Time to detection of the growth of Mycobacterium tuberculosis in MGIT 960 for determining the early bactericidal activity of antituberculosis agents
Date
2010, 2010
Authors
Diacon A.H.
Maritz J.S.
Venter A.
Van Helden P.D.
Andries K.
McNeeley D.F.
Donald P.R.
Diacon A.H.
Maritz J.S.
Venter A.
Journal Title
Journal ISSN
Volume Title
Publisher
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. © 2010 Springer-Verlag.
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. © 2010 Springer-Verlag.
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. © 2010 Springer-Verlag.
Description
Keywords
isoniazid; rifampicin; adult; article; bacterial count; bacterial growth; bactericidal activity; bacterium detection; bacterium examination; clinical article; colony forming unit; controlled study; female; human; liquid culture; male; Mycobacterium tuberculosis; nonhuman; priority journal; sputum culture; time to detection; tuberculosis; Adolescent; Adult; Antitubercular Agents; Colony Count, Microbial; Culture Media; Female; Humans; Isoniazid; Male; Middle Aged; Mycobacterium tuberculosis; Quinolines; Rifampin; Sputum; Time Factors; Treatment Outcome; Tuberculosis, Pulmonary; Young Adult, isoniazid, rifampicin, adult, article, bacterial count, bacterial growth, bactericidal activity, bacterium detection, bacterium examination, clinical article, colony forming unit, controlled study, female, human, liquid culture, male, Mycobacterium tuberculosis, nonhuman, priority journal, sputum culture, time to detection, tuberculosis, Adolescent, Adult, Antitubercular Agents, Colony Count, Microbial, Culture Media, Female, Humans, Isoniazid, Male, Middle Aged, Mycobacterium tuberculosis, Quinolines, Rifampin, Sputum, Time Factors, Treatment Outcome, Tuberculosis, Pulmonary, Young Adult
Citation
European Journal of Clinical Microbiology and Infectious Diseases
29
12
European Journal of Clinical Microbiology and Infectious Diseases
29
12
29
12
European Journal of Clinical Microbiology and Infectious Diseases
29
12