title: Time to detection of the growth of Mycobacterium tuberculosis in MGIT 960 for determining the early bactericidal activity of antituberculosis agents.
abstract: Evaluation of early bactericidal activity (EBA) by the determination of a fall in viable colony-forming units (CFU) of Mycobacterium tuberculosis in sputum is a first step in the clinical study of new antituberculosis agents. The time to detection (TTD) of growth in liquid media is more sensitive and could substitute for CFU counting on solid media. Overnight sputum samples collected during the evaluation of the novel agent TMC207 in comparison to isoniazid and rifampicin were studied. For the determination of CFU, we incubated 10-fold dilutions of homogenized sputum on selective 7H10 agar. The TTD was measured by incubating decontaminated sputum in the BACTEC MGIT 960 system. The fall in bacillary load over 7 days determined by CFU counting closely matched the prolongation of the TTD in the BACTEC MGIT 960 system. The CFU counts correlated significantly with the TTD. While the ranking of agents and different dosages of TMC207 was similar, the highest dose of TMC207 showed markedly better activity when measured by the TTD than CFU counting when compared to the activity of isoniazid. Automated TTD could augment, or, in future, replace, CFU counting to determine sputum bacillary load in EBA clinical trials pending a more formal evaluation of the correlation of the measurements.
authors.affiliation: Department of Molecular Biology and Human Genetics, and MRC Centre for Molecular and Cellular Biology, DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa. ahd@sun.ac.za
authors.forename: A H
authors.initials: AH
authors.lastname: Diacon
authors.forename: J S
authors.initials: JS
authors.lastname: Maritz
authors.forename: A
authors.initials: A
authors.lastname: Venter
authors.forename: P D
authors.initials: PD
authors.lastname: van Helden
authors.forename: K
authors.initials: K
authors.lastname: Andries
authors.forename: D F
authors.initials: DF
authors.lastname: McNeeley
authors.forename: P R
authors.initials: PR
authors.lastname: Donald
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015169:Colony Count, Microbial; D003470:Culture Media; D064687:Diarylquinolines; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development*; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology; D013183:Sputum / Q000382:microbiology; D013997:Time Factors; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D003470:Culture Media; D064687:Diarylquinolines; D011804:Quinolines; C493870:bedaquiline; D007538:Isoniazid; D012293:Rifampin
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