Activity of novel antibiotic lock solutions in a model against isolates of catheter-related bloodstream infections

Ann Pharmacother. 2009 Feb;43(2):210-9. doi: 10.1345/aph.1L145. Epub 2009 Feb 3.


Background: Catheter-related bloodstream infections (CRBSIs) are a primary concern in patients with indwelling central venous catheters (CVCs). Instillation of an antibiotic lock solution may serve as an adjunctive therapy.

Objective: To evaluate the efficacy of novel antibiotic-anticoagulant lock solutions using an in vitro model of CVC infection.

Methods: The following lock solutions were evaluated: daptomycin 1 mg/mL (reconstituted with lactated Ringer's [LR]) plus heparin 5000 units/mL, tigecycline 0.5 mg/mL plus ethylenediaminetetraacetate (EDTA) 30 mg/mL, gentamicin 5 mg/mL plus EDTA 30 mg/mL, cefazolin 5 mg/mL plus heparin 5000 units/mL, and phosphate-buffered NaCl 0.9% as the control solution. Analysis was performed on Hickman catheter segments inoculated with the following organisms: methicillin-sensitive Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, and Pseudomonas aeruginosa. The catheters were incubated in the candidate lock solutions for 0, 2, 4, and 24 hours. Student's t-tests were conducted to evaluate reduction in log(10) colony-forming units/milliliter (cfu/mL) of individual lock solutions compared with the control solution. For each organism, analysis of variance and Student's t-tests were performed to determine whether differences existed among the lock solutions.

Results: Gentamicin plus EDTA (G+EDTA) and tigecycline plus EDTA (Ti+EDTA) resulted in significant reductions (p < 0.05) of log(10) cfu/mL at 24 hours for all organisms tested. Daptomycin, reconstituted in LR, plus heparin (D+LR+H) demonstrated potent activity against all staphylococcal species (p < 0.05). With respect to MRSA, G+EDTA displayed significantly better activity than Ti+EDTA and cefazolin plus heparin (p < 0.05), but there was no significant difference compared with D+LR+H. No antagonism was noted with the addition of anticoagulants to the solutions.

Conclusions: Gentamicin, tigecycline, and daptomycin in combination with anticoagulants as lock solutions displayed potent activity against common pathogens responsible for CRBSIs. Each of these lock solutions deserves strong consideration for study in a clinical trial. Further data on compatibility and stability of these solutions are needed before routine clinical use can be recommended.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Anticoagulants / administration & dosage*
  • Anticoagulants / pharmacology
  • Anticoagulants / therapeutic use
  • Catheter-Related Infections / blood*
  • Catheter-Related Infections / drug therapy*
  • Catheterization, Central Venous
  • Colony Count, Microbial
  • Daptomycin / therapeutic use
  • Drug Therapy, Combination
  • Gentamicins / therapeutic use
  • Humans
  • In Vitro Techniques
  • Isotonic Solutions*
  • Minocycline / analogs & derivatives
  • Minocycline / therapeutic use
  • Models, Theoretical
  • Tigecycline


  • Anti-Bacterial Agents
  • Anticoagulants
  • Gentamicins
  • Isotonic Solutions
  • Locke's solution
  • Tigecycline
  • Minocycline
  • Daptomycin