Vancomycin dosing in patients on intermittent haemodialysis – a retrospective study

<p>Background: Vancomycin is commonly used to treat<br>methicillin-resistant Staphylococcus aureus in haemodialysis<br>patients with the approach to dosing often based on locally<br>developed protocols. This places haemodialysis patients at<br>risk of receiving suboptimal loading doses and/or<br>maintenance doses which can result in therapeutic target<br>non-attainment, treatment failure and development of<br>vancomycin resistance.<br>Purpose: To determine the incidence of therapeutic target<br>attainment using a three-times weekly locally developed<br>protocol for intradialytic vancomycin therapy.<br>Methods: A retrospective study was conducted of medical<br>records in a remote Australian dialysis centre from January<br>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.<br>Demographic and dosing data were collected. Clinician<br>adherence with the dosing protocol and attainment of the<br>therapeutic target (trough concentration 15-20 mg/L)<br>following the loading dose and maintenance doses were<br>assessed. Factors associated with target non-attainment<br>following the loading dose were also analysed.<br>Results: A total of 98 vancomycin courses (67 patients) were<br>available for analysis. Only 38% of the loading doses were<br>prescribed as per protocol. Following the loading dose, 25%<br>of trough concentrations achieved the therapeutic target<br>concentration, 50% were sub-therapeutic and 25% were supra-therapeutic. When compared with those achieving target, sub-therapeutic concentrations were associated with<br>a lower loading dose (median 16.6 mg/kg vs 20.0.mg/kg, p <<br>0.002), and supra-therapeutic concentrations had a shorter<br>dosing interval between the loading dose and first<br>maintenance dose (median 31.5 hours vs 39.0 hours, p =<br>0.06). Of the 201 maintenance trough concentrations<br>collected, 65% were therapeutic, 21% were sub-therapeutic<br>and 14% were supra-therapeutic with an overall median<br>trough concentration of 17.3mg/L. As the treatment duration increased, the number of dose adjustments required to<br>achieve the target trough concentration increased. A similar<br>incidence of target attainment was achieved between the 48-<br>hour dosing interval and 72-hour interval. However, more<br>subtherapeutic concentrations occurred during the 72-hour<br>dosing interval, and more supratherapeutic concentrations<br>occurred in the 48-hour dosing interval, df=2, p = 0.022.<br>Conclusion: The vancomycin dosing protocol does not<br>consistently achieve the vancomycin target trough<br>concentration following the loading dose or reliably maintain<br>the target trough concentrations following the maintenance<br>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.</p>