Dataset Information

Prevention of urinary catheter-associated infections by coating antimicrobial peptides from crowberry endophytes.

ABSTRACT: Urinary catheters are extensively used in hospitals, being responsible for about 75% of hospital-acquired infections. In this work, a de novo designed antimicrobial peptide (AMP) Chain201D was studied in the context of urinary catheter-associated infections. Chain201D showed excellent antimicrobial activity against relevant ATCC strains and clinical isolates of bacteria and yeast and demonstrated high stability in a wide range of temperatures, pH and salt concentrations. Moreover, the bactericidal activity of Chain201D immobilized on a model surface was studied against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), some of the most prevalent strains found in urinary catheter-associated infections. Chain201D was successfully tethered to ((1-mercapto-11-undecyl)-(tetra(ethylene glycol) (EG4)) terminated self-assembled monolayers (SAMs), (EG4-SAMs), activated by 1,1'-Carbonyldiimidazole (CDI) at different concentrations. Chain201D surfaces can bind and kill by contact a high percentage of adherent bacteria. These achievements are obtained without any peptide modification (for chemoselective conjugation) and without the use of a spacer. Moreover, increased amounts of immobilized AMP lead to higher numbers of adhered/dead bacteria, revealing a concentration-dependent behaviour and demonstrating that Chain201D has excellent potential for developing antimicrobial urinary catheters.

SUBMITTER: Monteiro C

PROVIDER: S-EPMC6656713 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Prevention of urinary catheter-associated infections by coating antimicrobial peptides from crowberry endophytes.

Monteiro Claudia C Costa Fabíola F Pirttilä Anna Maria AM Tejesvi Mysore V MV Martins M Cristina L MCL

Scientific reports 20190724 1

Urinary catheters are extensively used in hospitals, being responsible for about 75% of hospital-acquired infections. In this work, a de novo designed antimicrobial peptide (AMP) Chain201D was studied in the context of urinary catheter-associated infections. Chain201D showed excellent antimicrobial activity against relevant ATCC strains and clinical isolates of bacteria and yeast and demonstrated high stability in a wide range of temperatures, pH and salt concentrations. Moreover, the bactericid ...[more]

PMID: 31341199

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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.

Dataset Information

Prevention of urinary catheter-associated infections by coating antimicrobial peptides from crowberry endophytes.

Publications

Prevention of urinary catheter-associated infections by coating antimicrobial peptides from crowberry endophytes.

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