Vancomycin dosing in patients on intermittent haemodialysis – a retrospective study

Background: Vancomycin is commonly used to treat
methicillin-resistant Staphylococcus aureus in haemodialysis
patients with the approach to dosing often based on locally
developed protocols. This places haemodialysis patients at
risk of receiving suboptimal loading doses and/or
maintenance doses which can result in therapeutic target
non-attainment, treatment failure and development of
vancomycin resistance.
Purpose: To determine the incidence of therapeutic target
attainment using a three-times weekly locally developed
protocol for intradialytic vancomycin therapy.
Methods: A retrospective study was conducted of medical
records in a remote Australian dialysis centre from January
2017 to July 2023. Adult patients with chronic kidney disease stage 5 on ≥3 months of intermittent haemodialysis and 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 15-20 mg/L)
following the loading dose and maintenance doses were
assessed. Factors associated with target non-attainment
following the loading dose were also analysed.
Results: 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, 50% were sub-therapeutic and 25% were supra-therapeutic. When compared with those achieving target, sub-therapeutic concentrations were associated with
a lower loading dose (median 16.6 mg/kg 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 hours vs 39.0 hours, 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 17.3mg/L. As the treatment duration increased, the number of dose adjustments required to
achieve the target trough concentration increased. A similar
incidence of target attainment was achieved between the 48-
hour dosing interval and 72-hour interval. However, more
subtherapeutic concentrations occurred during the 72-hour
dosing interval, and more supratherapeutic concentrations
occurred in the 48-hour dosing interval, df=2, p = 0.022.
Conclusion: The vancomycin dosing protocol does not
consistently achieve the vancomycin target trough
concentration following the loading dose or reliably maintain
the target trough concentrations following the maintenance
doses. Adherence to the loading dose protocol was shown to be suboptimal for prescribers, although adherence did not result in improved target trough concentration attainment, with most achieving a sub-therapeutic trough concentration. The recommendations from this study are to sustain the current loading dose of 25mg/kg and implement the weight-based loading dose for all indications with the removal of the current protocol dosing cap for certain conditions. When prescribing a loading dose and determining the maintenance doses, the time to the next dialysis session should also be considered, especially in those with residual renal function.