Stability of Trisodium Citrate and Gentamicin Solution

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INTRODUCTION

Catheter-related infections are a major problem for hemodialysis patients with central venous catheters for vascular access. Bacteremia may result from microorganisms entering the bloodstream at the catheter insertion site or from contamination of the catheter lumen. Various strategies may be used to prevent this complication, including aseptic precau­tions when manipulating or accessing the catheter and scrupu­lous hygiene of the skin around the catheter exit site.

The formation of a bacterial biofilm on the wall of the catheter lumen has been implicated in catheter colonization. In most cases of catheter-related bacteremia, treatment with systemic antibiotics alone is insufficient to resolve the infection, because the biofilm provides a nidus for infection and recurrent bacteremia. The affected catheter must usually be removed, but in selected cases a lock solution containing both an antibiotic and an anticoagulant is instilled into the catheter lumen. This approach results in a cure in about two-thirds of cases of catheter-related bacteremia, thus avoiding the risks and costs associated with replacing the catheter. Lock solutions are used to maintain the patency of the catheter between hemodialysis sessions, and several recent publications have supported the use of antibiotic—anticoagulant lock solutions to reduce the rate of catheter-related infection.
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Heparin is an anticoagulant that is commonly used for maintaining catheter patency, but citrate has also been shown to be effective in this respect; furthermore, at concentrations of about 30%, citrate has shown some antimicrobial activity. Although locking solutions containing a high concentration of citrate are effective, they are not used in North America, because of concerns about patient safety, particularly the possibility of cardiac arrest. Investigations of lower-concentra­tion citrate lock solutions demonstrated that a solution containing 4% trisodium citrate (40 mg/mL) was both effective and safe.

A number of antibiotics, including vancomycin and gentamicin, have been used in lock solutions. At present, gentamicin appears to be acceptable for this purpose, and it has been used in combination with citrate as a lock solution. With gentamicin-containing solutions, catheter-related infection rates decreased from about 4 episodes per 1000 catheter days to 0.3 episodes per 1000 catheter days.

A mixture of gentamicin and citrate suitable for use as a locking solution is not available commercially, so it must be compounded from commercially available components. Efficiencies in terms of time and cost can be achieved by preparing and storing such solutions in advance of their use, but information regarding the product’s stability is required. In one stability study, in which commercial 46.7% trisodium citrate solution was used to extemporaneously prepare a 4% solution, there was no change in concentration after 28 days of storage in plastic syringes at room temperature. Although the compatibility of a gentamicin—citrate solution has been studied, the findings were of limited value since the investiga­tors only examined the solutions for visual changes over time; they did not measure the concentrations of the components. canada pharmacy mall

This type of admixture prepared in quantity would be considered to have a medium risk of microbial contamination. USP Chapter <797> would assign an expiration period of 30 h at room temperature and 7 days with refrigeration. However, expiration periods can be expanded if published data showing compatibility and stability of the product are available and sterility testing is performed. Therefore, the purpose of this stability study was to determine whether an extemporaneous preparation of a gentamicin—citrate catheter lock solution pack­aged in prefilled syringes retained its potency over a reasonable period of time, to allow for advance preparation and storage of the solution.

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