title: Linezolid for the treatment of drug-resistant tuberculosis in children: a review and recommendations.
abstract: Options for the treatment of children with drug-resistant tuberculosis (DR-TB) are limited. Emerging evidence in adults from systematic reviews and a randomized trial has shown good efficacy of linezolid in difficult cases of DR-TB but with frequent serious adverse effects. Published data in children are limited and we are unaware of formal guidelines for linezolid in treatment of paediatric DR-TB, though it will likely be an important component of DR-TB treatment for a growing number of children. We performed a structured review of existing literature on the efficacy, adverse effects, pharmacokinetics and pharmacodynamics of linezolid in DR-TB, highlighting the key evidence from the adult literature and systematically evaluating published paediatric data. Our search identified 8 reports of 18 children receiving linezolid for difficult to treat DR-TB. All 18 had culture conversion and 15 of 18 had successful long-term treatment outcomes. Adverse events were reported in 9 of 18; a linezolid dose reduction was required in 5 of 18, and 2 of 18 permanently discontinued linezolid because of adverse events. We make specific recommendations for the use of linezolid in children with DR-TB, and identify priority questions for future research. For children with multidrug-resistant (MDR)-TB with additional resistance or with extensively drug-resistant (XDR)-TB, linezolid may make the difference between a successful or poor outcome, and until newer antituberculosis agents with better efficacy and safety become available in children, linezolid will be an important component of treatment for children with the worst forms of DR-TB.
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address: garciaprats@sun.ac.za.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Garcia-Prats
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address: pcrose@sun.ac.za.
authors.forename: Penelope C
authors.initials: PC
authors.lastname: Rose
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address: annekeh@sun.ac.za.
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Hesseling
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address: hss@sun.ac.za.
authors.forename: H Simon
authors.initials: HS
authors.lastname: Schaaf
mesh_terms: D000081:Acetamides / Q000494:pharmacology / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D006801:Humans; D000069349:Linezolid; D023303:Oxazolidinones / Q000494:pharmacology / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000081:Acetamides; D000995:Antitubercular Agents; D023303:Oxazolidinones; D000069349:Linezolid
keywords: Linezolid; MDR-TB; Tuberculosis; XDR-TB; children