title: Comparison of time to positive and colony counting in an early bactericidal activity study of anti-tuberculosis treatment.
abstract: METHODS
  Patients with smear-positive, newly diagnosed pulmonary tuberculosis (TB) presenting to the out-patient TB clinic in Kampala, Uganda.
  
  
  OBJECTIVE
  To compare colony-forming unit (cfu) counting and time to positive (TTP) in Mycobacteria Growth Indicator Tube (MGIT) culture as measures of early bactericidal activity (EBA).
  
  
  METHODS
  Patients were enrolled in an EBA feasibility study of standard TB chemotherapy. Sixteen-hour overnight sputum collections were obtained before and on days 2, 4, 7, 10, 12 and 14 of treatment for quantitative culture on selective Middlebrook 7H11 agar media and TTP in the MGIT liquid culture system.
  
  
  RESULTS
  Log cfu and TTP were correlated over all time points (r(s) = -0.71, P < 0.001). Within-subject (day to day) variation as a percentage of total variation was very similar between the two measures: 25.7% for cfu and 25% for TTP. Mean EBA 0-14, 0-2 and 2-14 measured by TTP were similar to those previously reported.
  
  
  CONCLUSIONS
  TTP measured by an automated, standardized, commercially available culture system correlates with cfu determinations. EBA measured by TTP provides similar information to cfu counting, and is reproducible across sites and in different patient populations. These findings support replacing cfu counting with TTP as the primary measurement in EBA studies.
authors.affiliation: Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Bark
authors.forename: P
authors.initials: P
authors.lastname: Gitta
authors.forename: S
authors.initials: S
authors.lastname: Ogwang
authors.forename: M
authors.initials: M
authors.lastname: Nsereko
authors.forename: B A
authors.initials: BA
authors.lastname: Thiel
authors.forename: W H
authors.initials: WH
authors.lastname: Boom
authors.forename: K D
authors.initials: KD
authors.lastname: Eisenach
authors.forename: M L
authors.initials: ML
authors.lastname: Joloba
authors.forename: J L
authors.initials: JL
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D057205:Automation, Laboratory; D015169:Colony Count, Microbial; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000627:therapeutic use; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D014454:Uganda; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin