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Natural Cyanobacterial Polymer-Based Coating as a Preventive Strategy to Avoid Catheter-Associated Urinary Tract Infections.

ABSTRACT: Catheter-associated urinary tract infections (CAUTIs) represent about 40% of all healthcare-associated infections. Herein, the authors report the further development of an infection preventive anti-adhesive coating (CyanoCoating) meant for urinary catheters, and based on a natural polymer released by a marine cyanobacterium. CyanoCoating performance was assessed against relevant CAUTI etiological agents, namely Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, methicillin resistant Staphylococcus aureus (MRSA), and Candida albicans in the presence of culture medium or artificial urine, and under biofilm promoting settings. CyanoCoating displayed a broad anti-adhesive efficiency against all the uropathogens tested (68-95%), even in the presence of artificial urine (58-100%) with exception of P. mirabilis in the latter condition. Under biofilm-promoting settings, CyanoCoating reduced biofilm formation by E. coli, P. mirabilis, and C. albicans (30-60%). In addition, CyanoCoating prevented large crystals encrustation, and its sterilization with ethylene oxide did not impact the coating stability. Therefore, CyanoCoating constitutes a step forward for the implementation of antibiotic-free alternative strategies to fight CAUTIs.

SUBMITTER: Costa B

PROVIDER: S-EPMC7344411 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Natural Cyanobacterial Polymer-Based Coating as a Preventive Strategy to Avoid Catheter-Associated Urinary Tract Infections.

Costa Bruna B Mota Rita R Tamagnini Paula P Martins M Cristina L MCL Costa Fabíola F

Marine drugs 20200526 6

Catheter-associated urinary tract infections (CAUTIs) represent about 40% of all healthcare-associated infections. Herein, the authors report the further development of an infection preventive anti-adhesive coating (CyanoCoating) meant for urinary catheters, and based on a natural polymer released by a marine cyanobacterium. CyanoCoating performance was assessed against relevant CAUTI etiological agents, namely Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, methicillin resistant Sta ...[more]

PMID: 32466349

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Project description:Background and objectiveCatheter-associated urinary tract infections (CAUTIs) represent a significant burden in health care and its management is challenging. This study aims to assess and compare central European CAUTIs regarding diagnostics, treatment, and prophylaxis.MethodsAn anonymized online questionnaire was distributed among urologists in Austria, France, Germany, and Switzerland between January and October 2023, consisting of demographic questions on catheter management and diagnostics, treatment, and prophylaxis of CAUTIs. An analysis was performed per country. Comparisons were done with the Fisher's exact test (statistical significance with p < 0.05).Key findings and limitationsOut of 423 participating urologists, most regularly performed catheter changes and managed catheter-related issues, except for French urologists. Swiss urologists tended to change the catheter after a longer interval. In France, a higher estimated number of CAUTIs were observed. Diagnostic symptoms and measures varied significantly between countries. French urologists prescribed more antimicrobials per patient and administered longer treatment regimens. The choice of antimicrobial agents differed notably for nonfebrile and febrile CAUTIs, with cotrimoxazole/nitrofurantoin being common for nonfebrile cases and cephalosporin/amoxicillin for febrile ones. Follow-up protocols were similar among urologists, while prophylactic measures showed variations.Conclusions and clinical implicationsCAUTI management varied notably across countries in terms of diagnostics, treatment, and prophylaxis. Discrepancies in antimicrobial therapy could be influenced by local resistance rates; yet, nonrecommended drugs and prolonged regimens, as compared with guideline recommendations, were common. This trend, along with inappropriate diagnostics and prophylaxis, may increase antimicrobial resistance and CAUTI morbidity. This study emphasizes the necessity for diagnostic and antimicrobial stewardship interventions, and proper training in CAUTI management.Patient summaryIn this questionnaire-based study examining the clinical practices for managing urinary tract infections in patients with bladder catheters (CAUTIs), significant disparities were observed among European urologists regarding diagnosis, treatment, and prophylaxis. These findings underscore the critical need for clear guidelines and comprehensive training in CAUTI management.

