Comparison of a novel regimen of rifapentine, tedizolid, and minocycline with standard regimens for treatment of the pulmonary Mycobacterium kansasii.

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Comparison of a novel regimen of rifapentine, tedizolid, and minocycline with standard regimens for treatment of the pulmonary Mycobacterium kansasii.

Antimicrob Agents Chemother. 2020 Jul 20;:

Authors: Chapagain M, Gumbo T, Heysell SK, Srivastava S

Abstract
The combination of isoniazid, rifampin and ethambutol, is recommended by the American Thoracic Society (ATS) for treatment of pulmonary Mycobacterium kansasii (Mkn) while the British Thoracic Society (BTS) recommends clarithromycin, rifampin and ethambutol. Unfortunately, therapy duration for both regimens lasts for years. Here, we administered tedizolid, minocycline, clarithromycin, and rifapentine, as monotherapy as well as novel combinations in the intracellular hollow fiber model system of Mkn (HFS-Mkn) in a 28 days study. The ATS and BTS regimens were used as comparator. Repetitive sampling was used to validate the intended intrapulmonary pharmacokinetics of each drug and to monitor changes in Mkn burden. As monotherapy, at observed tedizolid AUC0-24/MIC of 5.85 and minocycline AUC0-24/MIC of 5.77 failed to kill the bacteria below day 0 [stasis], clarithromycin AUC0-24/MIC of 2.4 held the bacterial burden at stasis, but the rifapentine AUC0-24/MIC of 140 killed 2 log10 cfu/mL below stasis. The BTS regimen kill slope was -0.083±0.035 cfu/mL/day which was significantly superior to the ATS regimen slope of -0.038±0.038 cfu/mL/day. The rifapentine-tedizolid-minocycline combination kill slope was -0.119±0.031 cfu/mL/day, superior to the ATS regimen and comparable with the BTS regimen.Summary Statement. BTS and the novel rifapentine-tedizolid-minocycline regimen showed better kill of intracellular bacteria in the HFS-Mkn However, the efficacy of the new combination regimen remains to be tested in clinical settings.

PMID: 32690646 [PubMed - as supplied by publisher]