title: Drug-associated adverse events and their relationship with outcomes in patients receiving treatment for extensively drug-resistant tuberculosis in South Africa.
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)].
  
  
  RESULTS
  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 Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Karen
authors.initials: K
authors.lastname: Shean
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Streicher
authors.forename: Elize
authors.initials: E
authors.lastname: Pieterson
authors.forename: Greg
authors.initials: G
authors.lastname: Symons
authors.forename: Richard
authors.initials: R
authors.lastname: van Zyl Smit
authors.forename: Grant
authors.initials: G
authors.lastname: Theron
authors.forename: Rannakoe
authors.initials: R
authors.lastname: Lehloenya
authors.forename: Xavier
authors.initials: X
authors.lastname: Padanilam
authors.forename: Paul
authors.initials: P
authors.lastname: Wilcox
authors.forename: Tommie C
authors.initials: TC
authors.lastname: Victor
authors.forename: Paul
authors.initials: P
authors.lastname: van Helden
authors.forename: Martin P
authors.initials: MP
authors.lastname: Grobusch
authors.forename: Martin
authors.initials: M
authors.lastname: Groubusch
authors.forename: Robin
authors.initials: R
authors.lastname: Warren
authors.forename: Motasim
authors.initials: M
authors.lastname: Badri
authors.forename: Keertan
authors.initials: K
authors.lastname: Dheda
mesh_terms: D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D003710:Demography; D004305:Dose-Response Relationship, Drug; D054908:Extensively Drug-Resistant Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000995:Antitubercular Agents