biostudies-literatureBoorgula GDNIAID NIH HHSNIAID102289https://www.ebi.ac.uk/biostudies/studies/S-EPMC9892238biostudies-literatureUnknown138<h4>Background</h4>There is limited high quality evidence to guide the optimal doses of drugs for the treatment of Mycobacterium kansasii pulmonary disease (Mkn-PD).<h4>Methods</h4>We performed (1) minimum inhibitory concentration experiment, (2) isoniazid dose-response study using the hollow fiber system model (HFS-Mkn) to determine PK/PD optimized exposure, and (3) another HFS-Mkn study to determine the efficacy of high dose isoniazid (15 mg/kg/day) with standard dose rifampin (10 mg/kg/day) and ethambutol (15 mg/kg/day). Inhibitory sigmoid maximal effect model and linear regression was used for data analysis.<h4>Results</h4>MIC of the 20 clinical isolates ranged between 0.5 mg/L to 32 mg/L. In the HFS-Mkn, isoniazid monotherapy failed to control the bacterial growth beyond day 7. On dayTuberculosis (Edinburgh, Scotland)Isoniazid pharmacokinetics/pharmacodynamics as monotherapy and in combination regimen in the hollow fiber system model of Mycobacterium kansasii.PMC9892238R01 AI137080R21 AI148096U01 AI150508Srivastava SHeysell SKShankar PSingh SBoorgula GDGumbo TfalseIsoniazid pharmacokinetics/pharmacodynamics as monotherapy and in combination regimen in the hollow fiber system model of Mycobacterium kansasii.<h4>Background</h4>There is limited high quality evidence to guide the optimal doses of drugs for the treatment of Mycobacterium kansasii pulmonary disease (Mkn-PD).<h4>Methods</h4>We performed (1) minimum inhibitory concentration experiment, (2) isoniazid dose-response study using the hollow fiber system model (HFS-Mkn) to determine PK/PD optimized exposure, and (3) another HFS-Mkn study to determine the efficacy of high dose isoniazid (15 mg/kg/day) with standard dose rifampin (10 mg/kg/day) and ethambutol (15 mg/kg/day). Inhibitory sigmoid maximal effect model and linear regression was used for data analysis.<h4>Results</h4>MIC of the 20 clinical isolates ranged between 0.5 mg/L to 32 mg/L. In the HFS-Mkn, isoniazid monotherapy failed to control the bacterial growth beyond day 7. On day2023-01-01T00:00:00Z2023 Jan2025-04-04T03:00:12.361Z2025-04-04T03:00:12.361ZS-EPMC98922383651285310.1016/j.tube.2022.102289