Kibdelomycin is a potent and selective agent against toxigenic Clostridium difficile Journal Article

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Authors: Miesel, L.; Hecht, D. W.; Osmolski, J. R.; Gerding, D.; Flattery, A.; Li, F.; Lan, J.; Lipari, P.; Polishook, J. D.; Liang, L.; Liu, J; Olsen, D. B.; Singh, S. B.
Article Title: Kibdelomycin is a potent and selective agent against toxigenic Clostridium difficile
Abstract: Clostridium difficile is the causative agent of C. difficile-associated diarrhea (CDAD), with increased risk in elderly populations. Kibdelomycin, a novel natural-product inhibitor of type II topoisomerase enzymes, was evaluated for activity against C. difficile and gastrointestinal anaerobic organisms. Toxigenic C. difficile isolates (n=168) from U.S. hospitals and anaerobic Gram-positive and Gram-negative organisms (n=598) from Chicago-area hospitals were tested. Kibdelomycin showed potent activity against toxigenic C. difficile (MIC90=0.25 mug/ml) and most Gram-positive aerobic organisms but had little activity against Bacteroides species (MIC5032 mug/ml; n=270). Potent anti-C. difficile activity was also observed in the hamster model of C. difficile colitis. Dosing at 1.6 mg/kg (twice-daily oral dose) resulted in protection from a lethal infection and a 2-log reduction in C. difficile cecal counts. A 6.25-mg/kg twice-daily oral dose completely eliminated detectable C. difficile counts in cecal contents. A single 6.25-mg/kg oral dose showed that cecal contents were exposed to the drug at 2 muM (eightfold higher than the MIC), with no significant plasma exposure. These findings support further exploration of kibdelomycin for development of an anti-C. difficile agent.
Journal Title: Antimicrobial Agents and Chemotherapy
Volume: 58
Issue: 4
ISSN: 1098-6596; 0066-4804
Publisher: Unknown  
Journal Place: United States
Date Published: 2014
Start Page: 2387
End Page: 2392
Language: eng
DOI/URL:

10.1128/AAC.00021-14
Notes: JID: 0315061; OID: NLM: PMC4023737 [Available on 10/01/14]; PMCR: 2014/10/01 00:00; 2014/02/10 [aheadofprint]; ppublish