Evaluation of compatibility and stability of daptomycin in an antibiotic-anticoagulant lock solution

Purpose:  To evaluate the in vitro stability and compatibility of daptomycin in novel antimicrobial-anticoagulant combination lock solutions.

Methods:  Candidate lock solutions included daptomycin(D) 1mg/mL in solution with different combinations of heparin(H), trisodium citrate(TSC), azithromycin(A) and/or gentamicin(G).  Lactated Ringer’s solution was added to provide a total volume of 5mL.   Chemical stability was assessed by a determination of degradation of the components of the admixture. Drug concentration was assessed via Waters Alliance HPLC using Phenomenex Luna C8(2), 150*2.6mm, 5µ column.  A gradient run was carried out 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 test solution was visually inspected for particulate matter and color change. Lock solutions were prepared in glass vials and tested in triplicate.

Results: Table 1. Daptomycin concentrations of test solutions at 48, 72 and 96 hours

Lock Solution	48 hours, %	72 hours, %	96 hours, %
D 1mg/mL + H 1,000 units/mL	101.18	98.33	83.99
D1mg/mL + H 100 units/mL	101.16	99.42	82.12
D 1mg/mL + TSC 28mg/mL (2.8%)	102.41	101.94	93.26
D 1mg/mL + A 5mg/mL + H 1,000 units/mL	101.79	101.84	91.45
D 1mg/mL + A 5mg/mL + H100 units/mL	101.54	100.33	101.36
D 1mg/mL + A 5mg/mL + TSC 28mg/mL (2.8%)	101.37	101.27	103.31
D 1mg/mL + G 3mg/mL	97.18	91.56	78.99
D 1mg/mL + G 3mg/mL + TSC 28mg/mL (2.8%)	90.66	86.69	81.55

Daptomycin concentrations were maintained ≥90% of baseline for all solutions at 48 hours. Gentamicin concentrations (not shown in table) remained ≥95% of baseline for the full 96-hour study period.

Conclusion:  This study confirms the stability and compatibility of daptomycin in combination with select antimicrobials and additives in lock solutions. The extended stability of ≥48 hours may allow for ease in preparation, longer catheter dwell times and less frequent exchanges without compromising in situ effectiveness.