# A New Bromelain-Based Polyenzymatic Complex Plus N-Acetylcysteine: A Promising Approach for the Treatment of Urinary Tract Infections

## TL;DR

A new formulation combining bromelain and N-acetylcysteine enhances ciprofloxacin's ability to treat urinary tract infections by disrupting bacterial biofilms.

## Contribution

The study introduces a polyenzymatic formulation that enhances antibiotic efficacy against E. coli biofilms in UTIs.

## Key findings

- The formulation increased microbial reduction in mature E. coli biofilms at lower ciprofloxacin concentrations.
- The combination disrupted biofilm structure and increased biomass reduction.
- The formulation improved ciprofloxacin's antimicrobial effect in a Galleria mellonella infection model.

## Abstract

Biofilm plays a crucial role in the pathogenesis and chronicity of urinary tract infections (UTIs). The present work aimed to evaluate the anti-biofilm effects of Formulation (DIF17BRO® plus NAC) in combination with ciprofloxacin (CPX) on Escherichia coli strains. The antimicrobial activity of ciprofloxacin was evaluated by minimum inhibitory concentration (MIC) determination, and the antibiofilm effects of ciprofloxacin alone and combined with Formulation were evaluated on E. coli ATCC700926, E. coli ATCC10536, E. coli PNT, and E. coli PCA mature biofilms in terms of CFU/mL and biomass quantifications. Moreover, the potential protective effects of Formulation plus ciprofloxacin was tested in a Galleria mellonella in vivo infection assay. Our results underlined the increased microbial reduction in the mature biofilm in the presence of the combination Formulation and CPX, even at a lower concentration of CPX. Formulation increased the percentage of biofilm biomass reduction, inducing a disruption of the biofilm structure itself. Our present findings confirm that MIC CPX combined with Formulation also induced an antimicrobial effect in the G. mellonella assay. Formulation facilitated the perturbation of the biofilm polymeric matrix, enhancing the antibiotic penetration and its antimicrobial action on bacteria, underlining Formulation’s role as an enhancer of ciprofloxacin antibacterial action.