Mycobacterium tuberculosis sterilizing activity of faropenem, pyrazinamide and linezolid combination and failure to shorten the therapy duration.

Background: Faropenem (F), an orally bioavailable β-lactam, kills Mycobacterium tuberculosis (Mtb) without the help of a β-lactamase inhibitor. This study explored the sterilizing effect of adding F once or twice daily to a linezolid (L) plus pyrazinamide (Z) backbone regimen.

Methods: In vitro studies were performed using the hollow fiber model of tuberculosis (HFS-TB) to compare the kill rates of: 1) ZL two-drug combination; 2) F administered once daily plus ZL (FZL); 3) F administered twice-daily plus once daily ZL (FZL); 4) FZL with high-dose Z (FZL); 5) standard therapy of isoniazid, rifampin and Z; and 6) non-treated controls.

A 'shock and awe' thioridazine and moxifloxacin combination-based regimen for pulmonary Mycobacterium avium-intracellulare complex disease.

Objectives: To develop a thioridazine/moxifloxacin-based combination regimen for treatment of pulmonary infection due to Mycobacterium avium-intracellulare complex (MAC) that kills bacteria faster than the standard treatment regimen.

Methods: Monocytes were infected with MAC and inoculated into the hollow-fibre system model for pulmonary MAC disease (HFS-MAC). We co-administered ethambutol plus azithromycin daily for 28 days, to achieve the same human concentration-time profiles that result from standard doses, in three HFS-MAC systems.

A Long-term Co-perfused Disseminated Tuberculosis-3D Liver Hollow Fiber Model for Both Drug Efficacy and Hepatotoxicity in Babies.

Treatment of disseminated tuberculosis in children≤6years has not been optimized. The pyrazinamide-containing combination regimen used to treat disseminated tuberculosis in babies and toddlers was extrapolated from adult pulmonary tuberculosis. Due to hepatotoxicity worries, there are no dose-response studies in children.

Amikacin Pharmacokinetics/Pharmacodynamics in a Novel Hollow-Fiber Mycobacterium abscessus Disease Model.

The treatment of pulmonary Mycobacterium abscessus disease is associated with very high failure rates and easily acquired drug resistance. Amikacin is the key drug in treatment regimens, but the optimal doses are unknown. No good preclinical model exists to perform formal pharmacokinetics/pharmacodynamics experiments to determine these optimal doses.

Rapid drug tolerance and dramatic sterilizing effect of moxifloxacin monotherapy in a novel hollow-fiber model of intracellular Mycobacterium kansasii disease.

Mycobacterium kansasii is the second most common mycobacterial cause of lung disease. Standard treatment consists of rifampin, isoniazid, and ethambutol for at least 12 months after negative sputum. Thus, shorter-duration therapies are needed.