Sertraline enhances bacterial control by improving the pharmacodynamic -pharmacokinetic properties of frontline TB drugs

Given the need for innovative interventions for tackling the burden of TB, host directed therapies have emerged as a promising alternative in recent times. The combination of sertraline with frontline TB drugs has shown excellent promise in the murine models of infection in imparting better bacterial control and increasing host survival. We tested if the addition of sertraline worked to increase bacterial clearance in the random bred guinea pig model of TB infection that mimics the inter individual heterogeneity observed in the human response to infection. The combination of sertraline and frontline TB drugs effectively reduced bacterial burdens in the tissues of guinea pigs significantly better than the drugs alone with a marked betterment of lung histopathology. In order to evaluate the effect of sertraline on the pharmacodynamic properties of TB drugs, concentrations of the drugs were estimated in tissues at different time intervals over a period of 24h of administration to rats. Overall, addition of sertraline did not alter TB drug distribution or clearance from the animals, although enriching drug amounts transiently between 3-6 h in the different tissues. We thus highlight the advantage of an adjunct TB therapy with the inclusion of sertraline, an FDA approved antidepressant, in improving the PKPD of TB drugs and imparting better infection control in diverse models of infection.