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 |
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Authors: | Meka Venkata G Pillai Satish K Sakoulas George Wennersten Christine Venkataraman Lata DeGirolami Paola C Eliopoulos George M Moellering Robert C Gold Howard S |
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Affiliation: | Division of Infectious Diseases, Department of Medicine, and Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. vmeka@bidmc.harvard.edu |
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Abstract: | 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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