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(Circulation. 2003;108:767.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Prophylactic Efficacy of Topical Temporin A and RNAIII-Inhibiting Peptide in a Subcutaneous Rat Pouch Model of Graft Infection Attributable to Staphylococci With Intermediate Resistance to Glycopeptides

Oscar Cirioni, MD; Andrea Giacometti, PhD; Roberto Ghiselli, PhD; Giorgio Dell’Acqua, PhD; Yael Gov, PhD; Wojciech Kamysz, PhD; Jerzy ukasiak, PhD; Federico Mocchegiani, MD; Fiorenza Orlando, PhD; Giuseppina D’Amato, MD; Naomi Balaban, PhD; Vittorio Saba, PhD; Giorgio Scalise, PhD

From the Institute of Infectious Diseases and Public Health (O.C., A.G., G.D., G.S.), Department of General Surgery (R.G., F.M., V.S.), and Biotechnology Centre, Research Department (F.O.), University of Ancona, Italy; Arval Biological Laboratories (G.D.A.), Conthey, Switzerland; Department of Human Microbiology (Y.G., N.B.), Sackler School of Medicine, Tel Aviv University, Israel; and Faculty of Pharmacy (W.K., J.L.), Medical University of Gdask, Poland.

Correspondence to Andrea Giacometti, MD, Clinica delle Malattie Infettive, c/o Ospedale Regionale, Via Conca, 60200 Torrette di Ancona, Italy. E-mail anconacmi{at}interfree.it

Received September 13, 2002; de novo received January 29, 2003; revision received April 24, 2003; accepted April 25, 2003.

Background— Bacteria that adhere to implanted medical devices play an important role in industry and in modern medicine. Staphylococci are among the most common pathogens that cause biomaterial infections. Vascular prosthetic graft infection is one of the most feared complications that the vascular surgeon treats, frequently resulting in prolonged hospitalization, organ failure, amputation, and death. A rat model was used to investigate the topical efficacies of temporin A and the quorum-sensing inhibitor RNAIII-inhibiting protein (RIP) as prophylactic agents of vascular prosthetic graft infections caused by Staphylococcus aureus and Staphylococcus epidermidis with intermediate resistance to glycopeptides.

Methods and Results— Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses 1 cm² followed by topical inoculation with 2x10⁷ colony-forming units of bacterial strains. The study included, for each staphylococcal strain, a control group (no graft contamination), a contaminated group that did not receive antibiotic prophylaxis, and 6 contaminated groups that received grafts soaked with temporin A, RIP, rifampin, temporin A plus RIP, RIP plus rifampin, or temporin A plus RIP. The infection was evaluated by quantitative agar culture. When tested alone, temporin A and RIP showed comparable efficacies, and their efficacies were significantly higher than that of rifampin against both strains. All combinations showed efficacies significantly higher than that of each single compound. The combinations of temporin A and RIP exerted the strongest antistaphylococcal efficacies, eliminating infection by 100%.

Conclusions— The results of the present study make these molecules potentially useful for antimicrobial chemoprophylaxis in vascular surgery.

Key Words: vasculature • grafting • infection • peptides

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