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.
Highlights
Antibiotics are the most imperative weapons in combating bacterial infections, over the past few decades the use of antibiotics is becoming increasingly restricted
The susceptibility of 50 K. pneumoniae isolates to each of 16 antimicrobial agents was determined by agar dilution method
It was found that the tested phenothiazine antihistaminic, promethazine, and cyproheptadine were the most effective among the studied antihistaminics
Summary
Antibiotics are the most imperative weapons in combating bacterial infections, over the past few decades the use of antibiotics is becoming increasingly restricted. There is evidence in the literature that certain non-antibiotic compounds, alone or in combination with conventional antibiotics, may play a useful role in the management of specific bacterial infections associated with a high risk of resistance to conventional antibiotics [4,5]. Examples of these non-antibiotic drugs, antihistaminics, mucolytics, local anaesthetics, antihypertensive drugs, anti-depressants and anticoagulants. Other studies found that these drugs may decrease antibacterial activity of different antibiotics
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