Lack of antimicrobial activity of sodium heparin for treating experimental catheter-related infection due to Staphylococcus aureus using the antibiotic-lock technique

Clin Microbiol Infect. 2001 Apr;7(4):206-12. doi: 10.1046/j.1469-0691.2001.00233.x.

Abstract

Objective: To elucidate the potential antimicrobial activity of sodium heparin in the treatment of catheter-infection using the antibiotic-lock technique.

Methods: We performed in vitro studies of the antibiotic susceptibility, stability and synergy of sodium heparin, vancomycin and ciprofloxacin. Efficacy studies were performed in a new animal model of Staphylococcus aureus catheter-related infection in which infection was produced via the endoluminal route. White New Zealand rabbits were surgically implanted with a sylastic catheter into the inferior cava vein. Immediately afterwards, infection was induced by filling and locking the catheters with 0.7 mL of broth culture containing 108 colony-forming units of S. aureus. Eighteen hours later the antibiotic-lock technique was started. Treatment groups were: control without treatment, sodium heparin at 2500 IU/mL, vancomycin at 2500 mg/L, ciprofloxacin at 1000 mg/L, vancomycin plus heparin and ciprofloxacin plus heparin.

Results: Sodium heparin showed an MIC90 higher than 6000 UI/mL against S. aureus causing catheter infection. Studies of antimicrobial synergy by the time-kill method between vancomycin and ciprofloxacin at MIC with sodium heparin at 2500 IU/mL showed no interactions. Vancomycin (2000 microg/mL) and ciprofloxacin (1000 microg/mL) in a solution containing sodium heparin (2500 IU/mL) were stable at 37 degrees C for a 72-h period. Two sets of in vivo experiments were carried out using differents strains of S. aureus. In both cases, sodium heparin showed no therapeutic efficacy when compared to control group and did not increase the antibiotic efficacy when used in combination with vancomycin or ciprofloxacin.

Conclusion: Sodium heparin lacked antibacterial activity against S. aureus causing catheter-related infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Anticoagulants / pharmacology*
  • Anticoagulants / therapeutic use
  • Catheterization / adverse effects*
  • Ciprofloxacin / chemistry
  • Ciprofloxacin / pharmacology
  • Disease Models, Animal
  • Drug Stability
  • Drug Synergism
  • Drug Therapy, Combination
  • Heparin / pharmacology*
  • Heparin / therapeutic use
  • Microbial Sensitivity Tests
  • Rabbits
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / etiology
  • Staphylococcus aureus / drug effects*
  • Treatment Outcome
  • Vancomycin / chemistry
  • Vancomycin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Anticoagulants
  • Ciprofloxacin
  • Vancomycin
  • Heparin