Antimicrobial Activity of a Series of 1-Alkyl-2-(4-Pyridyl)Pyridinium Bromides against Gram-Positive and Gram-Negative Bacteria

Objective: To test a series of 1-alkyl-2-(4-pyridyl)pyridinium bromides with alkyl chains containing between 9 and 16 carbons against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Stenotrophomonas maltophilia, Acinetobacter baumannii and Pseudomonas aeruginosa) bacteria. Materials and Methods: Chemical synthesis was based on the reaction of 2,4′-bipyridyl with alkyl bromide. Antimicrobial activity of the bipyridyls was measured by growing bacterial cultures on Mueller-Hinton agar in the presence and absence of inhibitors. Results:The compounds were most active against S. aureus. The most active compounds had alkyl chain lengths of between 11 and 16 carbons. Methicillin-sensitive S. aureus was more susceptible to the inhibitors than methicillin-resistant S. aureus (MRSA). Two subclasses of MRSA existed which differed in their susceptibility to the inhibitors. The susceptibility of MRSA strains to the compounds was increased in the presence of the efflux pump inhibitor reserpine. The activity of the compounds against Gram-negative organisms was increased when the membrane-permeabilizing agent sodium citrate was introduced. Critical micelle concentrations of the compounds were much higher than minimum inhibitory concentrations of the inhibitors. Conclusion: The mechanism of action of the compounds may involve perturbing bacterial membranes. The resistance of some MRSA strains to the compounds may be related to efflux pumps.