What is the best culture conversion prognostic marker for patients treated for multidrug-resistant tuberculosis?

INTRODUCTION: Identification of good prognostic marker for tuberculosis (TB) treatment response is a necessary step on the path towards a surrogate marker to reduce TB trial duration.METHODS: We performed a retrospective analysis on routinely collected data in 6 drug-resistant TB (DRTB) programs. Culture conversion, defined as two consecutive negative cultures, was assessed, and performance of culture conversion at Month 2 and Month 6 to predict treatment success were explored. To explore factors associated with positive predicted value (PPV) and the specificity of culture conversion, a multinomial logistic regression was fitted.RESULTS: This study included 634 patients: 68.5% were males; the median age was 35 years, 75.2% were previously treated for TB, 59.4% were resistant only to isoniazid and rifampicin and 18.1% resistant to fluoroquinolones. Culture conversion at Month 2 and 6 showed similar PPV while specificity was much higher for culture conversion at Month 2: 91.3% (95%CI 86.1-95.1). PPV of culture conversion at Month 2 did not vary strongly according to patients' characteristics, while specificity was slightly higher among patients with fluoroquinolone-resistant strains.CONCLUSION: Culture conversion at Month 2 is an acceptable prognostic marker for MDR-TB treatment. Considering the advantage of using an earlier marker, further evaluation as a surrogate marker is warranted to shorten TB trials.

Identification of patients who could benefit from bedaquiline or delamanid: a multisite MDR-TB cohort study.

BACKGROUND: The World Health Organization recommends adding bedaquiline or delamanid to multidrug-resistant tuberculosis (MDR-TB) regimens for which four effective drugs are not available, and delamanid for patients at high risk of poor outcome. OBJECTIVE: To identify patients at risk of unfavourable outcomes who may benefit from the new drugs. METHODS: Retrospective cohort study of treatment outcomes involving four to five effective drugs for 15-24 months in programmes in Uzbekistan, Georgia, Armenia, Swaziland and Kenya between 2001 and 2011. RESULTS: Of 1433 patients, 48.5% had body mass index (BMI) <18.5 kg/m(2), 72.9% had a high bacillary load, 16.7% were resistant to two injectables, 2.9% were resistant to ofloxacin (OFX) and 3.0% had extensively drug-resistant TB (XDR-TB). Treatment success ranged from 59.7% (no second-line resistance) to 27.0% (XDR-TB). XDR-TB (aOR 8.16, 95%CI 3.22-20.64), resistance to two injectables (aOR 1.90, 95%CI 1.00-3.62) or OFX (aOR 5.56, 95%CI 2.15-14.37), past incarceration (aOR 1.88, 95%CI 1.11-3.2), history of second-line treatment (aOR 3.24, 95%CI 1.53-6.85), low BMI (aOR 2.22, 95%CI 1.56-3.12) and high bacillary load (aOR 2.32, 95%CI 1.15-4.67) were associated with unfavourable outcomes. Patients started on capreomycin rather than kanamycin were more likely to have an unfavourable outcome (aOR 1.54, 95%CI 1.04-2.28). CONCLUSION: In our cohort, patients who may benefit from bedaquiline and delamanid represented up to two thirds of all MDR-TB patients.

Gender differences in treatment outcomes among 15-49 year olds with smear-positive pulmonary tuberculosis in Kenya.

OBJECTIVE: To determine gender differences in treatment outcomes among 15-49 year olds with smear-positive pulmonary tuberculosis (PTB) and factors associated with poor outcomes in Kenya. DESIGN: Retrospective descriptive cohort. RESULTS: Of 16 056 subjects analysed, 38% were female and 62% male. Females had a higher risk of poor treatment outcome than males (12% vs. 10%, P < 0.001; adjusted OR 1.29, 95%CI 1.16-1.44, P < 0.001). In the first multivariate model, restricting the analysis to human immunodeficiency virus (HIV) positive patients and adjusting for risk factors and clustering, females had a non-significantly lower risk of poor outcome (OR 0.99, 95%CI 0.86-1.13, P = 0.844). In the model restricted to HIV-negative patients, a non-significantly lower risk was found (OR 0.89, 95%CI 0.73-1.09, P = 0.267). In the second model, restricting analysis to patients on antiretroviral therapy (ART) and adjusting for risk factors and clustering, females had a non-significantly lower risk of poor PTB treatment outcomes (OR 0.98, 95%CI 0.84-1.14, P = 0.792). In the model restricted to HIV-positive patients not on ART, a non-significantly higher risk was found (OR 1.15, 95%CI 0.79-1.67, P = 0.461). CONCLUSION: Females of reproductive age are likely to have poorer treatment outcomes than males. Among females, not commencing ART during anti-tuberculosis treatment seemed to be associated with poor outcomes.