Project description:Gram-positive bacteria in the genus Enterococcus are a frequent cause of catheter-associated urinary tract infection (CAUTI), a disease whose treatment is increasingly challenged by multiantibiotic-resistant strains. We have recently shown that E. faecalis uses the Ebp pilus, a heteropolymeric surface fiber, to bind the host protein fibrinogen as a critical step in CAUTI pathogenesis. Fibrinogen is deposited on catheters due to catheter-induced inflammation and is recognized by the N-terminal domain of EbpA (EbpANTD), the Ebp pilus's adhesin. In a murine model, vaccination with EbpANTD confers significant protection against CAUTI. Here, we explored the mechanism of protection using passive transfer of immune sera to show that antisera blocking EbpANTD-fibrinogen interactions not only is prophylactic but also can act therapeutically to reduce bacterial titers of an existing infection. Analysis of 55 clinical CAUTI, bloodstream, and gastrointestinal isolates, including E. faecalis, E. faecium, and vancomycin-resistant enterococci (VRE), revealed a diversity of levels of EbpA expression and fibrinogen-binding efficiency in vitro Strikingly, analysis of 10 strains representative of fibrinogen-binding diversity demonstrated that, irrespective of EbpA levels, EbpANTD antibodies were universally protective. The results indicate that, despite diversity in levels of fibrinogen binding, strategies that target the disruption of EbpANTD-fibrinogen interactions have considerable promise for treatment of CAUTI. Urinary catheterization is a routine medical procedure, and it has been estimated that 30 million Foley catheters are used annually in the United States. Importantly, placement of a urinary catheter renders the patient susceptible to developing a catheter-associated urinary tract infection, accounting for 1 million cases per year. Additionally, these infections can lead to serious complications, including bloodstream infection and death. Enterococcus strains are a common cause of these infections, and management of enterococcal infections has been more difficult in recent years due to the development of antibiotic resistance and the ability of strains to disseminate, resulting in a major threat in hospital settings. In this study, we developed an antibiotic-sparing treatment that is effective against diverse enterococcal isolates, including vancomycin-resistant enterococci, during catheter-associated urinary tract infections.

Project description:Proteus mirabilis is a key pathobiont in catheter-associated urinary tract infections (CA-UTIs), which is well known to form crystalline biofilms that occlude catheters. Urease activity alkylates urine through the release of ammonia, consequentially resulting in higher levels of Mg2+ and Ca2+ and formation of crystals. In this study, we showed that N-acetyl cysteine (NAC), a thiol antioxidant, is a potent urease inhibitor that prevents crystalline biofilm formation. To quantify urease activity, Berthelot's method was done on bacterial extracts treated with NAC. We also used an in vitro catheterised glass bladder model to study the effect of NAC treatment on catheter occlusion and biofilm encrustation in P. mirabilis infections. Inductively-coupled plasma mass spectrometry (ICP-MS) was performed on catheter samples to decipher elemental profiles. NAC inhibits urease activity of clinical P. mirabilis isolates at concentrations as low as 1 mM, independent of bacterial killing. The study also showed that NAC is bacteriostatic on P. mirabilis, and inhibited biofilm formation and catheter occlusion in an in vitro. A significant 4-8log10 reduction in viable bacteria was observed in catheters infected in this model. Additionally, biofilms in NAC treated catheters displayed a depletion of calcium, magnesium, or phosphates (>10 fold reduction), thus confirming the absence of any urease activity in the presence of NAC. Interestingly, we also showed that not only is NAC anti-inflammatory in bladder epithelial cells (BECs), but that it mutes its inflammatory response to urease and P. mirabilis infection by reducing the production of IL-6, IL-8 and IL-1b. Using biochemical, microbiological and immunological techniques, this study displays the functionality of NAC in preventing catheter occlusion by inhibiting urease activity. The study also highlights NAC as a strong anti-inflammatory antibiofilm agent that can target both bacterial and host factors in the treatment of CA-UTIs.

Dataset Information

Natural Cyanobacterial Polymer-Based Coating as a Preventive Strategy to Avoid Catheter-Associated Urinary Tract Infections.

Publications

Natural Cyanobacterial Polymer-Based Coating as a Preventive Strategy to Avoid Catheter-Associated Urinary Tract Infections.

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