Vancomycin Dosing in High Flux Hemodialysis
Purpose. The feasibility of using a limitedsampling algorithm for administration of vancomycin for treatment of vascular-access-related bacteremia in outpatient high flux hemodialysis was investigated.
Methods. The original vancomycin-dosing algorithm used at our hemodialysis unit required stat orders for serum vancomycin concentrations before each hemodialysis session to determine the dose of vancomycin to be administered posthemodialysis. Vancomycin concentration data obtained using this original algorithm from January through September 2001 were retrospectively analyzed to determine how many vancomycin concentrations measured 5-20 µg/mL and identify potential clinical predictors of vancomycin removal.
Results. A total of 409 serum vancomycin concentrations were drawn during the study period. Ninety-seven percent of concentrations drawn were within 5-20 µg/mL. Twenty-eight patients had data evaluable to determine pharmacokinetic parameters. Mean ± S.D. vancomycin removal was 39% ± 13%. Body weight and duration of dialysis alone, blood flow rate, and dialysate flow rate were not predictive of vancomycin removal. Based on these data, a revised algorithm with limited vancomycin sampling data was initiated in December 2002. Retrospective analysis of concentrations obtained and achieved by this algorithm demonstrated a 70% reduction in the number of vancomycin concentration determinations, with 93% of these concentrations within 5-20 µg/mL. The estimated annual cost saving to the hemodialysis unit with the revised algorithm was $7552.
Conclusion. A vancomycin-dosing algorithm using limited concentration monitoring for hemodialysis patients achieved comparable vancomycin concentrations to those found with more frequent monitoring and resulted in significant cost savings.

Infection is the second leading cause of death among patients with end-stage renal disease (ESRD) in the United States. Frequent manipulation of the vascular-access site to perform hemodialysis increases these patients' risk of infection with gram-positive organisms. Vancomycin, a glycopeptide antibiotic, is commonly used to treat gram-positive pathogens associated with vascular-access-related infections, such as coagulase negative Staphylococcus species, methicillin-resistant Staphylococcus aureus, and methicillin-sensitive S. aureus in patients with severe allergies to penicillin. Vancomycin is excreted primarily by glomerular filtration, and its elimination half-life is prolonged to 54-180 hours in patients with ESRD. The removal of drugs and solutes by hemodialysis depends partly on the molecular weight of the compound. Conventional hemodialysis with cuprophane and cellulose acetate membranes has a limited capacity to remove substances larger than 500 Da. Because vancomycin has a molecular weight of approximately 1500 Da, it is only marginally removed by conventional hemodialysis, which allows for very long dosing intervals (i.e., single weekly doses). However, higher permeability (high flux) membranes, such as polysulfone, clear 25-50% of the drug.

Several strategies have been proposed to appropriately dose vancomycin in high flux hemodialysis. Intradialytic administration of vancomycin during the last one to two hours of each hemodialysis session has been proposed to simplify administration in the outpatient hemo-dialysis clinic setting. Because significant amounts of vancomycin are removed during high flux hemodialysis, larger doses need to be administered to sustain plasma vancomycin concentrations above the minimum inhibitory concentration (MIC) of the microorganisms. Frequent monitoring of vancomycin concentrations is recommended with this technique because of the variable effects of drug removal during hemo-dialysis. Recently, a strategy for once-weekly administration of vancomycin in high flux hemodialysis was proposed. The administration of higher doses of vancomycin (30 mg/kg) in the last two hours of hemodialysis achieved mean prehemo-dialysis plasma vancomycin concentrations of 11.7 ± 1.5 µg/mL in anuric patients on day 8. Drawbacks to this approach include unnecessarily high peak plasma drug concentrations (95.5 ± 19.9 µg/mL) and the increased need for monitoring serum vancomycin concentrations to en-sure that patients are not receiving a subtherapeutic dose, especially patients with residual renal function.

The administration of vancomycin after each hemodialysis session ensures consistent serum concentrations of vancomycin during the interdialytic period. Barth and DeVincenzo described a method by which 20 mg of vancomycin per kilogram was administered as a loading dose posthemodialysis, followed by 500 mg after each hemodialysis session. In patients receiving multiple doses of vancomycin, only 16% of the samples had a vancomycin concentration below 10 µg/mL after one week, compared with 84% of samples for patients receiving 20-mg/kg doses once weekly.

Based on the multidose data described by Barth and DeVincenzo and the low risk of vancomycin toxicity, we initiated a posthemodialysis vancomycin dosing algorithm in our outpatient hemodialysis unit for a 21-day course of treatment (nine hemodialysis sessions) for vascular-access-related bacteremia. The algorithm used prehemodialysis vancomycin concentrations for dosing and monitoring. The purpose of this study was to determine the number of predialysis vancomycin concentrations in the desired therapeutic range after a 1000-mg loading dose, followed by 500 mg administered posthemodialysis, and whether less frequent vancomycin monitoring was feasible. The original dosing algorithm ( Table 1 ) was used to identify potential clinical parameters that would be predictive of vancomycin removal. We also assessed the economic impact of simplified vancomycin monitoring procedures.