GRIFFITH DC, CORCORAN E, SORENSEN K, CHO D, LOMOVSKAYA O, DUDLEY MN; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. F-340.
Microcide Pharmaceuticals, Mountain View, CA
We have previously shown that the addition of a novel class of efflux pump inhibitors (EPI) can enhance the in vitro activity of levofloxacin (LVX) against P. aeruginosa, and azithromycin (AZM) against gram-negative bacteria expressing the AcrAB efflux pump. In this report, we describe the efficacy of LVX and AZM in combination with MC-04,124, a new EPI. In the neutropenic mouse thigh and mouse sepsis models of infection, LVX and MC-04,124 were evaluated against a strain of P. aeruginosa (PAM 1032) that over-expresses the MexAB-OprM efflux pump. In a mouse pyelopnephritis model, AZM and MC-04,124 were evaluated against a strain of E. coli that over-expresses the AcrAB efflux pump. RESULTS: In the mouse sepsis model, the addition of MC-04,124 reduced the LVX ED[50] (dose associated with 50% survival at 72h) from 100 mg/kg (95% CI: 76-142) to 46 mg/kg (95% CI: 30-62). Results in the thigh and pyelonephritis models: [table: see text] These data show that the efflux pump inhibitor MC-04,124 enhances the activity of these agents in vivo.
Publication Types:
Keywords:
- Animals
- Azithromycin
- Escherichia coli
- Escherichia coli Proteins
- In Vitro
- Mice
- Ofloxacin
- Pseudomonas aeruginosa
Other ID:
UI: 102269884
From Meeting Abstracts