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Clinical Assistant Professor, College of Pharmacy, University of South Carolina Campus, Columbia, SC
Clinical Coordinator, Infectious Diseases, Department of Pharmacy, Wake Forest University Baptist Medical Center, Winston-Salem, NC
Laboratory Technician, Department of Infectious Diseases, School of Medicine, Wake Forest University
Professor and Chair, Department of Infectious Diseases, Infection Control & Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX
Professor of Medicine and Hospital Epidemiologist, Section on Infectious Diseases, School of Medicine, Wake Forest University
Reprints: Dr. Bookstaver, South Carolina College of Pharmacy, University of South Carolina Campus, 715 Sumter St., CLS-312C, Columbia, SC 29208, fax 803/777-2820, bookstaver{at}sccp.sc.edu
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 log10 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 log10 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.
Key Words: antibiotic lock, catheter-related bloodstream infection, central venous catheter, daptomycin, gentamicin, tigecycline
Published Online, February 3, 2009. www.theannals.com, DOI 10.1345/aph.1L145
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  N. Fernandez-Hidalgo, J. Gavalda, B. Almirante, M.-T. Martin, P. Lopez Onrubia, X. Gomis, and A. Pahissa Evaluation of linezolid, vancomycin, gentamicin and ciprofloxacin in a rabbit model of antibiotic-lock technique for Staphylococcus aureus catheter-related infection J. Antimicrob. Chemother., March 1, 2010; 65(3): 525 - 530. [Abstract] [Full Text] [PDF]
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