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

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