Activity of novel antibiotic lock solutions in a model against isolates of catheter-related bloodstream infections.
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.
Bookstaver
P Brandon
PB
College of Pharmacy, University of South Carolina Campus, Columbia, SC 29208, USA. bookstaver@sccp.sc.edu
Williamson
John C
JC
Tucker
Brian Keith
BK
Raad
Issam I
II
Sherertz
Robert J
RJ
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
D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D005839:Gentamicins; D007552:Isotonic Solutions; C010380:Locke's solution; D000078304:Tigecycline; D008911:Minocycline; D017576:Daptomycin