Dataset Information

Antibody-Based Therapy for Enterococcal Catheter-Associated Urinary Tract Infections.

ABSTRACT: 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 (EbpA^NTD), the Ebp pilus's adhesin. In a murine model, vaccination with EbpA^NTD confers significant protection against CAUTI. Here, we explored the mechanism of protection using passive transfer of immune sera to show that antisera blocking EbpA^NTD-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, EbpA^NTD antibodies were universally protective. The results indicate that, despite diversity in levels of fibrinogen binding, strategies that target the disruption of EbpA^NTD-fibrinogen interactions have considerable promise for treatment of CAUTI.

Importance

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.

SUBMITTER: Flores-Mireles AL

PROVIDER: S-EPMC5080383 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Antibody-Based Therapy for Enterococcal Catheter-Associated Urinary Tract Infections.

Flores-Mireles Ana L AL Walker Jennifer N JN Potretzke Aaron A Schreiber Henry L HL Pinkner Jerome S JS Bauman Tyler M TM Park Alyssa M AM Desai Alana A Hultgren Scott J SJ Caparon Michael G MG

mBio 20161025 5

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 do ...[more]

PMID: 27795399

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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.

Dataset Information

Antibody-Based Therapy for Enterococcal Catheter-Associated Urinary Tract Infections.

Importance

Publications

Antibody-Based Therapy for Enterococcal Catheter-Associated Urinary Tract Infections.

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