Tedizolid, Faropenem, and Moxifloxacin Combination With Potential Activity Against Nonreplicating .

[] could be present in different metabolic population in the lung lesions, and nonreplicating persisters [NRP], associated with latent tuberculosis [TB], are the most difficult to kill. Test the combination of tedizolid, moxifloxacin, and faropenem for activity against NRP using SS18b in the hollow fiber model [HFS-TB]. Tedizolid and moxifloxacin were tested as, first, two-drug combination against log-phase growth [LPG] and, second, slowly replicating bacilli [SRB] under acidic condition and with faropenem to create a three-drug combination regimen. Finally, standard regimen [isoniazid-rifampin-pyrazinamide] was used as comparator in the HFS-TB experiment with NRP . HFS-TB units were sampled for drug-concentration measurement as well as for estimation of bacterial burden using solid agar and mycobacterial growth indicator tube [MGIT] method. Linear regression was used to calculate the kill slopes with each treatment regimen and analysis of variance (ANOVA) to compare the regimen. Tedizolid at standard dose in combination with high-dose moxifloxacin killed 3.05 log CFU/ml LPG and 7.37 log CFU/ml SRB in the bactericidal and sterilizing activity HFS-TB experiments, respectively. There was no statistical difference between tedizolid-moxifloxacin-faropenem combination and the standard regimen as both killed 7.35 log CFU/ml NRP in 21 days. There was no emergence of resistance to any of the drugs studied in the three HFS-TB experiments. The experimental regimen of tedizolid, moxifloxacin, and faropenem could effectively kill NRP population of , and given the efficacy against different metabolic population of could serve as a pan-TB regimen. Clinical studies are warranted to validate the findings.