Clofazimine for the treatment of Mycobacterium kansasii.

Clofazimine for the treatment of Mycobacterium kansasii.
Antimicrob Agents Chemother. 2018 May 29;:
Authors: Srivastava S, Gumbo T
Abstract
Mycobacterium kansasii pulmonary infection is global problem. Standard combination therapy consists of isoniazid 300 mg/day, rifampin 600 mg/day, and ethambutol 15 mg/kg/day for 18 months. Co-incubation of M. kansasii with different clofazimine concentrations over 7 days in test-tubes resulted in maximal kill (Emax) of 2.03 log10 CFU/mL below day 0. The concentration associated with Emax was 110 times the minimum inhibitory concentration. Next, the effect of human-like concentration-time profiles of clofazimine human-equivalent doses ranging between 0 to 200 mg daily for 21 days were examined in the intracellular-infection hollow fiber model of M. kansasii (HFS-Mkn). On day 14, when clofazimine microbial effect was maximal, the Emax was 2.57 log10 CFU/mL while dose associated with Emax was 100 mg/day. However, no dose killed M. kansasii to below day 0. 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 comparator in the HFS-Mkn On day 14, standard therapy had killed 2.32 log10 CFU/mL below day 0. The effect of standard therapy was consistent with a bi-exponential decline with kill rate constants of 1.85 per day (half-life=0.37 days) and 0.06 per day (half-life=12.7...

Source: Antimicrobial Agents and Chemotherapy - May 29, 2018 Category: Microbiology Authors: Srivastava S, Gumbo T Tags: Antimicrob Agents Chemother Source Type: research