Long-term outcomes of patients with extensively drug-resistant tuberculosis in South Africa: a cohort study

• Published in: The Lancet (British edition) 2014-04, Vol.383 (9924), p.1230-1239
• Main Authors: Pietersen, Elize, MSSc, Ignatius, Elisa, MD, Streicher, Elizabeth M, PhD, Mastrapa, Barbara, MD, Padanilam, Xavier, MCFP, Pooran, Anil, MSc, Badri, Motasim, PhD, Lesosky, Maia, PhD, van Helden, Paul, Prof, Sirgel, Frederick A, PhD, Warren, Robin, PhD, Dheda, Keertan, Prof
• Format: Article
• Language: English
• Subjects: Adult; Antiretroviral agents; Antitubercular Agents - therapeutic use; Bacterial diseases; Biological and medical sciences; Clinical outcomes; Coinfection - complications; Coinfection - mortality; Developing countries; Disease spread; Drug therapy; Extensively Drug-Resistant Tuberculosis - complications; Extensively Drug-Resistant Tuberculosis - drug therapy; Extensively Drug-Resistant Tuberculosis - mortality; Female; General aspects; HIV; HIV Infections - complications; HIV Infections - mortality; Human bacterial diseases; Human immunodeficiency virus; Humans; Infectious diseases; Internal Medicine; Kaplan-Meier Estimate; LDCs; Male; Medical research; Medical sciences; Middle Aged; Miscellaneous; Mortality; Mycobacterium; Prospective Studies; Public health. Hygiene; Public health. Hygiene-occupational medicine; South Africa - epidemiology; Sputum - microbiology; Treatment Outcome; Tuberculosis; Tuberculosis and atypical mycobacterial infections
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(13)62675-6

Summary Background Long-term treatment-related outcomes in patients with extensively drug-resistant (XDR) tuberculosis are unknown. We followed up a cohort of patients to address knowledge gaps. Methods Between March, 2008, and August, 2012, we prospectively followed up a cohort of 107 patients from three provinces in South Africa, who had been diagnosed with XDR tuberculosis between August 2002, and February, 2008. Available isolates from 56 patients were genotyped to establish strain type and used for extended susceptibility testing. Findings All patients were treated empirically as inpatients with a median of eight drugs (IQR six to ten). 44 patients (41%) had HIV. 36 (64%) of 56 isolates were resistant to at least eight drugs, and resistance to an increasing number of drugs was associated with the Beijing genotype (p=0·01). After 24 months of follow-up, 17 patients (16%) had a favourable outcome (ie, treatment cure or completion), 49 (46%) had died, seven (7%) had defaulted (interruption of treatment for at least 2 consecutive months), and 25 (23%) had failed treatment. At 60 months, 12 patients (11%) had a favourable outcome, 78 (73%) had died, four (4%) had defaulted, and 11 (10%) had failed treatment. 45 patients were discharged from hospital, of whom 26 (58%) had achieved sputum culture conversion and 19 (42%) had failed treatment. Median survival of patients who had failed treatment from time of discharge was 19·84 months (IQR 4·16–26·04). Clustering of cases and transmission within families containing a patient who had failed treatment and been discharged were shown with genotypic methods. Net sputum culture conversion occurred in 22 patients (21%) and median time to net culture conversion was 8·7 months (IQR 5·6–26·4). Independent predictors of probability of net culture conversion were no history of multidrug-resistant tuberculosis (p=0·0007) and use of clofazamine (p=0·0069). Independent overall predictors of survival were net culture conversion (p