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
Zuur, Marlanka A
Pasipanodya, Jotam G
van Soolingen, Dick
van der Werf, Tjip S
Gumbo, Tawanda
Alffenaar, Jan-Willem C
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Open Access
Type
Article
Language
en
Date of publication
2018-04-24
Year of publication
Research Projects
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Journal Issue
Title
Intermediate Susceptibility Dose-Dependent Breakpoints For High Dose Rifampicin, Isoniazid and Pyrazinamide Treatment in multidrug-resistant tuberculosis Programmes.
Translated Title
Published in
Clin Infect Dis 2018; 67(11):1743-9
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.