Antimicrobial agents and chemotherapy
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Antimicrob. Agents Chemother. · Jan 2015
Randomized Controlled TrialImpact of nonlinear interactions of pharmacokinetics and MICs on sputum bacillary kill rates as a marker of sterilizing effect in tuberculosis.
The relationships between antituberculosis drug exposure and treatment effects on humans receiving multidrug therapy are complex and nonlinear. In patients on treatment, an analysis of the rate of decline in the sputum bacillary burden reveals two slopes. The first is the α-slope, which is thought to reflect bactericidal effect, followed by a β-slope, which is thought to reflect sterilizing activity. ⋯ However, isoniazid and ethambutol exposures may only be of importance when rifampin exposure is low. These findings need confirmation in larger studies. (This study has been registered at controlled-trials.com under registration no. ISRCTN80852505.).