title: Activity of novel antibiotic lock solutions in a model against isolates of catheter-related bloodstream infections.
abstract: 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.
authors.affiliation: College of Pharmacy, University of South Carolina Campus, Columbia, SC 29208, USA. bookstaver@sccp.sc.edu
authors.forename: P Brandon
authors.initials: PB
authors.lastname: Bookstaver
authors.forename: John C
authors.initials: JC
authors.lastname: Williamson
authors.forename: Brian Keith
authors.initials: BK
authors.lastname: Tucker
authors.forename: Issam I
authors.initials: II
authors.lastname: Raad
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Sherertz
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D000925:Anticoagulants / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D055499:Catheter-Related Infections / Q000097:blood* / Q000188:drug therapy*; D002405:Catheterization, Central Venous; D015169:Colony Count, Microbial; D017576:Daptomycin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005839:Gentamicins / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D007552:Isotonic Solutions; D008911:Minocycline / Q000031:analogs & derivatives / Q000627:therapeutic use; D008962:Models, Theoretical; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D005839:Gentamicins; D007552:Isotonic Solutions; C010380:Locke's solution; D000078304:Tigecycline; D008911:Minocycline; D017576:Daptomycin