title: Baseline predictors of sputum culture conversion in pulmonary tuberculosis: importance of cavities, smoking, time to detection and W-Beijing genotype.
abstract: BACKGROUND
  Time 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.
  
  
  OBJECTIVE
  To assess baseline predictors of failure of sputum culture conversion, within the first 2 months of antitubercular therapy, in participants with pulmonary tuberculosis.
  
  
  METHODS
  Between 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.
  
  
  RESULTS
  113 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.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: School of Public Health, University of the Western Cape, Cape Town, South Africa. marianne.visser@gmail.com
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Visser
authors.forename: Michael C
authors.initials: MC
authors.lastname: Stead
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.forename: Rob
authors.initials: R
authors.lastname: Warren
authors.forename: Michael
authors.initials: M
authors.lastname: Schomaker
authors.forename: Harleen M S
authors.initials: HM
authors.lastname: Grewal
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Swart
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003786:Dental Pulp Cavity / Q000382:microbiology* / Q000502:physiology; D019587:Dietary Supplements; D018450:Disease Progression; D004352:Drug Resistance, Microbial; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008828:Microbiological Techniques; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects / Q000235:genetics; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D013183:Sputum / Q000382:microbiology*; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000178:diet therapy / Q000235:genetics / Q000382:microbiology; D014801:Vitamin A / Q000008:administration & dosage; D055815:Young Adult; D015032:Zinc / Q000008:administration & dosage
chemical_list: D014801:Vitamin A; D015032:Zinc