Compatibility and Stability of Daptomycin Lock Solutions in Combination with Gentamicin, Azithromycin, Heparin and Trisodium Citrate

Abstract

Background: Antibiotic lock therapy is an interventional modality used for treatment and prevention of central-line associated bloodstream infections. Stability and compatibility data for combinations are lacking, limiting clinical use. Objective: Compatibility and stability of daptomycin lock solutions in combination with azithromycin, gentamicin, and heparin or sodium citrate were evaluated up to 96 hours. Methods: Eight candidate lock solutions were prepared for compatibility and stability testing. All solutions were prepared in glass vials, and included daptomycin 1mg/mL in varying combinations with heparin 100 – 1,000 units/mL, trisodium citrate, azithromycin and/or gentamicin. Lactated Ringer’s solution was added as a diluent in a sufficient quantity to bring the total volume up to 5mL. Drug stability in the admixture was determined by the degradation of the components. The quantification of drugs was performed using Waters Alliance HPLC using Phenomenex Luna C8 (2), 150*2.6mm, 5µ column. A gradient run was executed for 20 minutes with 0.45% ammonium dihydrogen phosphate, pH 3.25 as eluent A and acetonitrile as eluent B at a flow rate of 1.0mL/min. Each solution was visually inspected for particulates and color change. Lock solutions were tested in triplicate. Results: Daptomycin degradation was <10% for all solutions at 48 hours, and for 7 of the 8 solutions at 72 hours. Gentamicin degradation was <5% for solutions in combination with daptomycin and trisodium citrate. No physical incompatibilities were detected. Conclusion: Study data support the stability and compatibility of daptomycin with additives in solution, allowing for fewer exchanges and longer dwell times for a lock solution. The addition of azithromycin or gentamicin may offer synergy and/or extended spectrum of activity. Daptomycin bioactivity with trisodium citrate needs confirmation.

Vancomycin and daptomycin stability in heparin or sodium citrate lock solutions

“…Both antibiotics have been used in combination with sodium citrate with less frequency, so its activity and stability have less evidence. 7,11 Although the use of ALT including heparin as anticoagulant is more common, sodium citrate 4% has gained favorability as a viable option to its safety profile, 1 it has also demonstrated greater activity than heparin in reducing the formation of biofilm according to Jiménez-Hernández et al 12 In addition, there is no substantial difference between heparin lock solutions versus all other types of catheter lock solutions for catheter dysfunction. 13 Most formulations prepared in Hospital Pharmacies are different in each Pharmacy Service and vary by catheter type, so there is a high variability of combinations at different concentrations.…”

Antimicrobial lock solutions for implantable central venous devices: stability of vancomycin solutions

“…Dado que las bacterias que conforman el biofilm son 100-1.000 veces más resistentes a la acción de los antibióticos que las bacterias circulantes, la erradicación de dichas infecciones precisan del uso de concentraciones supraterapéuticas de antibiótico que permanezcan en contacto con el reservorio durante horas-días, en forma de sellados (11)(12)(13)(14)(16)(17)(18)(19)(20)(21)(22).…”