title: Utility of Second-Generation Line Probe Assay (Hain MTBDRplus) Directly on 2-Month Sputum Specimens for Monitoring Tuberculosis Treatment Response.
abstract: The utility of a line probe assay (Genotype MTBDRplus) performed directly on 2-month sputa to monitor tuberculosis treatment response is unknown. We assessed if direct testing of 2-month sputa with MTBDRpluscan predict 2-month culture conversion and long-term treatment outcome. Xpert MTB/RIF-confirmed rifampin-susceptible tuberculosis cases were recruited at tuberculosis diagnosis and followed up at 2 and 5 to 6 months. MTBDRpluswas performed directly on 2-month sputa and on all positive cultured isolates at 2 and 5 to 6 months. We also investigated the association of a positive direct MTBDRplusat 2 months with subsequent unsuccessful tuberculosis treatment outcome (failure/death during treatment or subsequent disease recurrence). A total of 279 patients (62% of whom were HIV-1 coinfected) were recruited. Direct MTBDRplusat 2 months had a sensitivity of 78% (95% confidence interval [CI], 65 to 87) and specificity of 80% (95% CI, 74 to 84) to predict culture positivity at 2 months with a high negative predictive value of 93% (95% CI, 89 to 96). Inconclusive genotypic susceptibility results for both rifampin and isoniazid were seen in 26% of MTBDRplustests performed directly on sputum. Compared to a reference of MTBDRplusperformed on positive cultures, the false-positive resistance rate for direct testing of MTBDRpluson sputa was 4% for rifampin and 2% for isoniazid. While a positive 2-month smear was not significantly associated with an unsuccessful treatment outcome (adjusted odds ratio [aOR], 2.69; 95% CI, 0.88 to 8.21), a positive direct MTBDRplusat 2 months was associated with an unsuccessful outcome (aOR 2.87; 95% CI, 1.11 to 7.42). There is moderate utility of direct 2-month MTBDRplusto predict culture conversion at 2 months and also to predict an unfavorable outcome.
authors.affiliation: Department of Medicine, Imperial College, London, United Kingdom neesha.rockwood@doctors.org.uk.|Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors.forename: Neesha
authors.identifier: 0000-0002-7830-1394
authors.initials: N
authors.lastname: Rockwood
authors.affiliation: National Health Laboratory Service, Groote Schuur Hospital, Cape Town, Republic of South Africa.|Division of Microbiology, Department of Pathology, University of Cape Town, Cape Town, Republic of South Africa.
authors.forename: Justyna
authors.initials: J
authors.lastname: Wojno
authors.affiliation: National Health Laboratory Service, Groote Schuur Hospital, Cape Town, Republic of South Africa.|Division of Microbiology, Department of Pathology, University of Cape Town, Cape Town, Republic of South Africa.
authors.forename: Yonas
authors.initials: Y
authors.lastname: Ghebrekristos
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.|National Health Laboratory Service, Groote Schuur Hospital, Cape Town, Republic of South Africa.|Division of Microbiology, Department of Pathology, University of Cape Town, Cape Town, Republic of South Africa.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Nicol
authors.affiliation: Department of Medicine, Imperial College, London, United Kingdom.|Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.|Department of Medicine, University of Cape Town, Cape Town, Republic of South Africa.
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.affiliation: Department of Medicine, Imperial College, London, United Kingdom.|Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa.|Department of Medicine, University of Cape Town, Cape Town, Republic of South Africa.|The Francis Crick Institute, London, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D025202:Molecular Diagnostic Techniques / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011446:Prospective Studies; D012293:Rifampin / Q000627:therapeutic use*; D013183:Sputum / Q000382:microbiology*; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin
keywords: bacterial biomarker; drug resistance; line probe assay; treatment outcome; tuberculosis