title: 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.
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.
authors.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
authors.forename: Venkata G
authors.initials: VG
authors.lastname: Meka
authors.forename: Satish K
authors.initials: SK
authors.lastname: Pillai
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
authors.forename: Christine
authors.initials: C
authors.lastname: Wennersten
authors.forename: Lata
authors.initials: L
authors.lastname: Venkataraman
authors.forename: Paola C
authors.initials: PC
authors.lastname: DeGirolami
authors.forename: George M
authors.initials: GM
authors.lastname: Eliopoulos
authors.forename: Robert C
authors.initials: RC
authors.lastname: Moellering
authors.forename: Howard S
authors.initials: HS
authors.lastname: Gold
mesh_terms: D000081:Acetamides / Q000494:pharmacology* / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use; D001769:Blood / Q000382:microbiology; D015139:Blotting, Southern; D002876:Chromosomes, Bacterial / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry / Q000302:isolation & purification; D004275:DNA, Ribosomal / Q000737:chemistry / Q000302:isolation & purification; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D017353:Gene Deletion; D018628:Gene Dosage; D020459:Genes, rRNA; D006801:Humans; D000069349:Linezolid; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D009154:Mutation; D023303:Oxazolidinones / Q000494:pharmacology* / Q000627:therapeutic use; D017354:Point Mutation; D012329:RNA, Bacterial / Q000235:genetics; D012338:RNA, Ribosomal, 23S / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D023303:Oxazolidinones; D012329:RNA, Bacterial; D012338:RNA, Ribosomal, 23S; D000069349:Linezolid