Timothy H. Holtz, MD, MPH; Maya Sternberg, PhD; Steve Kammerer, MBA; Kayla F. Laserson, ScD; Vija Riekstina, MD; Evija Zarovska, MD; Vija Skripconoka, MD; Charles D. Wells, MD; Vaira Leimane, MD
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, email@example.com.
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.
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.
To evaluate and compare time to and predictors of initial sputum culture conversion with predictors of treatment outcome for patients with multidrug-resistant TB.
Retrospective cohort study.
All civilian patients with multidrug-resistant TB treated with the DOTS-Plus strategy between 1 January and 31 December 2000.
Individualized treatment for confirmed sputum culture–positive pulmonary multidrug-resistant TB.
Time to initial sputum culture conversion and treatment outcome.
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.
Twenty-five percent of patients missed 5 or more monthly sputum collections.
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.
The accepted method for monitoring treatment of multidrug-resistant pulmonary tuberculosis is periodic sputum culture. The predictors of culture conversion to negative and their relation to final treatment outcome are not known.
Seventy-seven percent of 167 Latvian patients who were receiving DOTS for multidrug-resistant pulmonary tuberculosis had conversion to negative cultures (median time, 8 weeks). Predictors of a longer conversion time were history of treatment for multidrug-resistant tuberculosis, bilateral cavitations, and high colony count on initial sputum cultures. The final outcome was better when sputum conversion occurred within 2 months.
For multidrug-resistant pulmonary tuberculosis, DOTS can be successful in most patients.
Comparison of γ distribution survival plot versus the observed Kaplan–Meier survival curve in 167 patients.
Comparison of γ, log-normal, and Weibull distribution survival plots versus the observed Kaplan–Meier survival curve in 167 patients.
Initial sputum culture conversion in 129 of 167 culture-positive patients who had culture conversion.
Table 1. Univariate Accelerated Failure Time Estimates of Percentage Differences in Time to Initial Sputum Culture Conversion in 167 Culture-Positive Patients with Multidrug-Resistant Tuberculosis
Kaplan–Meier survival curve of time to initial sputum culture conversion versus category of previous treatment in 167 patients.P
Table 2. Multivariate Accelerated Failure Time Model Estimates of Percentage Difference in Time to Initial Sputum Culture Conversion in 166 Patients with Multidrug-Resistant Tuberculosis
Table 3. Initial Sputum Culture Conversion and Outcome of Treatment among 167 Patients with Multidrug-Resistant Tuberculosis
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Holtz TH, Sternberg M, Kammerer S, Laserson KF, Riekstina V, Zarovska E, et al. Time to Sputum Culture Conversion in Multidrug-Resistant Tuberculosis: Predictors and Relationship to Treatment Outcome. Ann Intern Med. ;144:650–659. doi: 10.7326/0003-4819-144-9-200605020-00008
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Published: Ann Intern Med. 2006;144(9):650-659.
Infectious Disease, Mycobacterial Infections, Prevention/Screening.
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