Drug-Associated Adverse Events and Their Relationship with Outcomes in Patients Receiving Treatment for Extensively Drug-Resistant Tuberculosis in South Africa

• DOI: 10.1371/journal.pone.0063057
• Publication Date: 2013-05-08T01:23:19Z
• Authors: Karen Shean; Elizabeth Streicher; Elize Pieterson; Greg Symons; Richard van Zyl Smit; Grant Theron; Rannakoe Lehloenya; Xavier Padanilam; Paul Wilcox; Tommie C. Victor; Paul van Helden; Martin Groubusch; Robin Warren; Motasim Badri; Keertan Dheda
• Keywords: Extensively drug-resistant tuberculosis; Culture conversion; Capreomycin; Sputum culture; Multi-drug-resistant tuberculosis; Pharmacotherapy

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) their association treatment-related XDR-TB scarce. Methods Case records 115 South-African were retrospectively reviewed by a trained researcher. AEs estimated graded according to [grade 0 = none; grade 1–2 mild moderate; 3–5 severe (drug stopped, life-threatening or death)]. Findings 161 experienced 67/115(58%) patients: 23/67(34%) required modification treatment, offending drug was discontinued 19/67(28%), reactions 2/67(3.0%), 6/67(9.0%) died. ∼50% still on treatment at time capture. Sputum culture-conversion less likely those (grade 3–5) vs. 0–2 [2/27(7%) 24/88(27%); p 0.02]. The similar HIV-infected uninfected patients. Capreomycin, which empirically administered most cases, withdrawn 14/104(14%) patients, implicated (14/34) 41% total withdrawals, associated all 6 deaths AE group (renal failure five hypokalemia one patient). Conclusion Drug-associated occur commonly often severe, frequently interrupt therapy, negatively impact culture conversion outcomes. These preliminary inform need for standardised strategies (including pre-treatment counselling, early detection, monitoring, follow-up) toxic drugs optimally manage XDR-TB.