EXPERIMENTAL EVALUATION OF SYNERGISTIC ACTION BETWEEN ANTIBIOTICS AND THE ANTIPSYCHOTIC ANTIMICROBIAL TRIFLUPROMAZINE

Abstract

Significant antimicrobial action of the antipsychotic drug triflupromazine (Tp) against various genera of bacteria has been evaluated extensively in previous studies. This present investigation was designed to study whether this phenothiazine is able to augment action of an antibiotic when tested in combination. A total of twelve different bacterial strains belonging to various genera were used and tested to be sen- sitive against many antibiotics and the non antibiotic Tp. The Minimum inhibitory concentration (MIC) of all the test bacteria with respect to the antibiotics ranged fron 2- 50 µg/ml. In case of Tp, MIC ranged from 25-200 µg/ml. Disc diffusion assays revealed synergism between Tp and penicillin, ampicillin, carbenicillin, streptomycin (Sm), gentamicin and ciprofloxacin. Antagonistic effect was shown between Tp and cloxacillin, erythromycin and tetracyclin. Most effective and statistically significant (p<0.001) synergism was observed when Tp was combined with Sm. Following checkerboard method, the Fractional inhibitory concentration (FIC) index of the duo was determined to be 0.375, which confirmed significant synergism. The pair when subjected to in vivo experiments in mice challenged with Salmonella enterica serovar Typhimurium NCTC 74, showed statistically significant (p<0.001) mouse protection and also resulted in reduction of the infection in internal organs. This further suggests the pair to be highly synergistic. Thus, from this study it can be concluded that the antimicrobial activity of the non antibiotic Tp can be further remarkably increased in combination with a suitable antibiotic to combat against multi drug resistant bacteria and can be used effectively as an alternative therapy.