This Article Full Text Full Text (PDF) Other Versions of this Article: AAC.00430-07v1 51/9/3235    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by DeMarco, C. E. Articles by Kaatz, G. W. Search for Related Content PubMed PubMed Citation Articles by DeMarco, C. E. Articles by Kaatz, G. W.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 2007, p. 3235-3239, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.00430-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Efflux-Related Resistance to Norfloxacin, Dyes, and Biocides in Bloodstream Isolates of Staphylococcus aureus

The John D. Dingell Department of Veterans Affairs Medical Center,¹ Department of Medicine, Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, Michigan 48201²

Received 28 March 2007/ Returned for modification 4 May 2007/ Accepted 12 June 2007

Efflux is an important resistance mechanism in Staphylococcus aureus, but its frequency in patients with bacteremia is unknown. Nonreplicate bloodstream isolates were collected over an 8-month period, and MICs of four common efflux pump substrates, with and without the broad-spectrum efflux pump inhibitor reserpine, were determined (n = 232). A reserpine-associated fourfold decrease in MIC was considered indicative of efflux. Strains exhibiting efflux of at least two of the four substrates were identified ("effluxing strains" [n = 114]). For these strains, MICs with or without reserpine for an array of typical substrates and the expression of mepA, mdeA, norA, norB, norC, and qacA/B were determined using quantitative real-time reverse transcription-PCR (qRT-PCR). A fourfold or greater increase in gene expression was considered significant. The most commonly effluxed substrates were ethidium bromide and chlorhexidine (100 and 96% of effluxing strains, respectively). qRT-PCR identified strains overexpressing mepA (5 [4.4%]), mdeA (13 [11.4%]), norA (26 [22.8%]), norB (29 [25.4%]), and norC (19 [16.7%]); 23 strains overexpressed two or more genes. Mutations probably associated with increased gene expression included a MepR-inactivating substitution and norA promoter region insertions or deletions. Mutations possibly associated with increased expression of the other analyzed genes were also observed. Effluxing strains comprised 49% of all strains studied (114/232 strains), with nearly half of these overexpressing genes encoding MepA, MdeA, and/or NorABC (54/114 strains). Reduced susceptibility to biocides may contribute to persistence on environmental surfaces, and efflux of drugs such as fluoroquinolones may predispose strains to high-level target-based resistance.

Published ahead of print on 18 June 2007.