Adding Intranasal to Oral Administration of an Ultra-Rapid Near-Universal Drug Regimen Accelerates Relapse-Free Cure of Tuberculosis in Mice

We previously identified a potent 4-drug oral regimen comprising clofazimine, bedaquiline, pyrazinamide, and delamanid (parabolic response surface [PRS] regimen V) that dramatically shortens by approximately 85% the treatment duration needed to attain relapse-free cure of tuberculosis in mice compared with the standard regimen. Here, we investigated if intranasal administration of the PRS regimen V antibiotics bedaquiline and delamanid on top of the oral regimen would further accelerate tuberculosis cure in mice. We show that adding the intranasal to oral regimen further lowers lung burden of tubercle bacilli and significantly more rapidly achieves relapse-free cure. Hence, adding inhalational to oral therapy can potentially accelerate cure of tuberculosis.