An Evaluation of the Antibacterial Activities of Combinations of Sulfonamides, Trimethoprim, Dibromopropamidine, and Silver Nitrate Compared with Their Uptakes by Selected Bacteria

• Published in: Journal of pharmaceutical sciences 1991-09, Vol.80 (9), p.861-867
• Main Authors: Richards, R. Michael E., Taylor, Robert B., Xing, Dorothy K.L.
• Format: Article
• Language: English
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteria - drug effects; Bacteria - metabolism; Benzamidines - administration & dosage; Benzamidines - pharmacokinetics; Benzamidines - pharmacology; Biological and medical sciences; Drug Combinations; Drug Synergism; Enterobacter cloacae; Enterobacter cloacae - drug effects; Enterobacter cloacae - metabolism; Leucovorin - pharmacology; Medical sciences; Pharmacology. Drug treatments; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - metabolism; Silver Nitrate - administration & dosage; Silver Nitrate - pharmacokinetics; Silver Nitrate - pharmacology; Staphylococcus aureus - drug effects; Staphylococcus aureus - metabolism; Sulfonamides - administration & dosage; Sulfonamides - pharmacokinetics; Sulfonamides - pharmacology; Trimethoprim - administration & dosage; Trimethoprim - pharmacokinetics; Trimethoprim - pharmacology
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600800912

Modifications of antibacterial activity have been demonstrated using combinations of two antibacterials from trimethoprim, sulfonamides (sulfadiazine, sulfamerazine, and silver sulfadiazine), silver nitrate, and dibromopropamidine isethionate, either formulated in a cream base or dissolved in peptone water. The creams were evaluated using the agar cup diffusion method in isosensitest agar. The peptone water solutions provided fractional inhibitory concentrations for combinations of the antibacterial substances. The test organisms were Pseudomonas aeruginosa, Enterobacter cloacae, and Staphylococcus aureus Bacterial uptakes of antibacterial combinations, determined by either an HPLC assay method or an atomic absorption method, combined with dry cell weight determinations, indicated that enhancement of activity of the antibacterial combinations against P. aeruginosa (two strains) and E. cloacae were related to marked increases in the bacterial uptake of the chemical agents. Decreases in activity were related to decreased uptake of either dibromopropamidine and/or silver ions. The effect of the trimethoprim and the sulfonamides was shown to depend on their effect on bacterial folate synthesis. It is suggested that partial blockade of the folate synthetic pathway leads to an effect on cell permeability which results in increased uptake of antibacterials. Dibromopropamidine isethionate also has an effect on cell permeability which produces an increased bacterial uptake of a second antibacterial present in the medium. These findings provide further explanation of how subinhibitory concentrations of trimethoprim and sulfonamide combinations are synergistic against a wide range of bacteria even when certain bacteria are resistant to either member of the combination.