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JAC Advance Access published online on September 3, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh423
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received June 23, 2004
Revised August 9, 2004
Accepted August 10, 2004

Brief report

Reversion to susceptibility in a linezolid-resistant clinical isolate of Staphylococcus aureus

Venkata G. Meka 1*, Howard S. Gold 1, Amy Cooke 2, Lata Venkataraman 3, George M. Eliopoulos 1, Robert C. Moellering Jr4, and Stephen G. Jenkins 5

1 Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA USA
2 Department of Pharmacy, Carolinas Medical Center, Charlotte, NC, USA
3 Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA USA
4 Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
5 Division of Microbiology and Immunology, Department of Pathology, Carolinas Medical Center, Charlotte, NC, USA

* To whom correspondence should be addressed. E-mail: vmeka{at}bidmc.harvard.edu.


  Abstract

Objectives: Linezolid resistance in rare isolates of Staphylococcus aureus has been associated with G2576T mutations in domain V of the 23S rRNA gene. We report the analysis of a clinical S. aureus isolate that developed linezolid resistance (MIC of linezolid of 12 mg/L) after a 25 day course of the drug. Sequencing identified G2576T mutations in four of the five copies of the 23S rRNA gene.

Methods: To examine the stability of this resistance, we serially passaged this original isolate 60 times over a 75 day period on antimicrobial-free medium.

Results: After 30 passages, the MIC of linezolid had decreased to 8 mg/L and only two of the five copies of the 23S rRNA gene contained the G2576T mutation. After 60 passages, the MIC of linezolid fell to 2 mg/L and only one of the five 23S rRNA gene copies contained the mutation. The original and two passaged staphylococci were indistinguishable by pulsed-field gel electrophoresis.

Conclusions: In the absence of antibiotic pressure, linezolid resistance was unstable in a clinical isolate that did not have all copies of the 23S rRNA gene mutated, although a single copy of mutant rDNA was maintained. Gene conversion was probably the mechanism for this reversion, using the wild-type 23S rRNA gene sequences to replace the G2576T mutation by homologous recombination.

Keywords: G2576T mutation; 23S rRNA gene; gene conversion.
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