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Antifungal activity of a ?-peptide in synthetic urine media: Toward materials-based approaches to reducing catheter-associated urinary tract fungal infections.

ABSTRACT: Catheter-associated urinary tract infections (CAUTI) are the most common type of hospital-acquired infection, with more than 30 million catheters placed annually in the US and a 10-30% incidence of infection. Candida albicans forms fungal biofilms on the surfaces of urinary catheters and is the leading cause of fungal urinary tract infections. As a step toward new strategies that could prevent or reduce the occurrence of C. albicans-based CAUTI, we investigated the ability of antifungal ?-peptide-based mimetics of antimicrobial peptides (AMPs) to kill C. albicans and prevent biofilm formation in synthetic urine. Many ?-peptide-based AMPs exhibit antifungal activities, but are unstable in high ionic strength media and are easily degraded by proteases-features that limit their use in urinary catheter applications. Here, we demonstrate that ?-peptides designed to mimic the amphiphilic helical structures of AMPs retain 100% of their structural stability and exhibit antifungal and anti-biofilm activity against C. albicans in a synthetic medium that mimics the composition of urine. We demonstrate further that these agents can be loaded into and released from polymer-based multilayer coatings applied to polyurethane, polyethylene, and silicone tubing commonly used as urinary catheters. Our results reveal catheters coated with ?-peptide-loaded multilayers to kill planktonic fungal cells for up to 21days of intermittent challenges with C. albicans and prevent biofilm formation on catheter walls for at least 48h. These new materials and approaches could lead to advances that reduce the occurrence of fungal CAUTI.Catheter-associated urinary tract infections are the most common type of hospital-acquired infection. The human pathogen Candida albicans is the leading cause of fungal urinary tract infections, and forms difficult to remove 'biofilms' on the surfaces of urinary catheters. We investigated synthetic ?-peptide mimics of natural antimicrobial peptides as an approach to kill C. albicans and prevent biofilm formation in media that mimics the composition of urine. Our results reveal these mimics to retain structural stability and activity against C. albicans in synthetic urine. We also report polymer-based approaches to the local release of these agents within urinary catheter tubes. With further development, these materials-based approaches could lead to advances that reduce the occurrence of fungal urinary tract infections.

SUBMITTER: Raman N

PROVIDER: S-EPMC5012908 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Antifungal activity of a β-peptide in synthetic urine media: Toward materials-based approaches to reducing catheter-associated urinary tract fungal infections.

Raman Namrata N Lee Myung-Ryul MR Rodríguez López Angélica de L AL Palecek Sean P SP Lynn David M DM

Acta biomaterialia 20160712

<h4>Unlabelled</h4>Catheter-associated urinary tract infections (CAUTI) are the most common type of hospital-acquired infection, with more than 30 million catheters placed annually in the US and a 10-30% incidence of infection. Candida albicans forms fungal biofilms on the surfaces of urinary catheters and is the leading cause of fungal urinary tract infections. As a step toward new strategies that could prevent or reduce the occurrence of C. albicans-based CAUTI, we investigated the ability of ...[more]

PMID: 27422198

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Project description:BackgroundBoth long (> 30 days) and short-term (≤ 30 days) catheterisation has been associated with urinary tract infections (UTIs) due to the invasive nature of device insertion through the urethra. Catheter associated Urinary Tract Infections (CAUTIs) are common (prevalence of ~ 8.5%) infections which can be treated with antibiotics; however, CAUTIs are both expensive to treat and contributes to the antibiotic usage crisis. As catheters are unlikely be replaced for the management of patients' urination, ways of reducing CAUTIs are sought out, using the catheter device itself. The aim of this review is to assess the incidence of CAUTI and the causative micro-organisms when different urinary catheter devices have been used by humans, as reported in published research articles.MethodsA Systematic Literature Review was conducted in Ovid Medline, Web of Science and PubMed, to identify studies which investigated the incidence of UTI and the causative micro-organisms, in patients with different urinary catheter devices. The articles were selected based on a strict set of inclusion and exclusion criteria. The data regarding UTI incidence was extracted and calculated odds ratio were compared across studies and pooled when types of catheters were compared. CAUTI causative micro-organisms, if stated within the research pieces, were also gathered.ResultsA total of 890 articles were identified, but only 26 unique articles met the inclusion/exclusion criteria for this review. Amongst the large cohort there were catheters of materials silicone, latex and PVC and catheter modifications of silver nanoparticles and nitrofurantoin antibiotics. The meta-analysis did not provide a clear choice towards a single catheter against another although silver-based catheters, and silver alloy, appeared to statistically reduce the OR of developing CAUTIs. At genus level the three commonest bacteria identified across the cohort were E. coli, Enterococcus spp. and Pseudomonas spp. whilst considering only at the genus level, with E. coli, Klebsiella pneumonia and Enterococcus faecalis most common at the species-specific level.ConclusionsThere does not appear to be a catheter type, which can significantly reduce the incidence of CAUTI's in patients requiring catheterisation. Ultimately, this warrants further research to identify and develop a catheter device material that will reduce the incidence for CAUTIs.

Project description:Despite advances in infection prevention and control, catheter-associated urinary tract infections (CAUTIs) are common and remain problematic. A number of measures can be taken to reduce the risk of CAUTI in hospitals. Appropriate urinary catheter insertion procedures are one such method. Reducing bacterial colonisation around the meatal or urethral area has the potential to reduce CAUTI risk. However, evidence about the best antiseptic solutions for meatal cleaning is mixed, resulting in conflicting recommendations in guidelines internationally. This paper presents the protocol for a study to evaluate the effectiveness (objective 1) and cost-effectiveness (objective 2) of using chlorhexidine in meatal cleaning prior to catheter insertion, in reducing catheter-associated asymptomatic bacteriuria and CAUTI.A stepped wedge randomised controlled trial will be undertaken in three large Australian hospitals over a 32-week period. The intervention in this study is the use of chlorhexidine (0.1%) solution for meatal cleaning prior to catheter insertion. During the first 8?weeks of the study, no hospital will receive the intervention. After 8?weeks, one hospital will cross over to the intervention with the other two participating hospitals crossing over to the intervention at 8-week intervals respectively based on randomisation. All sites complete the trial at the same time in 2018. The primary outcomes for objective 1 (effectiveness) are the number of cases of CAUTI and catheter-associated asymptomatic bacteriuria per 100 catheter days will be analysed separately using Poisson regression. The primary outcome for objective 2 (cost-effectiveness) is the changes in costs relative to health benefits (incremental cost-effectiveness ratio) from adoption of the intervention.Results will be disseminated via peer-reviewed journals and presentations at relevant conferences.A dissemination plan it being developed. Results will be published in the peer review literature, presented at relevant conferences and communicated via professional networks.Ethics approval has been obtained.12617000373370, approved 13/03/2017. Protocol version 1.1.

Dataset Information

Antifungal activity of a ?-peptide in synthetic urine media: Toward materials-based approaches to reducing catheter-associated urinary tract fungal infections.

Publications

Antifungal activity of a β-peptide in synthetic urine media: Toward materials-based approaches to reducing catheter-associated urinary tract fungal infections.

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