Impregnation of indwelling urinary catheter with promethazine: A strategy to combat catheter-associated urinary tract infections

Abstract

Urinary tract infections (UTIs) associated with indwelling catheters pose a major clinical challenge due to the frequent association with bacterial biofilms, which contribute to antimicrobial resistance and persistent infections. This study aimed to evaluate the antimicrobial and antibiofilm effects of promethazine (PMZ) impregnated in catheter fragments against Gram-negative bacilli associated with UTIs. Twenty-three clinical isolates were tested, including Escherichia coli (n = 5), Klebsiella pneumoniae (n = 6), Proteus mirabilis (n = 6), and Pseudomonas aeruginosa (n = 6). The susceptibility of bacterial isolates to PMZ in planktonic and biofilm growth was assessed. Biofilm biomass reduction was evaluated using PMZ at concentrations corresponding to the minimum inhibitory concentration (MIC), MIC/2, and MIC/4 for growing biofilms, and at the minimum biofilm eradication concentration (MBEC), MBEC/2, and 2 ×MBEC for mature biofilms. Foley catheter fragments were impregnated with PMZ at 390 μg/mL and 3900 μg/mL to assess its effect on biofilm formation by colony-forming unit (CFU) quantification. MICs ranged from 97.6 to 781.25 μg/mL, while MBECs varied from 390.6 to 3125 μg/mL. PMZ significantly reduced the biomass of growing biofilms by 37.3%, 41.5%, and 58.7% at MIC/4, MIC/2, and MIC, respectively (P < 0.05). Catheter impregnation with 390 μg/mL PMZ did not significantly reduce overall CFU counts, but achieved 3-log reductions for E. coli and P. mirabilis. At 3900 μg/mL, PMZ significantly reduced CFU counts for all species, achieving reductions greater than 5-log, when compared to growth control. In addition, PMZ enhanced the antibiofilm activity of conventional antimicrobials. These findings suggest that PMZ is a potential alternative to prevent catheter-associated UTIs caused by Gram-negative bacilli.