title: Direct Susceptibility Testing of Mycobacterium tuberculosis for Pyrazinamide by Use of the Bactec MGIT 960 System.
abstract: Pyrazinamide (PZA) is a key antituberculosis drug, yet no rapid susceptibility test is commercially available. PZA drug susceptibility testing (DST) was performed directly on sputum samples from 327 patients and compared with the indirect method by using the Bactec MGIT 960 system in the context of patient screening for participation in a drug trial. Compared to standard indirect PZA DST, direct DST was successful in only 59% of cases, but results obtained were highly accurate and available faster. Agreement between the direct and indirect methods varied from 90 to 100% in each laboratory. The median times for obtaining PZA results from the time when the specimen was collected ranged from 11 to 16 days for the direct test and 18 to 95 days for the indirect test across laboratories. The direct method is accurate and reproducible across laboratories. It can be expected to accelerate results in >50% of cases, but it cannot replace indirect DST for PZA. Phenotypic methods remain the gold standard for DST in drug trials. If future studies can optimize the method to decrease the number of uninterpretable results, direct MGIT DST could be the new phenotypic DST standard for clinical trials, providing more rapid detection of resistance to new drugs in experimental regimens.
authors.affiliation: Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Demers
authors.affiliation: MRC Centre for Molecular and Cellular Biology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Amour
authors.initials: A
authors.lastname: Venter
authors.affiliation: Division of Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Sven O
authors.initials: SO
authors.lastname: Friedrich
authors.affiliation: National Institute of Medical Research, Mbeya Medical Research Center, Mbeya, Tanzania.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rojas-Ponce
authors.affiliation: National Institute of Medical Research, Mbeya Medical Research Center, Mbeya, Tanzania.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mapamba
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland Ifakara Health Institute, Bagamoyo, Tanzania.
authors.forename: Levan
authors.initials: L
authors.lastname: Jugheli
authors.affiliation: Ifakara Health Institute, Bagamoyo, Tanzania.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sasamalo
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa.
authors.forename: Deepak
authors.initials: D
authors.lastname: Almeida
authors.affiliation: KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa.
authors.forename: Afton
authors.initials: A
authors.lastname: Dorasamy
authors.affiliation: Clinical Laboratory Services, Division of Wits Health Consortium and School of Pathology, Johannesburg, South Africa.
authors.forename: Ute
authors.initials: U
authors.lastname: Jentsch
authors.affiliation: Clinical Laboratory Services, Division of Wits Health Consortium and School of Pathology, Johannesburg, South Africa.
authors.forename: Mara
authors.initials: M
authors.lastname: Gibson
authors.affiliation: Global Alliance for TB Drug Development, New York, New York, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Everitt
authors.affiliation: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA eisenachkathleend@uams.edu.
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Eisenach
authors.affiliation: Division of Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Diacon
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011718:Pyrazinamide / Q000494:pharmacology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D013997:Time Factors
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide