VENEZIA RA, EVANS AM, PRESTON KE, GRAFFUNDER EM; 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. C1-64.

University of Maryland School of Medicine, Baltimore, MD.

BACKGROUND: Levofloxacin was previously shown to be a risk factor [OR 8.01] for MRSA. Exposure of heteroresistant strains of MRSA to ciprofloxacin and levofloxacin enhanced the selection of oxacillin resistance, while gatifloxacin enhanced the least. GRN, a novel des-F(6)- quinolone with more gram positive activity, was studied for its effect on selection of oxacillin resistance. METHODS: Quinolone susceptible, mecA positive, heteroresistant strains of S. aureus were exposed to GRN, gatifloxacin, levofloxacin or ciprofloxacin. The strains were grown in tryptic soy (TS) broth at 37degreesC for 8 and 24 hours with either varying concentrations or no drug. In separate experiments, omeprazole was added up to 250 microg/ml to the quinolones to inhibit the cellular efflux pump. Serial dilutions were plated on TS agar with 2% NaCl and oxacillin ranging from 0 to 128 microg/ml. The proportion of oxacillin resistant colonies was determined. RESULTS: GRN did not increase the proportion of colonies that grew on agar containing 128 microg/ml oxacillin while the others did. The oxacillin resistant population replicated more slowly than the parent strain. It appears that quinolones increased the proportion of oxacillin resistant bacteria by selectively killing the rapidly dividing oxacillin susceptible population. Addition of omeprazole enhanced the bactericidal activity of the quinolones for the more oxacillin resistant population. CONCLUSIONS: We hypothesize that the intracellular quinolone concentration is reduced via efflux pump in the slowly dividing oxacillin resistant population before cell death can occur. This gives a selective advantage to cells that are highly resistant to oxacillin. GRN exhibited greater killing of the oxacillin resistant population due to its greater activity. Clinical use of GRN may reduce quinolone associated selection of MRSA.

Publication Types:

• Meeting Abstracts

Keywords:

• 5'-N-methylcarboxamideadenosine
• Adenosine
• Agar
• Ciprofloxacin
• Fluoroquinolones
• Ofloxacin
• Oxacillin
• Selection (Genetics)
• Staphylococcal Infections
• Staphylococcus aureus
• gatifloxacin
• genetics

Other ID:

• GWAIDS0025485

UI: 102265109

From Meeting Abstracts