Intermediate Susceptibility Dose-Dependent Breakpoints For High Dose Rifampicin, Isoniazid and Pyrazinamide Treatment in multidrug-resistant tuberculosis Programmes.

Abstract

In infectious diseases, for some drugs, bacterial susceptibility is categorized as susceptible, intermediate-susceptible dose-dependent (ISDD), and resistant. The strategy is to use higher doses of first-line agents in the ISDD category, thereby preserving the use of these drugs. This system has not been applied to anti-tuberculosis drugs. Pharmacokinetics/pharmacodynamics (PK/PD) target exposures, in tandem with Monte Carlo experiments (MCE), recently identified susceptibility breakpoints of 0.0312 mg/L for isoniazid, 0.0625 mg/L for rifampicin, and 50 mg/L for pyrazinamide. These have been confirmed in clinical studies.