Compatibility, Stability, and Efficacy of Vancomycin Combined With Gentamicin or Ethanol in Sodium Citrate as a Catheter Lock Solution

Abstract

Indwelling catheters deliver lifesaving medical treatments for many chronically ill patients but are frequently a source of infection. Treatment may include an antimicrobial agent(s) and anticoagulant solution dwelling within the catheter. In vitro determinations of solution compatibility and stability are necessary prior to use in patients. The aim of this study was to determine the physical compatibility, chemical stability, and antimicrobial activity of vancomycin (5 or 10 mg/mL) with gentamicin (1 mg/mL) or 40% ethanol in 4% sodium citrate lock solution over 72 hours. All solutions were prepared per manufacturer's instructions. Samples were studied under 4 conditions: (1) 25°C with light, (2) 25°C without light, (3) 37°C with light, and (4) 37°C without light. Physical compatibility and chemical stability were assessed at 0, 24, 48, and 72 hours. Antimicrobial susceptibility testing was conducted at 0 and 72 hours. All studies were carried out in triplicate. All solution combinations under each condition remained patent from baseline to 48 hours. One solution combination of vancomycin (5 mg/mL) and ethanol (40% v/v) in 4% sodium citrate revealed a slight turbidity at 72 hours. Clarity and pH remained stable in all other solutions during the entire study period. Chemical compatibility and antibiotic activity ranged from 95% to 105% and 95% to 106% of initial baseline values, respectively, for all solutions under 4 storage conditions. All antibiotic-anticoagulant lock solutions were found to be physically, chemically, and microbiologically stable during the 72-hour study period except vancomycin (5 mg/mL) and ethanol (40% v/v) in 4% sodium citrate solution which showed slight turbidity at 72 hours.

Physical Compatibility, Antimicrobial Activity, and Stability of Cefazolin Combined with Gentamicin or Ethanol in Sodium Citrate as a Catheter Lock Solution

“…Our decision to study the admixture combinations, concentrations, and dwell times were based on our previous studies, a review of published literature and the IDSA clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update. [ 3 7 8 ] We chose to study cefazolin with sodium citrate as previous studies have examined cefazolin with heparin. [ 13 14 15 ] Moreover, citrate-based solutions have demonstrated improved clinical outcomes compared to heparin-based solutions.…”

“…Our previous studies incorporated ethanol into admixtures with antimicrobial agents and sodium citrate 4% to determine if this additive altered compatibility, antimicrobial susceptibility or stability. [ 7 8 ] Instillation of alternative solutions as a catheter lock solution may offer an option for clinicians combatting limited vascular access and increasing antimicrobial resistance. In addition to systemic antimicrobials, catheter lock solutions may extend catheter life for patients reliant on a catheter for their treatments.…”

“…Based on our previous studies, examining ethanol and commercially available sodium citrate 4% compatibility, we hypothesized the maximum concentration for ethanol was 40% when used with an antimicrobial agent with or without sodium citrate 4%. [ 7 8 ]…”

“…Previous studies have demonstrated in vitro compatibility of antimicrobial agents and sodium citrate with or without ethanol. [ 7 8 ] Cefazolin, a first-generation cephalosporin is frequently administered systemically to patients with methicillin sensitive gram-positive infections. The national health-care safety network reports the most common bloodstream infection in patients receiving HD was Staphylococcus aureus and that approximately 60% of these infections were methicillin-sensitive organisms.…”

“…This value was selected based on our past experience and the instrument sensitivity. [ 8 9 ] The pH of admixtures was measured using a pH meter (Accumet AB15, Fisher Scientific, Pittsburgh, PA). Before every use, the pH meter was calibrated using standard buffer solutions of pH 4.0, 7.0 and 10.0.…”