Antimicrobial effects of nonantibiotics – reversal of resistance in Gram-positive bacteria

Abstract number: 1134_01_75

Hendricks O., Aagaard L., Christensen J.B., Skov M.N., Kolmos H.J., Kristiansen J.E.

Objectives:  

The project investigates the antimicrobial activity of defined non-antibiotics against clinically relevant gram positive bacteria and the interaction of these compounds with antibiotics.Growing problems with antibiotic resistance have increased the need for alternative antimicrobial treatment strategies. Psychotropic therapeutics, especially the phenothiazines,have antimicrobial activities and may reverse antibiotic resistance in vitro (1). Such agents could be used as helper-compounds to antibiotics.

Methods:  

The Minimum Inhibitory Concentration (MIC) of each antibiotic against various strains employed in this study was determined by the E-test system and checkerboard microdilution techniques. MICs for all non-antibiotic test substances were determined by agar- dilution. The interaction of each antibiotic with the test substances was determined by the checkerboard method and interpretation of synergy, additive or interference effects was recorded.

Results:  

We found that all Gram-positive bacterial strains, regardless of their susceptibility to regularly used antibiotics, were inhibited by the test substances at concentrations of 8–128 mg/ ml. In case of sertraline, racemic and stero-isomeric forms of thioridazine MIC levels at 8–32 mg/ ml were defined. Furthermore, racemic and stereo-isomeric forms of thioridazine are characterized by resistance modifying abilities at subinhibitory concentrations. The study showed up to 256- fold reduction of primarily defined MIC values of different antibiotics such as oxacillin, erytromycin, vancomycin and ampicillin for different Gram positive species (2). The concentrations used in synergy studies are comparable to those found in body tissues after therapeutically application of chlorpromazine.

Conclusion:  

Since many of the classical narcoleptics are known to be mixtures of stereoisomers, the challenge for the future is screening the pure isomers for reduced central nervous system activity and maintained antibiotic potential and especially use the CNS inactive stereoisomeres as ''helper-compounds'' utilizing their potentials as antimicrobial resistant reversal agents of Gram positive organisms.

Literature

1. Kristiansen JE. The antimicrobial activity of psychotropic drugs and stereo isomeric-analogues (disp)Dan Med Bull 1990; 37:165–82. 2. Hendricks O et al. Antibakterielle Eigenschaften der Phenothiazine–eine Behandlungoption für die Zukunft? Chemother J 2004; 13: 203–205.