Published ahead of print on January 6, 2003, doi:10.1164/rccm.200210-1125OC
American Journal of Respiratory and Critical Care Medicine Vol 167. pp. 1348-1354, (2003)
© 2003 American Thoracic Society
Bactericidal and Sterilizing Activities of Antituberculosis Drugs during the First 14 Days
Amina Jindani,
Caroline J. Doré and
Denis A. Mitchison
Clinical Trials Program, International Union Against Tuberculosis and Lung Disease, Paris, France; Medical Research Council Clinical Trials Unit; and Department of Medical Microbiology, St George's Hospital Medical School, London, United Kingdom
Correspondence and requests for reprints should be addressed to Denis A. Mitchison, M.D., Department of Medical Microbiology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. E-mail: dmitchis{at}sghms.ac.uk
Colony-forming units of Mycobacterium tuberculosis in sputum were counted at 2-day intervals in 100 patients treated with 22 regimens of isoniazid, rifampin, pyrazinamide, ethambutol, or streptomycin, given alone or in combinations. The exponential fall in colony-forming units was measured by linear regression coefficients of the log counts during the initial 2-day phase of rapid, drug-determined killing and during the subsequent 12 days of much slower sterilizing activity. The regression coefficients during the first 2 days varied significantly according to the drug; the greatest effects in multiple regression analyses were due to isoniazid (p < 0.001) and rifampin (p = 0.027). The rapid kill obtained with isoniazid was unaffected by addition of other drugs, so that a change in activity after adding an unknown drug to isoniazid would not be measurable. In multiple regression analysis of the coefficients during Days 2–14, rifampin and streptomycin had significant effects (p = 0.007 and 0.006, respectively), indicating that both drugs had important sterilizing activity, streptomycin particularly early. Isoniazid and pyrazinamide had no significant effects. In analyses of combined drug regimens only, ethambutol had an effect (p = 0.01) in reverse direction to that of rifampin, suggesting it antagonized the sterilizing activity of other drugs.
Key Words: bactericidal • early bactericidal activity • extended early bactericidal activity • pulmonary tuberculosis • sterilizing
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