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.
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.


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 2x10(7) 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.
Cirioni
Oscar
O
Institute of Infectious Diseases and Public Health, University of Ancona, Ancona, Italy.
Giacometti
Andrea
A
Ghiselli
Roberto
R
Dell'Acqua
Giorgio
G
Gov
Yael
Y
Kamysz
Wojciech
W
Lukasiak
Jerzy
J
Mocchegiani
Federico
F
Orlando
Fiorenza
F
D'Amato
Giuseppina
G
Balaban
Naomi
N
Saba
Vittorio
V
Scalise
Giorgio
G
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination / Q000008:administration & dosage; D006020:Glycopeptides / Q000494:pharmacology; D020007:Implants, Experimental / Q000009:adverse effects* / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D011093:Polyethylene Terephthalates / Q000737:chemistry; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000494:pharmacology; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000472:pathogenicity; D040521:Subcutaneous Tissue / Q000382:microbiology / Q000473:pathology*; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology; D020713:Vancomycin Resistance
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D006020:Glycopeptides; D009842:Oligopeptides; D011093:Polyethylene Terephthalates; D011506:Proteins; C111711:RNAIII inhibiting peptide; C104501:temporin; D014640:Vancomycin; D012293:Rifampin