title: Quorum sensing inhibitor FS3-coated vascular graft enhances daptomycin efficacy in a rat model of staphylococcal infection.
abstract: The aim of the study was to investigate the efficacy of the quorum sensing inhibitor FS3 and daptomycin in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2×10(7) colony-forming units of Staphylococcus aureus, strain Smith diffuse. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis and three contaminated groups that received: (i) intraperitoneal daptomycin, (ii) FS3-soacked graft, and (iii) daptomycin plus FS3-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro binding-study was performed to quantify the how much FS3 was coated to the surface of the prosthesis. The in vitro studies showed, that minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values for daptomycin were lower in presence of FS3. In in vivo studies, when tested alone, daptomycin and FS3 showed good efficacies. Their combination showed efficacies significantly higher than that of each single compound. Daptomycin is an important candidate for prevention of staphylococcal biofilm related infection and FS3 could serve as an interesting anti-staphylococcal antibiotic enhancer.
authors.affiliation: Clinic of Infectious Diseases, Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy. o.cirioni@univpm.it
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.forename: Federico
authors.initials: F
authors.lastname: Mocchegiani
authors.forename: Ivana
authors.initials: I
authors.lastname: Cacciatore
authors.forename: Jacopo
authors.initials: J
authors.lastname: Vecchiet
authors.forename: Carmela
authors.initials: C
authors.lastname: Silvestri
authors.forename: Leonardo
authors.initials: L
authors.lastname: Baldassarre
authors.forename: Claudio
authors.initials: C
authors.lastname: Ucciferri
authors.forename: Elena
authors.initials: E
authors.lastname: Orsetti
authors.forename: Pamela
authors.initials: P
authors.lastname: Castelli
authors.forename: Mauro
authors.initials: M
authors.lastname: Provinciali
authors.forename: Marco
authors.initials: M
authors.lastname: Vivarelli
authors.forename: Erika
authors.initials: E
authors.lastname: Fornasari
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
mesh_terms: D000818:Animals; D017576:Daptomycin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D019736:Prostheses and Implants / Q000009:adverse effects / Q000382:microbiology; D053038:Quorum Sensing / Q000187:drug effects*; D051381:Rats; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity; D058017:Vascular Grafting / Q000009:adverse effects
chemical_list: D017576:Daptomycin