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Published ahead of print on January 6, 2003, doi:10.1164/rccm.200210-1125OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 10, May 2003, 1348-1354

A more recent version of this article appeared on May 15, 2003
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Submitted on October 4, 2002
Accepted on January 2, 2003

The bactericidal and sterilising activities of antituberculosis drugs during the first 14 days

Amina Jindani1, Caroline J Dore2, and Denis A Mitchison3*

1 Clinical Trials Programme, International Union Against Tuberculosis and Lung Disease, Paris, France, 2 MRC Clinical Trials Unit, London, United Kingdom, 3 Medical Microbiology, St. George's Hospital Medical School, London, United Kingdom

* To whom correspondence should be addressed. 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 cfu 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 sterilising 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), indicating that both drugs had important sterilising 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 antagonised the sterilising activity of other drugs.
Key words: pulmonary tuberculosis, EBA, extended EBA, bactericidal, sterilising




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