Pietersen, Elize, Elisa Ignatius, Elizabeth M. Streicher, Barbara Mastrapa, Xavier Padanilam, Anil Pooran, Motasim Badri, Maia Lesosky, Paul van Helden, Frederick A Sirgel, Robin Warren, Keertan Dheda. “Long-Term Outcomes of Patients with Extensively Drug-Resistant Tuberculosis in South Africa: A Cohort Study,” The Lancet 383, no. 9924 (2014): 1230-1239.

URL: www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962675-6/fulltext

Abstract

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.

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<0·0001) and treatment with clofazamine (p=0·021). Antiretroviral therapy was also a predictor of survival in patients with HIV (p=0·003).

Interpretation: In South Africa, long-term outcomes in patients with XDR tuberculosis are poor, irrespective of HIV status. Because appropriate long-stay or palliative care facilities are scarce, substantial numbers of patients with XDR tuberculosis who have failed treatment and have positive sputum cultures are being discharged from hospital and are likely to transmit disease into the wider community. Testing of new combined regimens is needed urgently and policy makers should implement interventions to minimise disease spread by patients who fail treatment.

Along with the rise in HIV, tuberculosis (TB) infection is also on the rise. Drug resistant forms of TB are circulating in South Africa, including an extensively drug-resistant form (XDR-TB). Pietersen et al. followed a cohort of XDR-TB patients in South Africa and found that patients who did not respond to treatment were discharged from the hospital and were likely infect others. The researchers confirmed the emergence of a strain of XDR-TB that failed to respond to any known drugs and cite an urgent need for increased palliative care facilities and new mixed treatment regimens to prevent the epidemic from spiraling out of control. The researchers’ findings provide important new information that may change treatment protocols to prevent the additional development of drug resistance in cases where a positive outcome is unlikely.