV was tested for activity against 911 TD-associated enteropathogens and 30 C. difficile isolates collected from several global surveillance studies. Rifamycin SV demonstrated similar antimicrobial activity levels against the Enterobacteriaceae, with MIC₅₀ values ranging from 32 to 128 μg/ml for all but one strain (an enterotoxigenic Escherichia coli at >512 μg/ml). For non-Enterobacteriaceae strains, MIC₅₀ values ranged from 2 to 8 μg/ml, with the exception of Campylobacter spp., for which all strains had MIC values of >512 μg/ml. Rifamycin SV also demonstrated excellent activity (MIC₅₀ of ≤ 0.03 μg/ml) against most C. difficile strains (including one hypervirulent NAP1 strain), and this activity was even superior to the potency observed for vancomycin, metronidazole, and rifaximin. In mutational passaging studies, rifamycin SV induced stable resistance and showed a mutation frequency in E. coli similar to that of rifampin. This study presents the potency of rifamycin SV for enteropathogens commonly recovered from patients with TD and CDAD. Additional in vitro and in vivo studies appear necessary to determine the utility of rifamycin SV as an oral agent for the prevention and treatment of TD and CDAD.
authors.affiliation: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA. david-farrell@jmilabs.com
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.forename: Shannon D
authors.initials: SD
authors.lastname: Putnam
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Biedenbach
authors.forename: Luigi
authors.initials: L
authors.lastname: Moro
authors.forename: Roberta
authors.initials: R
authors.lastname: Bozzella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Celasco
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016360:Clostridioides difficile / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D003967:Diarrhea / Q000382:microbiology*; D054307:Enterotoxigenic Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012294:Rifamycins / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D012294:Rifamycins; C023808:rifamycin SV