Clofazimine for the Treatment of Mycobacterium kansasii

Antimicrobial Agents and Chemotherapy
Shashikant Srivastava, Tawanda Gumbo

Abstract

Mycobacterium kansasii pulmonary infection is a global problem. Standard combination therapy consists of isoniazid at 300 mg/day, rifampin at 600 mg/day, and ethambutol at 15 mg/kg of body weight/day for 18 months. Coincubation of M. kansasii with different clofazimine concentrations over 7 days in test tubes resulted in a maximal kill (maximum effect [Emax]) of 2.03 log10 CFU/ml below the day 0 bacterial burden. The concentration associated with Emax was 110 times the MIC. Next, the effects of human-like concentration-time profiles of clofazimine human-equivalent doses ranging from 0 to 200 mg daily for 21 days were examined in the hollow-fiber model of intracellular M. kansasii (HFS-Mkn). On day 14, when the clofazimine microbial effect was maximal, the Emax was 2.57 log10 CFU/ml, while the dose associated with Emax was 100 mg/day. However, no dose killed M. kansasii to levels below the day 0 bacterial burden. Thus, the antimicrobial effect of clofazimine monotherapy in the HFS-Mkn was modest. Human-equivalent concentration-time profiles of standard combination therapy and doses were used as comparators in the HFS-Mkn On day 14, standard therapy killed to a level 2.32 log10 CFU/ml below the day 0 bacterial burden. The effect ...Continue Reading

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Nov 29, 2017·Antimicrobial Agents and Chemotherapy·Devyani DeshpandeTawanda Gumbo

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Citations

Mar 24, 2020·Expert Opinion on Pharmacotherapy·Maria-Carmen Muñoz-EgeaJaime Esteban
Oct 16, 2018·Frontiers in Microbiology·Michelle S DeStefanoMichael H Cynamon
Feb 10, 2021·Antimicrobial Agents and Chemotherapy·Shashikant SrivastavaTawanda Gumbo
Jul 16, 2021·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Miriama CeresnakovaSarah P Hudson
Dec 22, 2021·Journal of Global Antimicrobial Resistance·Shashikant SrivastavaJulie V Philley

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