title: The diagnostic accuracy of the MTBDRplus and MTBDRsl assays for drug-resistant TB detection when performed on sputum and culture isolates.
abstract: Although molecular tests for drug-resistant TB perform well on culture isolates, their accuracy using clinical samples, particularly from TB and HIV-endemic settings, requires clarification. The MTBDRplus and MTBDRsl line probe assays were evaluated in 181 sputum samples and 270 isolates from patients with culture-confirmed drug-sensitive-TB, MDR-TB, or XDR-TB. Phenotypic culture-based testing was the reference standard. Using sputum, the sensitivities for resistance was 97.7%, 95.4%, 58.9%, 61.6% for rifampicin, isoniazid, ofloxacin, and amikacin, respectively, whereas the specificities were 91.8%, 89%, 100%, and 100%, respectively. MTBDRsl sensitivity differed in smear-positive vs. smear-negative samples (79.2% vs. 20%, p < 0.0001 for ofloxacin; 72.9% vs. 37%, p = 0.0023 for amikacin) but not by HIV status. If used sequentially, MTBDRplus and MTBDRsl could rule-in XDR-TB in 78.5% (22/28) and 10.5% (2/19) of smear-positive and smear-negative samples, respectively. On culture isolates, the sensitivity for resistance to rifampicin, isoniazid, ofloxacin, and amikacin was 95.1%, 96.1%, 72.3% and 76.6%, respectively, whereas the specificities exceeded 96%. Using a sequential testing approach, rapid sputum-based diagnosis of fluoroquinolone or aminoglycoside-resistant TB is feasible only in smear-positive samples, where rule-in value is good. Further investigation is required in samples that test susceptible in order to rule-out second-line drug resistance.
authors: Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors: Michele
authors: M
authors: Tomasicchio
authors: Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.|Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors: Grant
authors: G
authors: Theron
authors: Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors: Elize
authors: E
authors: Pietersen
authors: Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors: Elizabeth
authors: E
authors: Streicher
authors: Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors: Danielle
authors: D
authors: Stanley-Josephs
authors: Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors: Paul
authors: P
authors: van Helden
authors: Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors: Rob
authors: R
authors: Warren
authors: Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.|Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors: Keertan
authors: K
authors: Dheda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000627:therapeutic use; D001681:Biological Assay / Q000379:methods*; D024901:Drug Resistance, Multiple, Bacterial; D054908:Extensively Drug-Resistant Tuberculosis / Q000175:diagnosis* / Q000382:microbiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D011379:Prognosis; D012293:Rifampin / Q000627:therapeutic use; D013183:Sputum / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin