A Rat Model of Central Venous Catheter to Study Establishment of Long-Term Bacterial Biofilm and Related Acute and Chronic Infections

Abstract

Formation of resilient biofilms on medical devices colonized by pathogenic microorganisms is a major cause of health-care associated infection. While in vitro biofilm analyses led to promising anti-biofilm approaches, little is known about their translation to in vivo situations and on host contribution to the in vivo dynamics of infections on medical devices. Here we have developed an in vivo model of long-term bacterial biofilm infections in a pediatric totally implantable venous access port (TIVAP) surgically placed in adult rats. Using non-invasive and quantitative bioluminescence, we studied TIVAP contamination by clinically relevant pathogens, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidis, and we demonstrated that TIVAP bacterial populations display typical biofilm phenotypes. In our study, we showed that immunocompetent rats were able to control the colonization and clear the bloodstream infection except for up to 30% that suffered systemic infection and death whereas none of the immunosuppressed rats survived the infection. Besides, we mimicked some clinically relevant TIVAP associated complications such as port-pocket infection and hematogenous route of colonization. Finally, by assessing an optimized antibiotic lock therapy, we established that our in vivo model enables to assess innovative therapeutic strategies against bacterial biofilm infections.

Accumulation-Associated Protein Enhances Staphylococcus epidermidis Biofilm Formation under Dynamic Conditions and Is Required for Infection in a Rat Catheter Model

“…In validating our model, we found that rats required immunosuppression and a high inoculum, consistent with previous reports (76,77,88,89). Following validation, we used the model to assess virulence of the mutant S. epidermidis strains 3 days postinfection.…”

“…***, P Ͻ 0.001; **, P Ͻ 0.01; *, P Ͻ 0.05 (n Ն 4 biological replicates). inocula of S. epidermidis from the bloodstream in the absence of a foreign body (76,77), to increase the percentage of catheters seeded following S. epidermidis challenge, rats were given intraperitoneal injections of CP to produce leukopenia. To validate our model and confirm that the presence of a catheter and immunosuppression are critical for S. epidermidis infection, rats were divided into four groups prior to bacterial inoculation: (i) catheter plus CP, (ii) catheter only, (iii) CP only, and (iv) no catheter or CP (no treatment).…”

Biofilm-Related Infections: Bridging the Gap between Clinical Management and Fundamental Aspects of Recalcitrance toward Antibiotics

“…Using a rat model of biofilm-related infection with a totally implantable venous access port (TIVAP), it was recently shown that the gentamicin-EDTA combination was the most effective lock solution compared to gentamicin alone, EDTA alone, or ethanol (70%) (87,344). Gentamicin-EDTA is therefore a potential lock solution able to cure highly tolerant biofilms and eradicate persistent bacteria, thereby preventing recurrence of Gram-positive as well as Gram-negative bacterial biofilms on TIVAP (344).…”

Full and Broad-Spectrum In Vivo Eradication of Catheter-Associated Biofilms Using Gentamicin-EDTA Antibiotic Lock Therapy

“…While some studies showed that combinations of different antibiotics are more efficient than single-antibiotic lock solutions (1,9,34), the efficacy of nonantibiotic compounds is currently being investigated to improve lock solutions and reduce the use of antibiotics.…”