Drug-drug interactions and safety of linezolid, tedizolid, and other oxazolidinones.

Oxazolidinones are synthetic antimicrobials with strong bacteriostatic activity against Gram-positive organisms. Recently, tedizolid phosphate was approved for clinical use becoming the second agent of this class after linezolid available in clinical practice. Oxazolidinone pharmacology including structure-activity relationships, mode of action, pharmacokinetics, drug-drug interactions, and adverse drug reactions is reviewed. Furthermore, bacterial resistance, approved indications, use in paediatric populations, and tuberculosis treatment with oxazolidinones are discussed, and differences in indications and pharmacotoxicological properties between the two approved agents are elucidated. A MEDLINE PubMed search for articles published in English from January 1960 to June 2015 was completed using the terms: oxazolidinone, oxazolidinone-induced toxicity, oxazolidinone pharmacokinetics, serotonin syndrome, oxazolidinone drug-drug interactions, antituberculotic treatment. Linezolid illustrates an important antimicrobial in several Gram-positive infections especially when methicillin-resistant Staphylococcus aureus strains are involved. Myelosuppression and neuropathy are toxicities of high relevance particularly in case of prolonged treatment periods. The significance of linezolid in the treatment of extensively drug-resistant tuberculosis has to be further investigated. Tedizolid phosphate represents a welcome addition in our anti-infective arsenal, and future research will clarify its role in indications other than the already approved acute bacterial skin infections.

Citation

Antonios Douros, Katja Grabowski, Ralf Stahlmann. Drug-drug interactions and safety of linezolid, tedizolid, and other oxazolidinones. Expert opinion on drug metabolism & toxicology. 2015;11(12):1849-59

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PMID: 26457865

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