SI
SI
discoversearch

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor.  We ask that you disable ad blocking while on Silicon Investor in the best interests of our community.  If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.
Biotech / Medical : Microcide Pharmaceuticals (MCDE)
 Public ReplyPrvt ReplyMark as Last ReadFilePrevious 10Next 10PreviousNext  
To: scaram(o)uche who wrote (163)8/29/1999 1:49:00 PM
From: scaram(o)uche   of 186
 
sorry, I can't get the table to cut and paste......

Session: Inhibitors of Bacterial and Fungal Efflux Pumps
Location:
Exhibit Hall
Session Date:
Monday, 9/27/99
Session Time:
3:00 pm - 4:30 pm

Potentiation of Levofloxacin (Levo) by a Broad-Spectrum Efflux Pump Inhibitor
(EPI) in Mouse Models of Infection Caused by Pseudomonas aeruginosa

D. Griffith, O. Lomovskaya, V. Lee, M. Dudley
Microcide Pharmaceuticals, Inc.: Mountain View, CA

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 30mg/kg q4h alone or with varying doses and
dosing intervals of the EPI. The CFU/thigh were determined at varying time points up to
24h 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 (ED50) at
72h 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.
Report TOU ViolationShare This Post
 Public ReplyPrvt ReplyMark as Last ReadFilePrevious 10Next 10PreviousNext  

HomeMailHotSubjectMarksPeopleMarksKeepersSettings
Terms Of UseContact UsCopyright/IP PolicyPrivacy PolicyAbout UsFAQAdvertise on SI
© 2025 Knight Sac Media.  Data provided by Twelve Data, Alpha Vantage, and CityFALCON News