Linezolid Resistance in Sequential Staphylococcus aureus Isolates Associated with a T2500A Mutation in the 23S rRNA Gene and Loss of a Single Copy of rRNA.
Meka, Venkata G. 1,3; Pillai, Satish K. 1,3; Sakoulas, George 4; Wennersten, Christine 1; Venkataraman, Lata 2; DeGirolami, Paola C. 2,3; Eliopoulos, George M. 1,3; Moellering, Robert C. 1,3; Gold, Howard S. 1,3
[Article] Journal of Infectious Diseases. 190(2):311-317, July 15, 2004.

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: Linezolid is an important therapeutic option for infections caused by resistant gram-positive bacteria. We report the characterization of sequential methicillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates that developed resistance in a patient treated with a prolonged course of linezolid. Analysis of this series of clinical MRSA isolates detected, in the resistant isolates, the presence of a T2500A mutation in the domain V region of the 23S rRNA gene. In addition, the loss of a single copy of the 23S rRNA gene was found in 2 of the resistant isolates. As a result of these 2 factors, the proportion of mutant: wild-type 23S rRNA genes increased in association with an increase in the minimum inhibitory concentration of linezolid. The most recent isolate of this series was recovered 7 months after the patient discontinued linezolid and demonstrated reversion to a susceptible phenotype associated with a loss of the T2500A mutation.

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