Evidence of significant synergism between antibiotics and the antipsychotic, antimicrobial drug flupenthixol.

Previously, the antipsychotic, non-antibiotic compound flupenthixol dihydrochloride (Fp) was shown to exhibit distinct in vitro antibacterial activity against Gram-positive and Gram-negative bacteria and to significantly protect Swiss albino mice challenged with a known mouse virulent salmonella. The present study was designed to ascertain whether this drug could efficiently augment the action of an antibiotic or a non-antibiotic when tested in combination. A total of 12 bacterial strains belonging to various genera were selected for this study and were sensitive to the antibiotics penicillin (Pc), ampicillin, chloramphenicol, tetracycline, streptomycin, gentamicin, erythromycin, ciprofloxacin, and to the non-antibiotics methdilazine, triflupromazine, promethazine, and Fp. Pronounced and statistically significant synergism (p < 0.01) was observed when Fp was combined with Pc following the disc diffusion assay system. With the help of the checkerboard method, the fractional inhibitory concentration (FIC) index of this pair was found to be 0.375, confirming synergism. This pair of Fp+ Pc was then subjected to in vivo experiments in mice challenged with Salmonella enterica serovar Typhimurium NCTC 74. Statistical analysis of the mouse protection test suggested that this combination was highly synergistic (p < 0.001, Chi-squared analysis). Fp also revealed augmentation of its antimicrobial property when combined with streptomycin, gentamicin, ciprofloxacin, and the non-antibiotic methdilazine. The results of this study may provide alternatives for the therapy of problematic infections such as those associated with Salmonella spp.

Studies on the antimicrobial potential of the cardiovascular drug lacidipine.

The cardiovascular drug lacidipine was screened in vitro for possible antibacterial activity with respect to 389 Gram-positive and Gram-negative bacterial strains. It was noticed that most bacteria (233) failed to grow at 50-200 microg/mL concentrations of the drug. Some strains were inhibited at even lower concentrations. The bacteria could be arranged according to their decreasing order of sensitivity as follows: Staphylococcus aureus, Vibrio cholerae, Salmonella spp., Shigellae, Escherichia coli, Bacillus spp., Klebsiellae and Pseudomonas spp. Lacidipine was found to be bacteriostatic in nature against S. aureus and V cholerae. When administered to Swiss strain of white mice at doses of 30 and 60 microg/mouse, lacidipine significantly protected the animals challenged with 50 MLD of S. typhimurium NCTC 74. According to the chi-square test, the in vivo data were highly significant (p<0.001).

Antimicrobial potentiality of the thioxanthene flupenthixol through extensive in vitro and in vivo experiments.

The antipsychotic thioxanthene flupenthixol, possessing a trifluoromethyl substituent at position 2, exhibited a distinct antibacterial property against 352 strains of bacteria from 3 Gram-positive and 13 Gram-negative genera. The minimum inhibitory concentration (MIC) of flupenthixol was determined by the National Committee for Clinical Laboratory Standards agar dilution method. MICs ranged from 10-100 microg/mL in most of the strains, whilst some strains were inhibited at even lower concentrations. The mode of action of this drug was found to be bacteriostatic against Staphylococcus aureus and Vibrio cholerae. In the in vivo experiments, this drug was capable of contributing significant protection (P < 0.001) to a Swiss strain of white mice challenged with 50 median lethal dose of a mouse-virulent strain at a drug concentration of 15 microg/mouse. In addition, flupenthixol remarkably reduced the number of viable bacteria in organ homogenates and blood of mice treated with this drug.