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. 2022 May 27;12(6):802.
doi: 10.3390/life12060802.

Novel Antimicrobial Strategies to Prevent Biofilm Infections in Catheters after Radical Cystectomy: A Pilot Study

Rosa Gaglione  1   2 , Katia Pane  3 , Maria De Luca  1 , Monica Franzese  3 , Angela Arciello  1   2 , Francesco Trama  4 , Stefano Brancorsini  5 , Marco Salvatore  3 , Ester Illiano  4 , Elisabetta Costantini  4
Affiliations

Novel Antimicrobial Strategies to Prevent Biofilm Infections in Catheters after Radical Cystectomy: A Pilot Study

Rosa Gaglione et al. Life (Basel). .

Abstract

Catheter-associated infections in bladder cancer patients, following radical cystectomy or ureterocutaneostomy, are very frequent, and the development of antibiotic resistance poses great challenges for treating biofilm-based infections. Here, we characterized bacterial communities from catheters of patients who had undergone radical cystectomy for muscle-invasive bladder cancer. We evaluated the efficacy of conventional antibiotics, alone or combined with the human ApoB-derived antimicrobial peptide r(P)ApoBLAla, to treat ureteral catheter-colonizing bacterial communities on clinically isolated bacteria. Microbial communities adhering to indwelling catheters were collected during the patients' regular catheter change schedules (28 days) and extracted within 48 h. Living bacteria were characterized using selective media and biochemical assays. Biofilm growth and novel antimicrobial strategies were analyzed using confocal laser scanning microscopy. Statistical analyses confirmed the relevance of the biofilm reduction induced by conventional antibiotics (fosfomycin, ceftriaxone, ciprofloxacin, gentamicin, and tetracycline) and a well-characterized human antimicrobial peptide r(P)ApoBLAla (1:20 ratio, respectively). Catheters showed polymicrobial communities, with Enterobactericiae and Proteus isolates predominating. In all samples, we recorded a meaningful reduction in biofilms, in both biomass and thickness, upon treatment with the antimicrobial peptide r(P)ApoBLAla in combination with low concentrations of conventional antibiotics. The results suggest that combinations of conventional antibiotics and human antimicrobial peptides might synergistically counteract biofilm growth on ureteral catheters, suggesting novel avenues for preventing catheter-associated infections in patients who have undergone radical cystectomy and ureterocutaneostomy.

Keywords: antibiofilm agents; antimicrobial peptides; antimicrobial resistance; combination therapy; conventional antibiotics; microbial communities; radical cystectomy; urinary catheter-associated infections.

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Conflict of interest statement

The authors declare no conflict of interest. The company had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Analysis of the heterogeneous composition of microbial communities extracted from patients’ ureteral catheters. (A) Pie charts showing the bacterial composition of heterogeneous microbial communities extracted from ureteral catheters for each patient. (B) Identification of isolated bacterial strains according to biochemical tests.
Figure 2
Figure 2
Analysis of the antibiofilm activity of the antimicrobial peptide r(P)ApoBLAla and of the antibiotics fosfomycin or ceftriaxone determined by confocal laser scanning microscopy (CLSM) in static live conditions. Agents were tested alone or in combination. (A) Fluorescence intensities determined by CLSM after 24 h in the absence (control group) or in the presence of r(P)ApoBLAla of the antibiotics fosfomycin or ceftriaxone, or of combinations of the antimicrobial peptide with each antibiotic. Statistical significance codes are shown only for the significant differences in the comparison of interest as * p < 0.05, ** p < 0.01, **** p < 0.0001. (Pairwise Wilcoxon tests, adjusted p-value according to the Benjamini–Hochberg method.) (B) Three-dimensional reconstructions of biofilm images acquired by CLSM for each catheter extract in the absence or in the presence of antibiofilm agents under study.
Figure 3
Figure 3
Analysis of the antibiofilm activity of the antimicrobial peptide r(P)ApoBLAla and the antibiotics ciprofloxacin, gentamicin, or tetracycline by confocal laser scanning microscopy (CLSM) in static live conditions. Agents were tested alone or in combination. (A) Fluorescence mean intensities determined by CLSM upon 24 h in the absence (control group) or in the presence of r(P)ApoBLAla, of the antibiotics ciprofloxacin, gentamicin, or tetracycline, or of combinations of the antimicrobial peptide with each antibiotic. Statistical significance codes are shown only for the significant differences in the comparison of interest as **** p < 0.0001. (Pairwise Wilcoxon tests, adjusted p-value according to the Benjamini–Hochberg method.) (B) Three-dimensional reconstructions of biofilm images acquired by CLSM for each catheter extract in the absence or in the presence of antibiofilm agents under study.
Figure 4
Figure 4
Average biofilm thickness by confocal laser scanning microscopy (CLSM). (A) Thickness of individual-patient-derived catheter extracts U1, U4, and U5 upon incubation with antimicrobial agents r(P)ApoBLAla fosfomycin or ceftriaxone alone or in combination with peptide. (B) Thickness of individual-patient-derived catheter extracts U1, U3, and U5 upon incubation with antimicrobial agents r(P)ApoBLAla or ciprofloxacin, gentamicin, or tetracycline alone or in combination with peptide. One-way ANOVA of the thickness was determined independently. Letter-based plot (a–f letters) for statistical Tukey’s multiple comparison post hoc test significance. Boxes with no letters in common are significantly different (p adjusted < 0.05).
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References

    1. Klein R.D., Hultgren S.J. Urinary tract infections: Microbial pathogenesis, host–pathogen interactions and new treatment strategies. Nat. Rev. Microbiol. 2020;18:211–226. doi: 10.1038/s41579-020-0324-0. - DOI - PMC - PubMed
    1. Sanli O., Dobruch J., Knowles M.A., Burger M., Alemozaffar M., Nielsen M.E., Lotan Y. Bladder cancer. Nat. Rev. Dis. Primers. 2017;3:17022. doi: 10.1038/nrdp.2017.22. - DOI - PubMed
    1. Pane K., Mirabelli P., Coppola L., Illiano E., Salvatore M., Franzese M. New Roadmaps for Non-muscle-invasive Bladder Cancer with Unfavorable Prognosis. Front. Chem. 2020;8:600. doi: 10.3389/fchem.2020.00600. - DOI - PMC - PubMed
    1. Rouprêt M., Babjuk M., Burger M., Capoun O., Cohen D., Compérat E.M., Cowan N.C., Dominguez-Escrig J.L., Gontero P., Hugh Mostafid A., et al. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2020 Update. Eur. Urol. 2020;79:62–79. doi: 10.1016/j.eururo.2020.05.042. - DOI - PubMed
    1. Saint S., Lipsky B.A. Preventing catheter-related bacteriuria: Should we? Can we? How? Arch. Intern. Med. 1999;159:800–808. doi: 10.1001/archinte.159.8.800. - DOI - PubMed

Grants and funding

This work was supported by “Progetti di Ricerca Corrente” funded by the Italian Ministry of Health of IRCCS SYNLAB SDN.

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