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

<div><p>Formation of resilient biofilms on medical devices colonized by pathogenic microorganisms is a major cause of health-care associated infection. While <em>in vitro</em> biofilm analyses led to promising anti-biofilm approaches, little is known about their translation to <em>in vivo</em> situations and on host contribution to the <em>in vivo</em> dynamics of infections on medical devices. Here we have developed an <em>in vivo</em> 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, <em>Escherichia coli</em>, <em>Pseudomonas aeruginosa</em>, <em>Staphylococcus aureus</em> and <em>Staphylococcus epidermidis</em>, 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 <em>in vivo</em> model enables to assess innovative therapeutic strategies against bacterial biofilm infections.</p>