Assessment of Enterococcus faecalis biofilm response to amoxicillin and ciprofloxacin using a dynamic in vitro pharmacokinetic-pharmacodynamic model of catheter-associated urinary tract infection.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are among the most common types of healthcare-associated infections. Among uropathogens, Enterococcus faecalis is particularly notable for its strong capacity to form biofilms on urinary catheters, thereby decreasing its susceptibility to antibiotics commonly used to treat CAUTIs. However, current antibiotic dosing strategies still rely on planktonic phenotypes, limiting their applicability to biofilm-associated infections. To address this limitation, a dynamic in vitro pharmacokinetic-pharmacodynamic model was developed to assess E. faecalis biofilms' response to different treatment regimens. METHODS: Biofilms of model E. faecalis strains (ATCC 29212 and 54) were preformed on urinary catheters. Mature biofilms were subjected to simulated urinary dosing regimens of amoxicillin (500 mg q12h for 3 days) or ciprofloxacin (500 mg q24h for 3 days), as well as to constant antibiotic concentrations for 3 days. Viable bacterial counts and biofilm biomass were then measured at predefined timepoints, and the effects of the simulated dosing regimens were compared to those observed under constant antibiotic exposure. RESULTS: Our findings indicate that daily ciprofloxacin demonstrated the greatest antibacterial activity, significantly surpassing the effects of constant ciprofloxacin exposure, twice-daily dosing of amoxicillin, and constant amoxicillin exposure. Although the simulated amoxicillin regimen was more effective than constant amoxicillin exposure, both achieved only moderate reductions. Notably, constant amoxicillin exposure induced biofilm formation. Ciprofloxacin exhibited markedly greater antibiofilm activity than amoxicillin against both E. faecalis strains. Among the evaluated regimens, CIP 500 mg q24h produced the most pronounced reduction in biofilm bacterial burden, achieving decreases exceeding 3 log10 cfu/cm2 in both strains after 72 h of exposure. CONCLUSIONS: The findings show that antibiotic efficacy against E. faecalis biofilms depends on the antibiotic and its dosing regimen, with fluctuating ciprofloxacin exposure producing the strongest bactericidal effect and biofilm reduction.