Reversal of antibiotic resistance in Gram-positive bacteria by the antihistaminic azelastine

Abstract

Antibiotic resistance represents a serious problem that complicates microbial infection. The use of 'helper compounds' capable of enhancing the antimicrobial activity of antibiotics is being investigated. Azelastine, a new generation antihistaminic, possesses certain antibacterial activity and is capable of inducing alteration in the bacterial membrane permeability. Hence, we hypothesized that it could reverse resistance to antibiotics. Azelastine significantly increased the antibacterial activity of eight antibiotics belonging to five different classes (β-lactams, macrolides, fluoroquinolones, aminoglycosides and tetracyclines) against nine Gram-positive clinical isolates: five Staphylococcus aureus, two Staphylococcus epidermidis and two Enterococcus faecium, seven of which were multi-drug resistant, reversing their resistance to the tested antibiotics. The synergistic effects of azelastine with the studied antibiotics increased with raising the pH from 5 to 8. Antibiotics did not affect the ability of azelastine to alter the permeability of a liposomal artificial membrane model, an effect thought to be critical for the interaction with antibiotics. The findings of this study present azelastine as a potential 'helper compound' that could reverse the resistance of multi-drug resistant Gram-positive clinical isolates to antibiotics.