Modulation of Antibiotic Efficacy against Klebsiella pneumoniae by Antihistaminic Drugs

Abstract

Antihistaminic drugs are widely used for various indications during microbial infection. Hence, this paper has investigated the antibacterial activity of seven antihistaminic drugs belonging to both old and new generations against multiresistant K. pneumonia isolates. The bacteriostatic activity of these tested drugs was investigated by determining their MIC by agar dilution technique against thirty multiresistant K. pneumoniae isolates. Two drugs namely promethazine, cyproheptadine showed antibacterial activity against the tested K. pneumoniae isolates with MIC values rangining from 400-1000 μg/ml (far more than their biological levels). In contrast, other tested drugs showed no in-vitro antibacterial activity under the conditions of test. Investigation of the interaction between the tested drugs and different antibiotics against multiresistant K. pneumoniae isolates revealed that synergism was major in case of combination with macrolides, aminoglycosides and quinolones especially with promethazine, cyproheptadine, cetirizine and diphenhydramine. The effect of tested drugs on antibiotic efflux by the tested isolates was also investigated. It was observed that promethazine and cyproheptadine were the most effective efflux pump inhibitor at a concentration of 100 μg/ml. Upon studying the effect of tested drugs on biofilm formation by K. pneumoniae, it was found that promethazine was the most effective inhibitor of biofilm formation. It reduced biofilm formation by K. pneumoniae in a concentration-dependent manner and prevented biofilm formation at a concentration of 100 μg/ml. In the present study, it was found that the use of 100 μg/ml chlorpheniramine resulted in the conversion of separate rod shape of K. pneumoniae cells into long filaments. This was confirmed by transmission electron microscope where septum formation with no separation was recorded. In conclusion, the data obtained in this work showed that, among the tested drugs promethazine and cyproheptadine exerted high antibacterial activity against MDR K. pneumoniae isolates. So, it is possible to take the advantages of the obtained findings to introduce new ways to overcome different infectious diseases.