title: Counting pyrazinamide in regimens for multidrug-resistant tuberculosis.
abstract: BACKGROUND
  For treatment of multidrug-resistant tuberculosis, World Health Organization (WHO) guidelines recommend four likely effective drugs plus pyrazinamide (PZA), irrespective of the likely effectiveness of PZA in an individual patient. Whether this regimen should be supplemented in the absence of likely PZA effectiveness is an open question.
  
  
  OBJECTIVE
  The objectives of this study were to examine (1) whether individuals receiving four likely effective drugs (based on documented susceptibility or no prior exposure) experienced higher mortality during the intensive phase of treatment than those receiving five likely effective drugs and (2) whether the WHO-recommended regimen (four likely effective drugs plus PZA) may be compromised in individuals in whom PZA is not likely effective.
  
  
  METHODS
  Among 668 patients, we compared the hazard of death across regimen groups characterized by the number of likely effective drugs and whether pyrazinamide was one of the likely effective drugs.
  
  
  RESULTS
  Relative to five likely effective drugs, regimens of four likely effective drugs and the WHO-recommended regimen used in individuals in whom PZA was not likely effective were associated with higher mortality rates (respectively, adjusted hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.35-6.09 and adjusted HR, 2.76; 95% CI, 0.92-8.27). The mortality rate for a regimen of five likely effective drugs with likely effective PZA was similar to that for the regimen of five likely effective drugs without PZA (HR, 1.00; 95% CI, 0.12-8.00).
  
  
  CONCLUSIONS
  Mortality may be reduced by the inclusion of five likely effective drugs, including an injectable, during the intensive phase of treatment. If PZA is unlikely to be effective in an individual patient, these results suggest adding a different, likely effective drug.
authors: 1 Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts.
authors: Molly F
authors: MF
authors: Franke
authors: Mercedes C
authors: MC
authors: Becerra
authors: Dylan B
authors: DB
authors: Tierney
authors: Michael L
authors: ML
authors: Rich
authors: Cesar
authors: C
authors: Bonilla
authors: Jaime
authors: J
authors: Bayona
authors: Megan M
authors: MM
authors: McLaughlin
authors: Carole D
authors: CD
authors: Mitnick
mesh_terms: D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D011718:Pyrazinamide / Q000008:administration & dosage*; D012189:Retrospective Studies; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide
keywords: drug resistance; mortality; tuberculosis drug therapy