title: Time to culture conversion and regimen composition in multidrug-resistant tuberculosis treatment.
abstract: Sputum cultures are an important tool in monitoring the response to tuberculosis treatment, especially in multidrug-resistant tuberculosis. There has, however, been little study of the effect of treatment regimen composition on culture conversion. Well-designed clinical trials of new anti-tuberculosis drugs require this information to establish optimized background regimens for comparison. We conducted a retrospective cohort study to assess whether the use of an aggressive multidrug-resistant tuberculosis regimen was associated with more rapid sputum culture conversion. We conducted Cox proportional-hazards analyses to examine the relationship between receipt of an aggressive regimen for the 14 prior consecutive days and sputum culture conversion. Sputum culture conversion was achieved in 519 (87.7%) of the 592 patients studied. Among patients who had sputum culture conversion, the median time to conversion was 59 days (IQR: 31-92). In 480 patients (92.5% of those with conversion), conversion occurred within the first six months of treatment. Exposure to an aggressive regimen was independently associated with sputum culture conversion during the first six months of treatment (HR: 1.36; 95% CI: 1.10, 1.69). Infection with human immunodeficiency virus (HR 3.36; 95% CI: 1.47, 7.72) and receiving less exposure to tuberculosis treatment prior to the individualized multidrug-resistant tuberculosis regimen (HR: 1.58; 95% CI: 1.28, 1.95) were also independently positively associated with conversion. Tachycardia (HR: 0.77; 95% CI: 0.61, 0.98) and respiratory difficulty (HR: 0.78; 95% CI: 0.62, 0.97) were independently associated with a lower rate of conversion. This study is the first demonstrating that the composition of the multidrug-resistant tuberculosis treatment regimen influences the time to culture conversion. These results support the use of an aggressive regimen as the optimized background regimen in trials of new anti-TB drugs.
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Partners In Health, Boston, Massachusetts, United States of America; Socios En Salud Sucursal Peru, Lima, Peru.
authors.forename: Dylan B
authors.initials: DB
authors.lastname: Tierney
authors.affiliation: Partners In Health, Boston, Massachusetts, United States of America; Socios En Salud Sucursal Peru, Lima, Peru; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Molly F
authors.initials: MF
authors.lastname: Franke
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Partners In Health, Boston, Massachusetts, United States of America; Socios En Salud Sucursal Peru, Lima, Peru; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Mercedes C
authors.initials: MC
authors.lastname: Becerra
authors.affiliation: Partners In Health, Boston, Massachusetts, United States of America; Socios En Salud Sucursal Peru, Lima, Peru.
authors.forename: Félix A
authors.initials: FA
authors.lastname: Alcántara Virú
authors.affiliation: National Tuberculosis Strategy, Ministry of Health, Lima, Peru.
authors.forename: César A
authors.initials: CA
authors.lastname: Bonilla
authors.affiliation: Hospital Nacional Sergio E. Bernales, Lima, Peru.
authors.forename: Epifanio
authors.initials: E
authors.lastname: Sánchez
authors.affiliation: Partners In Health, Boston, Massachusetts, United States of America; Socios En Salud Sucursal Peru, Lima, Peru.
authors.forename: Dalia
authors.initials: D
authors.lastname: Guerra
authors.affiliation: Partners In Health, Boston, Massachusetts, United States of America; Socios En Salud Sucursal Peru, Lima, Peru.
authors.forename: Maribel
authors.initials: M
authors.lastname: Muñoz
authors.affiliation: Partners In Health, Boston, Massachusetts, United States of America; Socios En Salud Sucursal Peru, Lima, Peru.
authors.forename: Karim
authors.initials: K
authors.lastname: Llaro
authors.affiliation: Asociacion Visionarios, Peru, Lima, Peru.
authors.forename: Eda
authors.initials: E
authors.lastname: Palacios
authors.affiliation: Asociacion Visionarios, Peru, Lima, Peru.
authors.forename: Lorena
authors.initials: L
authors.lastname: Mestanza
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Global Health Committee, Boston, Massachusetts, United States of America.
authors.forename: Rocío M
authors.initials: RM
authors.lastname: Hurtado
authors.affiliation: Tuberculosis Research Unit, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Furin
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Partners In Health, Boston, Massachusetts, United States of America; Socios En Salud Sucursal Peru, Lima, Peru.
authors.forename: Sonya
authors.initials: S
authors.lastname: Shin
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, United States of America; Partners In Health, Boston, Massachusetts, United States of America; Socios En Salud Sucursal Peru, Lima, Peru; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Carole D
authors.initials: CD
authors.lastname: Mitnick
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002985:Clinical Protocols; D005260:Female; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents