Weak organic acid synergy towards the prevention of catheter blockages.

BACKGROUND: Up to 50% of all long-term catheterized individuals experience recurrent episodes of urinary catheter infections and blockages, leading to urine retention, pyelonephritis and septicaemia if the catheter is left in situ. We have previously reported the synergistic activity of weak organic acid (WOA) combinations against nosocomial uropathogens. AIM: To investigate the efficacy of selected WOAs, citric acid and propionic acid, alone and in combination, on prevention of crystalline biofilm formation and catheter blockages. METHODS: Static crystallization assays and dynamic in vitro bladder model assays, with scanning electron microscopy, were performed for determination of bacterial viability, urinary pH and time to catheter blockage. FINDINGS: The rate of encrustation around the catheter eyeholes was reduced in the presence of the citric acid/propionic acid combination, extending the time to blockage three-fold. CONCLUSION: Synergistic WOA combinations identified herein represent promising alternatives to antibiotics to combat the global healthcare burden of catheter-associated urinary tract infections and related blockages.

Synergistic activity of weak organic acids against uropathogens.

BACKGROUND: 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. AIM: 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). METHODS: 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. FINDINGS: 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. CONCLUSION: The synergistic multi-mechanistic combinations identified herein are anticipated to play an important role in the treatment and prevention of catheter-associated UTIs.

Effect of pH on the in vitro susceptibility of planktonic and biofilm-grown Proteus mirabilis to the quinolone antimicrobials.

AIMS: To examine the effect of elevated pH, as reported during urinary catheter infections, on quinolone activity against the urease-producing pathogen Proteus mirabilis. METHODS AND RESULTS: Susceptibility of Pr. mirabilis to nalidixic acid, norfloxacin and ciprofloxacin was examined in media of pH 5 to pH 10 by determination of MICs, MBCs, minimum biofilm eradication concentrations (MBECs) and time-kill assays. Elevation of media pH from 5 to 9 caused a 10-fold decrease in bacteriostatic activity of nalidixic acid and was also associated with loss of the characteristic 'paradoxical' bactericidal activity. Alkaline pH, however, increased both bacteriostatic and bactericidal activities of the two fluoroquinolones tested against both planktonic and biofilm-associated Pr. mirabilis; MBC and MBEC values for ciprofloxacin decreased approx. 6000-fold and 10-fold, respectively, between pH 5 and pH 9. Rates of kill of all three agents were most rapid at pH 7, the optimal pH for bacterial replication. CONCLUSIONS: pH has a pronounced effect on quinolone-mediated killing, which may be attributed to the dependence of cellular uptake on quinolone ionization state. SIGNIFICANCE AND IMPACT OF THE STUDY: These results provide rationale for the use of these agents for Pr. mirabilis eradication in alkaline environments, including urinary catheter infections: the incidence, recurrence and recalcitrance of which pose a significant burden to healthcare providers.