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

• Published in: PloS one 2013-05, Vol.8 (5), p.e63057
• Main Authors: Shean, Karen, Streicher, Elizabeth, Pieterson, Elize, Symons, Greg, van Zyl Smit, Richard, Theron, Grant, Lehloenya, Rannakoe, Padanilam, Xavier, Wilcox, Paul, Victor, Tommie C, van Helden, Paul, Grobusch, Martin P, Groubusch, Martin, Warren, Robin, Badri, Motasim, Dheda, Keertan
• Format: Article
• Language: English
• Subjects: Antitubercular agents; Antitubercular Agents - adverse effects; Antitubercular Agents - therapeutic use; Capreomycin; Cellular biology; Clinical outcomes; Conversion; Data capture; Demography; Dose-Response Relationship, Drug; Drug resistance; Drug therapy; Drugs; Epidemiology; Extensively Drug-Resistant Tuberculosis - complications; Extensively Drug-Resistant Tuberculosis - drug therapy; Extensively Drug-Resistant Tuberculosis - microbiology; Extensively Drug-Resistant Tuberculosis - mortality; Female; Health sciences; HIV Infections - complications; Humans; Hypokalemia; Infections; Infectious diseases; Kaplan-Meier Estimate; Kidneys; Laboratories; Male; Medical research; Medicine; Microbial drug resistance; Multidrug resistant organisms; Multivariate Analysis; Mycobacterium tuberculosis; Patient outcomes; Patients; Renal failure; South Africa - epidemiology; Sputum; Treatment Outcome; Tropical diseases; Tuberculosis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063057

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. 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)]. 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). 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.