Griffith D, Lomovskaya O, Lee V, Dudley M; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 327 (abstract no. 1268).
Microcide Pharmaceuticals, Inc., Mountain View, CA, USA
We have previously shown that overexpression of the MexAB-OprM efflux pump in PA results in reduced efficacy with Levo and ciprofloxacin. A prototypical lead for a series of broad-spectrum EPIs for Mex-type pumps in PA with MexAB-OprM over-expressed (Levo MIC alone/+10 mg/L of EPI = 2/0.125 mg/L) was tested in the neutropenic mouse thigh and mouse sepsis models. In the neutropenic mouse thigh model, mice were treated with Levo 30 mg/kg q4h alone or with varying doses and dosing intervals of the EPI. The CFU/thigh were determined at varying time points up to 24 h after inoculation. In the sepsis model, mice were treated with varying doses of Levo alone, or in combination with 25 or 50 mg/kg of the EPI. Results in the neutropenic mouse thigh model (see Table) showed dose-related potentiation with more rapid effects with more frequent EPI dosing. In the sepsis model, co-administration of the EPI reduced the Levo dose required for 50% survival (ED[50]) at 72 h from 100 mg/kg to 69 and 28 mg/kg for the 25 and 50 mg/kg EPI dose groups, respectively. These data show that Levo activity against PA in vivo can be potentiated by inhibition of efflux pumps associated with drug resistance. [table: see text].
Publication Types:
Keywords:
- Animals
- Ciprofloxacin
- Mice
- Microbial Sensitivity Tests
- Ofloxacin
- Pseudomonas aeruginosa
- antagonists & inhibitors
- etiology
- instrumentation
Other ID:
UI: 102246681
From Meeting Abstracts