Isoniazid Resistance and Dosage as Treatment for Patients with Tuberculosis

Current Drug Metabolism
Simone NagelP D van Helden

Abstract

The first-line TB antibiotic isoniazid (INH) serves as a central component of combined first-line anti-tuberculosis drug therapy. However, resistance to INH has hindered the functioning of this drug. Resistance is caused by several known and unknown mutations in genes/regions in Mycobacterium tuberculosis (M. tuberculosis), followed by selection of these mutants in the presence of the drug. INH resistance can be categorised as either "high-level" (minimum inhibitory concentration (MIC) of > 1µg/mL to INH) or "low-level" (MIC between 0.1-1.0 µg/L) resistance and is dependent on the specific mutation acquired. The level of resistance is relevant, as INH resistance is often considered to be the first step in development of Multi-Drug Resistant (MDR) and extremely resistant (XDR) TB. Isoniazid is a pro-drug in which first pass metabolism happens via N-acetyltransferase and is fast, intermediate or slow, depending on the genetics of the host. Thus, low-level INH resistance, particularly in the presence of fast metabolism, could allow additional mutations, development of high-level resistance and progression to multi-drug resistance. A structured search of bibliographic databases for peer-reviewed research literature was performed. S...Continue Reading

Citations

Jul 13, 2020·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·E RivièreA Van Rie

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