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

Zuur, Marlanka A; Pasipanodya, Jotam G; van Soolingen, Dick; van der Werf, Tjip S; Gumbo, Tawanda; Alffenaar, Jan-Willem C

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Authors

Zuur, Marlanka A
Pasipanodya, Jotam G
van Soolingen, Dick
van der Werf, Tjip S
Gumbo, Tawanda
Alffenaar, Jan-Willem C

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Article

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Title

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

Published in

Clin Infect Dis 2018; 67(11):1743-9

Publiekssamenvatting

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.