The lipopeptides Pal-Lys-Lys-NH(2) and Pal-Lys-Lys soaking alone and in combination with intraperitoneal vancomycin prevent vascular graft biofilm in a subcutaneous rat pouch model of staphylococcal infection.
Staphylococcal infections are often associated with the use of implantable medical devices. Such infections are difficult to treat because of biofilm resistance to antibiotics and are common causes of morbidity and mortality. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2x10(7) colony-forming units of bacterial strains. The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis and five contaminated groups that received intraperitoneal vancomycin, Pal-Lys-Lys-NH(2) and Pal-Lys-Lys-soacked graft, and vancomycin plus Pal-Lys-Lys-NH(2) or Pal-Lys-Lys-soacked graft, respectively. The infection was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro antibiotic susceptibility assay for Staphylococcus aureus biofilms was performed to elucidate the same activity. When tested alone, vancomycin and lipopeptides showed comparable efficacies. All combinations showed efficacies significantly higher than that of each single compound. Vancomycin combined to Pal-Lys-Lys-NH(2) exerted the strongest anti-staphylococcal efficacies. The in vitro studies showed, that MIC and MBC values for vancomycin were lower in presence of lipopeptides. They reduce the bacterial load and to enhance the effect of vancomycin in the prevention of vascular graft staphylococcal infections.
Cirioni
Oscar
O
Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
Giacometti
Andrea
A
Ghiselli
Roberto
R
Kamysz
Wojciech
W
Silvestri
Carmela
C
Orlando
Fiorenza
F
Mocchegiani
Federico
F
Vittoria
Agnese Della
AD
Kamysz
Elzbieta
E
Saba
Vittorio
V
Scalise
Giorgio
G
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D020007:Implants, Experimental / Q000009:adverse effects* / Q000382:microbiology; D007274:Injections, Intraperitoneal; D008297:Male; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D016459:Prosthesis-Related Infections / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D040521:Subcutaneous Tissue / Q000382:microbiology / Q000473:pathology*; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D014640:Vancomycin