Time to culture conversion and regimen composition in multidrug-resistant tuberculosis treatment

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-tuberculos...

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Bibliographic Details
Published in:PloS one 2014-09, Vol.9 (9), p.e108035-e108035
Main Authors: Tierney, Dylan B, Franke, Molly F, Becerra, Mercedes C, Alcántara Virú, Félix A, Bonilla, César A, Sánchez, Epifanio, Guerra, Dalia, Muñoz, Maribel, Llaro, Karim, Palacios, Eda, Mestanza, Lorena, Hurtado, Rocío M, Furin, Jennifer J, Shin, Sonya, Mitnick, Carole D
Format: Article
Language:English
Subjects:
Adult
Analysis
Antitubercular Agents - administration & dosage
Antitubercular Agents - therapeutic use
Clinical Protocols
Clinical trials
Composition effects
Conversion
Culture
Disease
Drug therapy
Drugs
Exposure
Female
Hazards
Health aspects
Health risk assessment
HIV
Hospitals
Human immunodeficiency virus
Humans
Male
Medical research
Medicine and Health Sciences
Microbial drug resistance
Multidrug resistance
Multidrug resistant organisms
Patients
Proportional Hazards Models
Retrospective Studies
Sputum
Tachycardia
Time Factors
Tuberculosis
Tuberculosis, Multidrug-Resistant - diagnosis
Tuberculosis, Multidrug-Resistant - drug therapy
Viruses
Womens health
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0108035