@article{10.1371/journal.pone.0063057, doi = {10.1371/journal.pone.0063057}, author = {Shean, Karen AND Streicher, Elizabeth AND Pieterson, Elize AND Symons, Greg AND van Zyl Smit, Richard AND Theron, Grant AND Lehloenya, Rannakoe AND Padanilam, Xavier AND Wilcox, Paul AND Victor, Tommie C. AND van Helden, Paul AND Groubusch, Martin AND Warren, Robin AND Badri, Motasim AND Dheda, Keertan}, journal = {PLOS ONE}, publisher = {Public Library of Science}, title = {Drug-Associated Adverse Events and Their Relationship with Outcomes in Patients Receiving Treatment for Extensively Drug-Resistant Tuberculosis in South Africa}, year = {2013}, month = {05}, volume = {8}, url = {https://doi.org/10.1371/journal.pone.0063057}, pages = {1-10}, 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 Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in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.}, number = {5}, }