Format

Send to

Choose Destination
Antimicrob Agents Chemother. 2014 Oct;58(10):5714-8. doi: 10.1128/AAC.02903-14. Epub 2014 Jul 14.

In vivo assessment of SMT19969 in a hamster model of clostridium difficile infection.

Author information

1
University of North Texas Health Science Center, Fort Worth, Texas, USA william.weiss@unthsc.edu.
2
University of North Texas Health Science Center, Fort Worth, Texas, USA.
3
Summit plc, Oxfordshire, United Kingdom.

Abstract

SMT19969 [2,2'-bis(4-pyridyl)3H,3'-H 5,5-bibenzimidazole] is a novel narrow-spectrum nonabsorbable antibiotic currently in development for the treatment of Clostridium difficile infection. The comparative activities of SMT19969 and vancomycin against nonepidemic and epidemic strains of C. difficile were studied in an established hamster model. Against nonepidemic (VA11) strains, the survival rates of SMT19969-treated animals ranged from 80% to 95%. Vancomycin exhibited 100% protection during treatment, with relapse observed starting on day 9 and 50% survival at day 20. At 50 mg/kg of body weight, SMT19969 administered orally once daily for 5 days provided full protection of treated animals on the dosing days and through day 12 against epidemic strains. Vancomycin also protected during the dosing interval, but apparent relapse occurred earlier, starting on day 11. SMT19969 exhibited excellent in vitro activity, with MICs of 0.25 μg/ml for all isolates. The MICs for vancomycin were 2- to 4-fold higher at ≤0.5 to 1 μg/ml. All plasma sample concentrations of SMT19969 were below the limit of quantification (25 ng/ml) at all time points, consistent with the reported lack of bioavailability of the compound. Cecal concentrations were significantly above the MIC (ranging from 96 μg/ml to 172 μg/ml).

PMID:
25022586
PMCID:
PMC4187990
DOI:
10.1128/AAC.02903-14
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center