Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method

Eur Respir J. 2016 Oct;48(4):1160-1170. doi: 10.1183/13993003.00462-2016. Epub 2016 Sep 1.

Abstract

Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.

Publication types

  • Meta-Analysis
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antitubercular Agents / therapeutic use*
  • Cohort Studies
  • Coinfection
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mycobacterium tuberculosis / drug effects
  • Proportional Hazards Models
  • Risk
  • Sputum / microbiology
  • Treatment Failure
  • Tuberculosis, Multidrug-Resistant / therapy*
  • Tuberculosis, Pulmonary / diagnosis

Substances

  • Antitubercular Agents