title: Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method.
abstract: Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.
authors: Dept of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA Partners in Health, Boston, MA, USA carole_mitnick@hms.harvard.edu.
authors: Carole D
authors: CD
authors: Mitnick
authors: Dept of Infectious Disease Epidemiology, Norwegian Institute of Public Health, Oslo, Norway Dept of Health Statistics, Norwegian Institute of Public Health, Oslo, Norway.
authors: Richard A
authors: RA
authors: White
authors: Dept of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA Brigham and Women's Hospital, Division of Global Health Equity, Boston, MA, USA.
authors: Chunling
authors: C
authors: Lu
authors: Dept of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
authors: Carly A
authors: CA
authors: Rodriguez
authors: Socios en Salud Sucursal, Lima, Peru.
authors: Jaime
authors: J
authors: Bayona
authors: Dept of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA Partners in Health, Boston, MA, USA Brigham and Women's Hospital, Division of Global Health Equity, Boston, MA, USA.
authors: Mercedes C
authors: MC
authors: Becerra
authors: Dept of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USA.
authors: Marcos
authors: M
authors: Burgos
authors: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate, Italy.
authors: Rosella
authors: R
authors: Centis
authors: Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.
authors: Theodore
authors: T
authors: Cohen
authors: Médecins Sans Frontières, Cape Town, South Africa.
authors: Helen
authors: H
authors: Cox
authors: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate, Italy Public Health Consulting Group, Lugano, Switzerland.
authors: Lia
authors: L
authors: D'Ambrosio
authors: Tartu University Hospital, Lung Clinic, Tartu, Estonia.
authors: Manfred
authors: M
authors: Danilovitz
authors: Global TB Programme, World Health Organization, Geneva, Switzerland.
authors: Dennis
authors: D
authors: Falzon
authors: Partners in Health Russia, Moscow, Russia.
authors: Irina Y
authors: IY
authors: Gelmanova
authors: Makati Medical Center, Manila, Philippines.
authors: Maria T
authors: MT
authors: Gler
authors: Tuberculosis Control, San Francisco Department of Public Health, San Francisco, CA, USA.
authors: Jennifer A
authors: JA
authors: Grinsdale
authors: US Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: Timothy H
authors: TH
authors: Holtz
authors: Dept of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA Partners in Health, Boston, MA, USA Brigham and Women's Hospital, Division of Global Health Equity, Boston, MA, USA.
authors: Salmaan
authors: S
authors: Keshavjee
authors: State Agency for Tuberculosis and Lung Diseases (TPSVA), Riga, Latvia.
authors: Vaira
authors: V
authors: Leimane
authors: Montreal Chest Institute, McGill University, Montreal, QC, Canada.
authors: Dick
authors: D
authors: Menzies
authors: WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate, Italy.
authors: Giovanni Battista
authors: 0000-0002-2597-574X
authors: GB
authors: Migliori
authors: Dept of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA Bouvé College of Health Sciences, Northeastern University, Boston, MA, USA.
authors: Meredith B
authors: MB
authors: Milstein
authors: Tomsk TB and Pulmonary Medical Center, Tomsk Oblast, Russia.
authors: Sergey P
authors: SP
authors: Mishustin
authors: Dept of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
authors: Marcello
authors: M
authors: Pagano
authors: Tropical Disease Foundation, Philippine Institute of Tuberculosis, Makati City, Philippines.
authors: Maria I
authors: MI
authors: Quelapio
authors: Lung Infection and Immunity Unit, Division of Pulmonology and UCT Lung Institute, Dept of Medicine, University of Cape Town, Cape Town, South Africa.
authors: Karen
authors: K
authors: Shean
authors: Dept of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA Partners in Health, Boston, MA, USA Brigham and Women's Hospital, Division of Global Health Equity, Boston, MA, USA Socios en Salud Sucursal, Lima, Peru.
authors: Sonya S
authors: SS
authors: Shin
authors: Dept of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
authors: Arielle W
authors: AW
authors: Tolman
authors: South African Medical Research Council, Tuberculosis Research Platform, Pretoria, South Africa.
authors: Martha L
authors: ML
authors: van der Walt
authors: Institute of Tropical Medicine, Antwerp, Belgium.
authors: Armand
authors: A
authors: Van Deun
authors: National Institute for Heath Development, Tallinn, Estonia.
authors: Piret
authors: P
authors: Viiklepp
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D060085:Coinfection; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D016016:Proportional Hazards Models; D012306:Risk; D013183:Sputum / Q000382:microbiology; D017211:Treatment Failure; D018088:Tuberculosis, Multidrug-Resistant / Q000628:therapy*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis
chemical_list: D000995:Antitubercular Agents