Three quarters of South African patients with extensively drug-resistant (XDR) tuberculosis died within 5 years of treatment, according to results of a 107-patient analysis in three South African provinces. Among people with HIV infection, taking antiretroviral therapy (ART) was independently associated with survival.
XDR TB is Mycobacterium tuberculosis resistant to isoniazid, rifampin, any fluoroquinolone, and at least one of three injectable second-line drugs, such as amikacin, kanamycin, or capreomycin. Infection with XDR TB poses a grave threat to HIV-positive people in countries with high rates of both infections.
To get a better understanding of long-term treatment outcomes in people with XDR TB, researchers prospectively monitored 107 patients in South African from March 2008 to August 2012. All had been diagnosed with XDR TB between August 2002 and February 2008, and 44 people (41%) had HIV infection. The investigators genotyped virus from 56 patients to establish strain type and permit extended susceptibility testing.
All patients received empiric inpatient treatment including a median of 8 anti-TB drugs (interquartile range [IQR] 6 to 10). Of the 56 genotyped isolates, 36 (64%) were resistant to at least 8 drugs. Resistance to an increasing number of agents was associated with the Beijing genotype (P = 0.01).
After 24 months of follow-up, 49 of 107 patients (46%) had died, treatment had failed in 25 (23%), 7 (7%) had interrupted treatment for at least 2 months, and 17 people (16%) had a favorable treatment outcome (cure or treatment completion). After 60 months of follow-up, 78 people (73%) had died, treatment had failed in 11 (10%), 4 patients (4%) had interrupted treatment for at least 2 months, and 12 (11%) had a favorable treatment outcome.
Median survival after treatment failure was 19.84 months (IQR 4.16 to 26.04). Among 45 people discharged from the hospital, 26 (58%) achieved sputum culture conversion and 19 (42%) failed treatment. Overall, only 22 of 107 patients (21%) achieved sputum culture conversion in a median 8.7 months (IQR 5.6 to 26.4).
Independent predictors of sputum culture conversion were not having a history of multidrug-resistant TB (P = 0.0007) and treatment with clofazamine (P = 0.0069). Treatment with clofazamine (P = 0.021) and culture conversion (P < 0.0001) independently predicted survival. In people with HIV infection, antiretroviral therapy independently predicted survival (P = 0.003).
“In South Africa, long-term outcomes in patients with XDR tuberculosis are poor, irrespective of HIV status,” the researchers conclude. They note that many XDR TB patients with positive sputum cultures are discharged from the hospital because long-term or palliative-care facilities are scarce. As a result, they “are likely to transmit disease into the wider community.”
The authors see an urgent need for studies of new anti-TB combinations. And they call on policy makers to implement interventions that minimize TB spread by XDR TB patients in whom treatment failed.
Source: Elize Pietersen, 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. Lancet 2014; Jan 16. pii: S0140-6736(13)62675-6.
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For more on XDR TB from the CDC