Antimicrobial effects of non-antibiotics on resistant Gram-positive bacteria

Abstract number: 1733_197

Hendricks O., Butterworth T., Christensen J., Sahly H., Podschun R., Kristiansen J.

Objectives: Psychotropic therapeutics, especially the phenothiazines are employed for the treatment of psychosis though they exhibit the additional property of an anti-microbial activity. We defined MICs for selected compounds on clinically relevante Gram-positive bacteria. The evaluation of the combined effect of these compounds and conventional antibiotics of clinical relevance showed a significant synergistic effect. As intracellular survival of Gram positive species is another possible explanation for the insufficiency of antibiotic treatment, we investigated the influence of phenothiazines on bacterial invasion in human epithelial cell lines. The project investigates the anti-microbial activity of Non-antibiotics against clinically relevant Gram-positiv bacteria, e.g. staphylococci, streptococci and enterococci.

Methods: Agardilution, Microdilution, Human ephitelcell-models A-549, HCT-8, T-24.

Results: All Gram-positive bacterial strains, regardless of their susceptibility to regularly used antibiotics, were inhibited by the testsubstances at concentrations of 8–64 g/L. Combination of the antibiotics and the choosen testcompounds at subinhibitory concentration demonstrated a restored activity for the investigated antibiotics. We documented interference of our test-compounds with efflux based multidrug resistance. Furthermore, we recorded a significant reduction of the mean bacterial invasion ability in the investigated cell lines in the presence of selected agents. Overall, these results indicated a significant reduction of the mean invasion ability of the Gram-positive bacteria in all epithelial cell lines (18.9%±1.8) as compared to the invasion in absence of the substance (52.1%±4.4) (p < 0.0001).

Conclusions: The present experiment shows that phenothiazine derivates, especially thioridazine, have an antimicrobial effect against the investigated strains. Our studies offer new information on the effect of phenothiazines on Resistant Gram-positive bacteria. The anti-microbial activity of these compounds may have a place in the treatment of infections where the possibilities for current antibiotic treatment are limited.