Time to Sputum Culture Conversion in Multidrug-Resistant Tuberculosis: Predictors and Relationship to Treatment Outcome

Time to Sputum Culture Conversion in Multidrug-Resistant Tuberculosis: Predictors and Relationship to Treatment Outcome

From Centers for Disease Control and Prevention, Atlanta, Georgia, and the State Agency of Tuberculosis and Lung Diseases, Riga, Latvia.

Abstract

Background: Conversion of sputum mycobacterial cultures from positive growth to negative growth of Mycobacterium tuberculosis in patients with pulmonary tuberculosis (TB) is considered the most important interim indicator of the efficacy of anti-TB pharmacologic treatment for multidrug-resistant disease.

Objective: To evaluate and compare time to and predictors of initial sputum culture conversion with predictors of treatment outcome for patients with multidrug-resistant TB.

Design: Retrospective cohort study.

Setting: Latvia.

Patients: All civilian patients with multidrug-resistant TB treated with the DOTS-Plus strategy between 1 January and 31 December 2000.

Intervention: Individualized treatment for confirmed sputum culture–positive pulmonary multidrug-resistant TB.

Measurements: Time to initial sputum culture conversion and treatment outcome.

Results: Among 167 patients who were sputum culture–positive at initiation of second-line therapy, 129 (77%) converted in a median time of 60 days (range, 4 to 462 days) and 38 (23%) did not convert. Independent predictors of a longer sputum culture conversion time, using an accelerated failure time regression model, included previous treatment for multidrug-resistant TB, high initial sputum culture colony count, bilateral cavitations on chest radiography, and the number of drugs the initial isolate was resistant to at treatment initiation. Treatment outcomes were statistically significantly worse for patients who did not convert their sputum culture within 2 months.

Limitations: Twenty-five percent of patients missed 5 or more monthly sputum collections.

Conclusions: Under program conditions in Latvia, most patients with multidrug-resistant TB achieved sputum culture conversion within 12 weeks of starting treatment. Chest radiography and sputum culture drug susceptibility testing can assist physicians in predicting which patients will convert more slowly. Sputum culture conversion is a useful and appropriate interim indicator of treatment outcome in patients with multidrug-resistant TB.

Article and Author Information

Acknowledgments: The authors thank Nong Shang, Michael Iademarco, and Kenneth Castro for their insightful comments during the preparation of this manuscript, and Carole Mitnick for her epidemiologic inspiration and critical review of the manuscript.
Grant Support: By the United States Agency for International Development (USAID), through the Centers for Disease Control and Prevention Cooperative Agreement U23 CCU021873.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Timothy H. Holtz, MD, MPH, Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS E-10, Atlanta, GA 30333, e-mail, tholtz{at}cdc.gov.
Current Author Addresses: Drs. Holtz, Laserson, and Wells and Mr. Kammerer: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS E-10, Atlanta, GA 30333.
Dr. Sternberg: Division of Sexually Transmitted Disease Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS E-63, Atlanta, GA 30333.
Drs. Riekstina, Zarovska, Skripconoka, and Leimane: State Agency of Tuberculosis and Lung Diseases, P.O. Cekule, stopinu p., Riga Region, LV-2118, Latvia.
Author Contributions: Conception and design: T.H. Holtz, M. Sternberg, S. Kammerer, K.F. Laserson, C.D. Wells, V. Leimane.
Analysis and interpretation of the data: T.H. Holtz, M. Sternberg, S. Kammerer, K.F. Laserson.
Drafting of the article: T.H. Holtz, K.F. Laserson.
Critical revision of the article for important intellectual content: M. Sternberg, S. Kammerer, V. Riekstina, E. Zarovska, V. Skripconoka, C.D. Wells, V. Leimane.
Statistical expertise: T.H. Holtz, M. Sternberg, S. Kammerer, K.F. Laserson.
Administrative, technical, or logistic support: V. Riekstina, E. Zarovska, V. Skripconoka, C.D. Wells, V. Leimane.
Collection and assembly of data: V. Riekstina, E. Zarovska, V. Skripconoka.