Abstract
BackgroundTime to detection (TTD) on automated liquid mycobacterial cultures is an emerging biomarker of tuberculosis outcomes. The M. tuberculosis W-Beijing genotype is spreading globally, indicating a selective advantage. There is a paucity of data on the association between baseline TTD and W-Beijing genotype and tuberculosis outcomes.AimTo assess baseline predictors of failure of sputum culture conversion, within the first 2 months of antitubercular therapy, in participants with pulmonary tuberculosis.DesignBetween May 2005 and August 2008 we conducted a prospective cohort study of time to sputum culture conversion in ambulatory participants with first episodes of smear and culture positive pulmonary tuberculosis attending two primary care clinics in Cape Town, South Africa. Rifampicin resistance (diagnosed on phenotypic susceptibility testing) was an exclusion criterion. Sputum was collected weekly for 8 weeks for mycobacterial culture on liquid media (BACTEC MGIT 960). Due to missing data, multiple imputation was performed. Time to sputum culture conversion was analysed using a Cox-proportional hazards model. Bayesian model averaging determined the posterior effect probability for each variable.Results113 participants were enrolled (30.1% female, 10.5% HIV-infected, 44.2% W-Beijing genotype, and 89% cavities). On Kaplan Meier analysis 50.4% of participants underwent sputum culture conversion by 8 weeks. The following baseline factors were associated with slower sputum culture conversion: TTD (adjusted hazard ratio (aHR) = 1.11, 95% CI 1.02; 1.2), lung cavities (aHR = 0.13, 95% CI 0.02; 0.95), ever smoking (aHR = 0.32, 95% CI 0.1; 1.02) and the W-Beijing genotype (aHR = 0.51, 95% CI 0.25; 1.07). On Bayesian model averaging, posterior probability effects were strong for TTD, lung cavitation and smoking and moderate for W-Beijing genotype.ConclusionWe found that baseline TTD, smoking, cavities and W-Beijing genotype were associated with delayed 2 month sputum culture. Larger studies are needed to confirm the relationship between the W-Beijing genotype and sputum culture conversion.
Highlights
Tuberculosis cure after anti-tubercular therapy is best measured by bacteriological relapse within 2 years after completion of treatment
The following baseline factors were associated with slower sputum culture conversion: Time to detection (TTD) (adjusted hazard ratio = 1.11, 95% CI 1.02; 1.2), lung cavities, ever smoking and the W-Beijing genotype
On Bayesian model averaging, posterior probability effects were strong for TTD, lung cavitation and smoking and moderate for W-Beijing genotype
Summary
Tuberculosis cure after anti-tubercular therapy is best measured by bacteriological relapse within 2 years after completion of treatment. Sputum culture conversion after 2 months of treatment is a recognized surrogate biomarker of cure [1,2]. Time to detection (TTD) on automated liquid mycobacterial cultures reflects mycobacterial load more accurately than sputum smear or culture grading, and has been shown to predict month 2 culture conversion, tuberculosis recurrence and relapse [3,4]. Time to detection (TTD) on automated liquid mycobacterial cultures is an emerging biomarker of tuberculosis outcomes. There is a paucity of data on the association between baseline TTD and W-Beijing genotype and tuberculosis outcomes
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