Stability and in vitro efficacy of antibiotic-heparin lock solutions potentially useful for treatment of central venous catheter-related sepsis

J Antimicrob Chemother. 2003 Apr;51(4):849-55. doi: 10.1093/jac/dkg179. Epub 2003 Mar 13.

Abstract

Objectives: Increasing numbers of patients for whom infection is a major risk are dependent on central venous catheters. Antibiotic-anticoagulant locks may have a role in preventing or treating catheter-related infections. The aim of this study was to determine the in vitro stability and efficacy of antibiotic-heparin lock solutions.

Methods: Candidate antibiotics (amikacin, ciprofloxacin, flucloxacillin, gentamicin, linezolid, teicoplanin) were investigated in vitro, either individually or in combination, in solution with heparin. The solutions were initially tested for visual precipitation. The efficacy of stable solutions and taurolidine was then tested in a catheter model bioassay system against microorganisms commonly encountered in catheter-related septicaemia.

Results: In general, lower concentrations of heparin (</=1000 U/mL) combined with antibiotics resulted in precipitation, whereas high concentrations (3500-10,000 U/mL) were compatible with a broader range of antibiotic concentrations. The stability of each antibiotic-heparin combination required individual assessment. Bioassays identified the following promising antibiotic-anticoagulant solutions: for broad-spectrum empirical cover, a teicoplanin-ciprofloxacin-heparin solution; for directed use, flucloxacillin-heparin for methicillin-susceptible Staphylococcus aureus (MSSA), high dose teicoplanin-heparin for methicillin-resistant S. aureus (MRSA), high-dose linezolid-heparin for vancomycin-resistant enterococci (VRE) and ciprofloxacin-heparin for (susceptible) Pseudomonas aeruginosa; for prophylactic use, taurolidine.

Conclusion: These solutions now warrant clinical trials to investigate their role in the management of catheter-related septicaemia.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / analysis
  • Anti-Bacterial Agents / therapeutic use*
  • Catheterization, Central Venous / adverse effects*
  • Catheterization, Central Venous / instrumentation
  • Cross Infection / prevention & control*
  • Drug Stability
  • Drug Therapy, Combination / administration & dosage
  • Drug Therapy, Combination / analysis
  • Drug Therapy, Combination / therapeutic use
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Heparin / administration & dosage*
  • Heparin / analysis
  • Heparin / therapeutic use*
  • Microbial Sensitivity Tests

Substances

  • Anti-Bacterial Agents
  • Heparin