RNAIII-inhibiting Peptide Significantly Reduces Bacterial Load and Enhances the Effect of Antibiotics in the Treatment of Central Venous Catheter-Associated Staphylococcus Aureus Infections

J Infect Dis. 2006 Jan 15;193(2):180-6. doi: 10.1086/498914. Epub 2005 Dec 9.

Abstract

Background: Medical devices used in clinical practice are often associated with biofilm-associated staphylococcal infections.

Methods: An in vitro antibiotic susceptibility assay of Staphylococcus aureus biofilms using 96-well polystyrene tissue-culture plates was performed to test the effects of RNAIII-inhibiting peptide (RIP), ciprofloxacin, imipenem, and vancomycin. Efficacy studies were performed using a rat model of central venous catheter (CVC)-associated infection. Twenty-four hours after implantation, the catheters were filled with RIP (1 mg/mL). Thirty minutes later, rats were challenged, via the CVC, with 1.0 x 10(6) cfu of S. aureus strain Smith diffuse. The antibiotic-lock technique was begun 24 h later.

Results: Minimum inhibitory concentrations of antibiotics in biofilms were at least 4-fold higher than those against the freely growing planktonic cells. When they were first treated with RIP, the cells in biofilms became as susceptible to antibiotics as did planktonic cells. These data were confirmed by the in vivo studies. In particular, when CVCs were treated with both RIP and antibiotics, the biofilm bacterial load was further reduced to 1 x 10(1) cfu/mL, and bacteremia was not detected, suggesting that there was 100% elimination of bacteremia and a 6 log10 reduction in biofilm bacterial load.

Conclusion: RIP significantly reduces bacterial load and enhances the effect of antibiotics in the treatment of CVC-associated S. aureus infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacteremia / prevention & control
  • Biofilms / drug effects
  • Catheterization, Central Venous / adverse effects*
  • Catheters, Indwelling / microbiology*
  • Ciprofloxacin / pharmacology
  • Ciprofloxacin / therapeutic use
  • Drug Therapy, Combination
  • Imipenem / pharmacology
  • Imipenem / therapeutic use
  • Male
  • Microbial Sensitivity Tests
  • Oligopeptides / pharmacology*
  • Oligopeptides / therapeutic use
  • Rats
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus aureus / drug effects*
  • Vancomycin / pharmacology
  • Vancomycin / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Oligopeptides
  • RNAIII inhibiting peptide
  • Ciprofloxacin
  • Vancomycin
  • Imipenem