Vancomycin Dosing in Patients on Intermittent Hemodialysis—A Retrospective Study

Purpose

To determine the incidence of therapeutic target attainment using a three-times per week protocol for vancomycin therapy given during the last hour of intermittent hemodialysis (HD).

Methods

A single-center retrospective cohort study was conducted of patient medical records in a remote dialysis center from January 2017 to July 2023. Adult patients with chronic kidney disease stage 5 on ≥3 months of intermittent HD who had received a course of vancomycin therapy with ≥1 serum vancomycin concentration recorded were included. Demographic and dosing data were collected. Clinician adherence with the dosing protocol and attainment of the therapeutic target (trough concentration within 15–20 mg/L) following the loading and maintenance doses were assessed. Factors associated with target nonattainment following the loading dose were analyzed, and the 48- and 72-h maintenance dosing intervals were analyzed for target nonattainment.

Findings

A total of 98 vancomycin courses (67 patients) were available for analysis. Only 38% of the loading doses were prescribed as per protocol. Following the loading dose, 25% of trough concentrations achieved the therapeutic target concentration (15–20 mg/L), 25% returned a supra-therapeutic concentration (>20 mg/L) and 50% were sub-therapeutic (<15 mg/L). When compared with those achieving target, sub-therapeutic concentrations were associated with a lower loading dose (median 16.6 vs 20.0 mg/kg, P < 0.002), and supra-therapeutic concentrations had a shorter dosing interval between the loading dose and first maintenance dose (median 31.5 vs 39.0 h, P = 0.06). Of the 201 maintenance trough concentrations collected, 65% were therapeutic, 21% were sub-therapeutic and 14% were supra-therapeutic, with an overall median trough concentration of 17.3 mg/L. As the treatment duration increased, an increase was seen in the number of dose adjustments required to achieve the target trough concentration. The 48-h dosing interval was associated with more supra-therapeutic concentrations and the 72-h interval was associated with more sub-therapeutic concentrations (df = 2, P = 0.022).

Implications

We have identified a high rate of target nonattainment for HD patients on a three times a week vancomycin dosing regimen. We recommend a loading dose of 20 to 25 mg/kg irrespective of the indication and a better-defined dosing interval after the loading dose. A higher maintenance dose should be prescribed when the time to next dialysis session is 72 h. Further pharmacokinetic studies are needed to assess factors influencing target concentration attainment following the maintenance doses and to determine an optimal dosing regimen.