Fibrinogen Release and Deposition on Urinary Catheters Placed during Urological Procedures

Abstract

Purpose: Catheter associated urinary tract infections account for approximately 40% of all hospital acquired infections worldwide with more than 1 million cases diagnosed annually. Recent data from a catheter associated urinary tract infection animal model has shown that inflammation induced by catheterization releases host fibrinogen, which accumulates on the catheter. Further, Enterococcus faecalis catheter colonization was found to depend on EbpA (endocarditis and biofilm-associated pilus), a fibrinogen binding adhesin. We evaluated this mechanism in a human model.

Materials and methods: Urinary catheters were collected from patients hospitalized for surgical or nonsurgical urological procedures. Catheters were subjected to immunofluorescence analyses by incubation with antifibrinogen antibody and then staining for fluorescence. Fluorescence intensity was compared to that of standard catheters. Catheters were incubated with strains of Enterococcus faecalis, Staphylococcus aureus or Candida to assess binding of those strains to fibrinogen laden catheters.

Results: After various surgical and urological procedures, 50 catheters were collected. In vivo dwell time ranged from 1 hour to 59 days. All catheters had fibrinogen deposition. Accumulation depended on dwell time but not on surgical procedure or catheter material. Catheters were probed ex vivo with E. faecalis, S. aureus and Candida albicans, which bound to catheters only in regions where fibrinogen was deposited.

Conclusions: Taken together, these data show that urinary catheters act as a binding surface for the accumulation of fibrinogen. Fibrinogen is released due to inflammation resulting from a urological procedure or catheter placement, creating a niche that can be exploited by uropathogens to cause catheter associated urinary tract infections.

Keywords: catheterization; fibrinogen; hospitalization; iatrogenic disease; urinary tract infections.

Figure 1. Representative images of the different urinary catheter materials and visualization of their fibrinogen deposition

A) 100 % silicone; B) silicon elastomer; and C) latex. The first 10 cm of the catheter tip was used for fibrinogen deposition analysis. Deposited fibrinogen on the catheter was detected by immunofluorescence using goat anti-human fibrinogen antibody staining.

Figure 2. Correlation between the fibrinogen deposition on urinary catheters and their dwell time

(A) All fifty patient urinary catheters placed as a standard of care were recovered and fixed with formalin. The tip section (10 cm) of each catheter was subjected to analysis by immunofluorescence using antibody staining to detect deposited fibrinogen. (B) Close up view of the catheters with dwell time up to 50 hrs. Quantification of fibrinogen deposition was calculated by standard curves based on each catheter material. The color represents the surgical procedure that the patient underwent and squares denote those patients that had a preoperative positive urine culture. Pearson’ correlation statistical analysis was performed to measure the correlation between fibrinogen deposition and dwell time.

Figure 3. Ex-vivo binding of uropathogens encoding fibrinogen-binding proteins to fibrinogen deposited on human urinary catheters

Urinary catheters from patients with preoperative negative urine culture were used to test the binding of A) E. faecalis, B) S. aureus, and C) C. albicans to fibrinogen deposited onto the catheter. Catheters were incubated with 2 × 10⁷ CFU of the corresponding strain for 1 hour. Detection of the presence and distribution of bacteria and Fg was assessed by immunofluorescent staining. A non-infected catheter was used for each strain for comparison. Catheters incubated only with the secondary antibodies were used as a negative control to assess auto-fluorescence background of the catheter material. Moreover for the E. faecalis binding experiment (A), we used the E. faecalis wild type (OG1RF) and a known fibrinogen deficient mutant (AWAGA) for comparison.