title: Efficacy and safety of a four-drug fixed-dose combination regimen versus separate drugs for treatment of pulmonary tuberculosis: a systematic review and meta-analysis.
abstract: BACKGROUND
  Tuberculosis, particularly multi-drug-resistant tuberculosis, is a major cause of morbidity and mortality worldwide. To the best of our knowledge, however, no study to date has assessed the combined use of the four available drugs for tuberculosis treatment, which is an issue of great clinical relevance.
  
  
  OBJECTIVE
  To determine whether the four-drug fixed-dose combination is safer or more effective than separate drugs for treatment of pulmonary tuberculosis.
  
  
  METHODS
  A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
  
  
  RESULTS
  In pooled results from five randomized controlled trials with 3502 patients across Africa, Asia, and Latin America, four-drug fixed-dose combination therapy was no better than separate drugs therapy in terms of culture conversion after 2 and 6 months of treatment. There were no significant differences between the groups in overall incidence of adverse effects. However, the meta-analytic measure (log odds ratio) revealed that separate drugs treatment had a 1.65 [exp (0.5)=1.65] increased chance of gastrointestinal adverse effects compared to four-drug fixed-dose combination treatment.
  
  
  CONCLUSIONS
  The reviewed studies showed that four-drug fixed-dose combination therapy provides greater patient comfort by reducing the number of pills and the incidence of gastrointestinal adverse effects, as well as simplifying pharmaceutical management at all levels.
authors.affiliation: Laboratório Central de Saúde Pública (LACEN) - Brasília, Departamento de Biologia Médica, Seção Micobaterial, Brasília, DF, Brazil. Electronic address: glauracaldo@gmail.com.
authors.forename: Glaura C
authors.initials: GC
authors.lastname: Lima
authors.affiliation: Universidade de Brasília, Faculdade de Ceilândia, Brasília, DF, Brazil.
authors.forename: Emilia V
authors.initials: EV
authors.lastname: Silva
authors.affiliation: Universidade de Brasília, Departamento de Farmácia, Brasília, DF, Brazil.
authors.forename: Pérola de O
authors.initials: PO
authors.lastname: Magalhães
authors.affiliation: Universidade de Brasília, Departamento de Farmácia, Brasília, DF, Brazil.
authors.forename: Janeth S
authors.initials: JS
authors.lastname: Naves
mesh_terms: D000349:Africa; D000569:Americas; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D007843:Latin America; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D004338:Drug Combinations