Drug-associated adverse events and their relationship with outcomes in patients receiving treatment for extensively drug-resistant tuberculosis in South Africa

PLoS One. 2013 May 7;8(5):e63057. doi: 10.1371/journal.pone.0063057. Print 2013.

Abstract

Background: Treatment-related outcomes in patients with extensively drug-resistant tuberculosis (XDR-TB) are poor. However, data about the type, frequency and severity of presumed drug-associated adverse events (AEs) and their association with treatment-related outcomes in patients with XDR-TB are scarce.

Methods: Case records of 115 South-African XDR-TB patients were retrospectively reviewed by a trained researcher. AEs were estimated and graded according to severity [grade 0 = none; grade 1-2 = mild to moderate; and grade 3-5 = severe (drug stopped, life-threatening or death)].

Findings: 161 AEs were experienced by 67/115(58%) patients: 23/67(34%) required modification of treatment, the offending drug was discontinued in 19/67(28%), reactions were life-threatening in 2/67(3.0%), and 6/67(9.0%) died. ∼50% of the patients were still on treatment at the time of data capture. Sputum culture-conversion was less likely in those with severe (grade 3-5) vs. grade 0-2 AEs [2/27(7%) vs. 24/88(27%); p = 0.02]. The type, frequency and severity of AEs was similar in HIV-infected and uninfected patients. Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in five patients and hypokalemia in one patient).

Conclusion: Drug-associated AEs occur commonly with XDR-TB treatment, are often severe, frequently interrupt therapy, and negatively impact on culture conversion outcomes. These preliminary data inform on the need for standardised strategies (including pre-treatment counselling, early detection, monitoring, and follow-up) and less toxic drugs to optimally manage patients with XDR-TB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / adverse effects*
  • Antitubercular Agents / therapeutic use*
  • Demography
  • Dose-Response Relationship, Drug
  • Extensively Drug-Resistant Tuberculosis / complications
  • Extensively Drug-Resistant Tuberculosis / drug therapy*
  • Extensively Drug-Resistant Tuberculosis / microbiology
  • Extensively Drug-Resistant Tuberculosis / mortality
  • Female
  • HIV Infections / complications
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Multivariate Analysis
  • Mycobacterium tuberculosis
  • South Africa / epidemiology
  • Treatment Outcome

Substances

  • Antitubercular Agents

Grant support

KD is supported by a South Africa MRC Fellowship, the EU (FW7 TB Susgent) and the EDCTP European and Developing Countries Clinical Trails Partnership. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.