title: Efficacy and safety of World Health Organization group 5 drugs for multidrug-resistant tuberculosis treatment.
abstract: The efficacy and toxicity of several drugs now used to treat multidrug-resistant tuberculosis (MDR-TB) have not been fully evaluated. We searched three databases for studies assessing efficacy in MDR-TB or safety during prolonged treatment of any mycobacterial infections, of drugs classified by the World Health Organization as having uncertain efficacy for MDR-TB (group 5). We included 83 out of 4002 studies identified. Evidence was inadequate for meropenem, imipenem and terizidone. For MDR-TB treatment, clarithromycin had no efficacy in two studies (risk difference (RD) -0.13, 95% CI -0.40-0.14) and amoxicillin-clavulanate had no efficacy in two other studies (RD 0.07, 95% CI -0.21-0.35). The largest number of studies described prolonged use for treatment of non-tuberculous mycobacteria. Azithromycin was not associated with excess serious adverse events (SAEs). Clarithromycin was not associated with excess SAEs in eight controlled trials in HIV-infected patients (RD 0.00, 95% CI -0.02-0.02), nor in six uncontrolled studies in HIV-uninfected patients, whereas six uncontrolled studies in HIV-infected patients clarithromycin caused substantial SAEs (proportion 0.20, 95% CI 0.12-0.27). For most group 5 drugs we found inadequate evidence of safety for prolonged use or for efficacy for MDR-TB, although macrolides appeared to be safe in prolonged use.
authors.affiliation: Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, QC, Canada Dept of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Winters
authors.affiliation: Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, QC, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Butler-Laporte
authors.affiliation: Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, QC, Canada Dept of Epidemiology and Biostatistics, McGill University, Montreal, QC, Canada Dick.Menzies@mcgill.ca.
authors.forename: Dick
authors.initials: D
authors.lastname: Menzies
mesh_terms: D000658:Amoxicillin / Q000009:adverse effects / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017963:Azithromycin / Q000009:adverse effects / Q000627:therapeutic use; D015377:Cilastatin / Q000009:adverse effects / Q000627:therapeutic use; D017291:Clarithromycin / Q000009:adverse effects / Q000627:therapeutic use; D019818:Clavulanic Acid / Q000009:adverse effects / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications; D006801:Humans; D015378:Imipenem / Q000009:adverse effects / Q000627:therapeutic use; D007555:Isoxazoles / Q000009:adverse effects / Q000627:therapeutic use; D018942:Macrolides / Q000009:adverse effects / Q000627:therapeutic use; D000077731:Meropenem; D009169:Mycobacterium tuberculosis; D023303:Oxazolidinones / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013845:Thienamycins / Q000009:adverse effects / Q000627:therapeutic use; D013881:Thioridazine / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*; D014944:World Health Organization
chemical_list: D000995:Antitubercular Agents; D007555:Isoxazoles; D018942:Macrolides; D023303:Oxazolidinones; D013845:Thienamycins; C100142:terizidone; D015377:Cilastatin; D019818:Clavulanic Acid; D015378:Imipenem; D000658:Amoxicillin; D017963:Azithromycin; D000077731:Meropenem; D017291:Clarithromycin; D013881:Thioridazine