DE SOUZA NJ, DESHPANDE PK, BHAWSAR SB, BHAVSAR SV, SHINDE PS, CHATURVEDI NC, YEOLE RD, SHUKLA MC, PATEL MV, GUPTE SV, JAFRI M, UPADHYAY DJ, BHAGWAT S, KHORAKIWALA HF; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. C1-63.

Wockhardt Res. Centre, Aurangabad, India.

BACKGROUND: Multidrug efflux is a major cause of intrinsic and acquired drug resistance in many microorganisms to evade the effects of some antimicrobial agents. PA, EC, SPN and SA possess efflux pumps that transport selected FQs, tetracyclines, macrolides, aminoglycosides and cationic agents . One strategy to target resistant mechanisms of such microbial self-defense is to search for inhibitors of microbial efflux pumps. METHODS: A library of about 1000 in-house FQs was screened including S-(-)-nadifloxacin (Nadi), its arginine salt (WCK 771) and WCK 1152, prepared by condensing 4-amino- or 4-hydroxy-piperidines with known FQ cores and subsequent optional derivatisation. Screening methods for identification of EP inhibitors/potentiators of PA 27813, EC 2051 and SPN 3514 was done by antibiotic diffusion assay in combination with levofloxacin (Levo) for PA and EC and azithromycin (Azi) for SPN. The zone diameter difference between the drug in absence and in presence of EP inhibitor/potentiator was the criteria used. Inhibitors of NorA in SA 1199B were identified by determining the FIC index using ciprofloxacin. RESULTS: Levo against PA and EC was potentiated by WCK 1152, WCK 919 (racemic WCK 1152), aminoacyl derivatives of (RS)- and (S)-Nadi (zone diameter differences of 9 -18 mm) (b) Azi against SPN was potentiated by WCK 1152, WCK 919 and derivatives thereof (zone diameter differences of 11 - 13 mm) and (c) 6 nadifloxacin related FQs inhibited SA EP (FIC index 0.19 - 0.40), the best NorA inhibitor being the N-methylpiperidinyl-4-hydroxy ester of S-Nadi (FIC Index 0.18). CONCLUSIONS: WCK 1152, WCK 771 and derivatives thereof are capable of inhibiting multidrug EPs in PA, EC, SPN, and SA. They also can improve the clinical utility of selected FQs and macrolides.

Publication Types:

• Meeting Abstracts

Keywords:

• Anti-Bacterial Agents
• Anti-Infective Agents
• Ciprofloxacin
• Fluoroquinolones
• Ofloxacin
• Quinolizines
• WCK 771
• nadifloxacin
• p-Aminosalicylic Acid

Other ID:

• GWAIDS0025484

UI: 102265108

From Meeting Abstracts