Evaluation of In Vivo and In Vitro Antimicrobial Activities of a Selective Serotonin Reuptake Inhibitor Sertraline Hydrochloride

Amalesh      Samanta; Debprasad      Chattopadhyay; Chandrima      Sinha; Ananda      Dulal Jana; Soma      Ghosh; Anurup      Mandal; Ananya      Banerjee; Oliver      Hendricks; Jorn      B. Christensen; Jette      Elisabeth Kristiansen

Abstract

We investigated the in vitro and in vivo antimicrobial potential of a selective serotonin reuptake inhibitor sertraline hydrochloride, against clinical isolates of bacteria and Candida species. Minimum Inhibitory Concentration of sertraline against 161 human isolates of 12 Gram negative and 5 Gram positive genera, Candida albicans ATCC10231 and Candida tropicalis ATCC13803 was determined by spot inoculation, broth and agar dilution methods along with its postantibiotic effect following a short drug exposure. The toxicity and protective efficacy was tested in vivo with a mousevirulent strain of Salmonella typhimurium NCTC74.The MIC was 20-200μg/ml for bacteria, and 200μg/ml for Candida. The growth inhibitory study with Bacillus subtilis UC564 and Shigella dysenteriae NCTC599/52 revealed that the drug is bacteriostatic at its MIC and cidal at higher concentrations. Study on its post-antibiotic effect following a short drug exposure revealed that Sertraline has a time- and dose-dependent effect. Treatment for 4h at concentrations below and equipotent to the minimal static concentration resulted in a lag of regrowth at 8-24h for Candida isolates. The in vivo study with Salmonella typhimurium in Swiss mice showed that the median lethal dose was 1.9 x 107 cfu and 50 LD50 was 0.95x109. Interestingly, the drug at a non-toxic single dose provides significant protection (P<0.001) to the mice challenged with S. typhimurium. Sertraline remarkably reduced the number of viable bacteria in organ homogenates and blood of the treated animals and demonstrate both in vitro and in vivo antibacterial potential at lower dose than its predesignated pharmacological activity.

Keywords: Sertraline hydrochloride, SSRI, antibacterial activity, antifungal activity, non-antibiotic