Synergistic activity of weak organic acids against uropathogens

Abstract

Urinary tract infections (UTIs) are among the most common hospital-acquired infections, with an estimated 75% of UTIs caused by urinary catheters. In addition to the significant healthcare costs and patient morbidity, the escalating antimicrobial resistance reported among common uropathogens make the investigation of efficacious new antimicrobial strategies of urgent importance. To examine the antibacterial activity of a suite of weak organic acids (WOAs) (citric acid, malic acid, propionic acid, mandelic acid, lactic acid, benzoic acid, pyruvic acid and hippuric acid), alone and in combination, against common nosocomial uropathogens (Proteus mirabilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa). Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm eradication concentration (MBEC), fractional inhibitory concentration index (FICI) values and kinetics of bactericidal activity of WOAs were determined by microdilution and time-kill assays. All tested WOAs displayed bactericidal activities against uropathogens in their planktonic and biofilm modes of growth when used individually. Moreover, WOAs in combination displayed synergistic activity against P.mirabilis, S. aureus and E.coli, with reductions in MIC values of up to 250-fold and significant reductions in biofilm formation. The synergistic multi-mechanistic combinations identified herein are anticipated to play an important role in the treatment and prevention of catheter-associated UTIs.