RNAIII-inhibiting peptide improves efficacy of clinically used antibiotics in a murine model of staphylococcal sepsis.
RNAIII-inhibiting peptide (RIP, YSPWTNF-NH2) is a quorum-sensing peptide inhibitor that prevents Staphylococcus aureus toxin production and biofilm formation. A mouse sepsis model was used to test the efficacy of RIP alone or in combination with conventional antibiotics in suppressing S. aureus-induced sepsis. Mice were injected intravenously with 3.0x10(6)CFU of S. aureus ATCC 25923 or with 3.0x10(6)CFU of S. aureus strain Smith diffuse. All animals were randomized to receive intravenously isotonic sodium chloride solution as a control, or 20 mg/kg RIP alone or combined with 20 mg/kg cefazolin, 10 mg/kg imipenem, or 10 mg/kg vancomycin immediately or 6 h after bacterial challenge. Main outcome measures were bacteremia and lethality. All compounds reduced lethality when compared to controls. Although, in general combined-treated groups had significant lower bacterial counts when associated to singly-treated groups only the combination between RIP and vancomycin with respect to cefazolin gave a statistically significant decrease in the lethality rate. Lowest lethality rates (10%) and bacteremia (<10(2)CFU/ml) were obtained when RIP was administered in combination with vancomycin. Because RIP can be synergistic with current antibiotic therapies and help to reduce S. aureus exotoxins production, it can be considered a promising agent to associate with antibiotics for further clinical research into treatment of sepsis.
Giacometti
Andrea
A
Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
Cirioni
Oscar
O
Ghiselli
Roberto
R
Dell'Acqua
Giorgio
G
Orlando
Fiorenza
F
D'Amato
Giuseppina
G
Mocchegiani
Federico
F
Silvestri
Carmela
C
Del Prete
Maria Simona
MS
Rocchi
Marco
M
Balaban
Naomi
N
Saba
Vittorio
V
Scalise
Giorgio
G
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D016470:Bacteremia; D002437:Cefazolin / Q000494:pharmacology / Q000627:therapeutic use; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004357:Drug Synergism; D015378:Imipenem / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D011897:Random Allocation; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000401:mortality; D013211:Staphylococcus aureus / Q000187:drug effects; D013997:Time Factors; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D014640:Vancomycin; D015378:Imipenem; D002437:Cefazolin