title: Severe lactic acidosis associated with linezolid use in a patient with the mitochondrial DNA A2706G polymorphism.
abstract: Linezolid, an oxazolidinone antimicrobial, exerts its effect by binding to bacterial 23S ribosomal RNA, preventing the formation of the initiation complex. Its use is associated with reversible hyperlactatemia and lactic acidosis, and inhibition of mitochondrial protein synthesis may be the mechanism underlying this adverse effect. We describe a 35-year-old woman who developed severe lactic acidosis after she received linezolid for 35 days to treat a disseminated infection with Mycobacterium avium-intracellulare complex. This patient was found to have the mitochondrial DNA polymorphism A2706G, a variation previously suggested to predispose individuals to linezolid-associated lactic acidosis. In the future, increased understanding of the mitochondrial genome and its associated polymorphisms may allow us to identify patients at risk for adverse effects that were previously classified as idiosyncratic.
authors.affiliation: Department of Pharmacy, St. Peter's Hospital, Albany, New York 12208, USA. jcarson@stpetershealthcare.org
authors.forename: John
authors.initials: J
authors.lastname: Carson
authors.forename: Jorge
authors.initials: J
authors.lastname: Cerda
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Chae
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Peter
authors.initials: P
authors.lastname: Maggiore
mesh_terms: D000081:Acetamides / Q000009:adverse effects*; D000140:Acidosis, Lactic / Q000139:chemically induced*; D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects*; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D000069349:Linezolid; D015269:Mycobacterium avium Complex / Q000187:drug effects; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy; D023303:Oxazolidinones / Q000009:adverse effects*; D011110:Polymorphism, Genetic
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D004272:DNA, Mitochondrial; D023303:Oxazolidinones; D000069349:Linezolid