A Canadian perspective on the revised 2020 ASHP–IDSA–PIDS–SIDP guidelines for vancomycin AUC-based therapeutic drug monitoring for serious MRSA infections

Abstract

Background: A revised consensus guideline on therapeutic drug monitoring (TDM) of vancomycin for serious methicillin-resistant Staphylococcus aureus (MRSA) infections was recently published with endorsement of numerous American pharmacy and medical societies. Changing practice from trough TDM to area-under-the-curve-(AUC)-guided dosing was suggested. Methods: Recent literature was critically appraised to determine whether AUC TDM is appropriate for Canadian hospital practice. Results: Previous 2009 vancomycin consensus guidelines recommended trough levels of 15–20 mg/L for serious MRSA infections, based on relatively poor evidence for efficacy or safety. In the past decade, aggressive trough targets have led to unnecessary toxicity. Adoption of a TDM strategy using an alternative parameter (AUC) has been suggested, although the evidence for any outcome benefits is low quality. In addition, implementation would require greater resources at health care institutions in the forms of more frequent serum levels or acquisition of costly Bayesian software programs. Most studies on this subject have been observational and retrospective; therefore, relationships between TDM parameters and outcomes have not been convincingly and consistently demonstrated to be causal in nature. Despite claims to the contrary, based on few in silico experiments, available clinical data suggest correlation of trough levels and AUC is high. TDM with lower target trough levels is a simpler solution to reduce risk of toxicity. Conclusions: There are serious concerns with adoption of AUC TDM of vancomycin into routine practice in Canada. Trough-based monitoring with modest reduction in target levels remains the most evidence-informed practice at this time.

Optimal Practice for Vancomycin Therapeutic Drug Monitoring: Position Statement From the Anti-infectives Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology

“…The relationship between steady-state trough concentrations and AUC 24 was examined based on the known pharmacokinetic properties of vancomycin. 30 Consistent with previous clinical studies, 31 although there is a significant association between the pharmacokinetic parameters (R 2 , 0.409), substantial variability exists (Fig. 2) such that for target trough concentrations within the 15-20 mg/L range, AUC 24 values are predicted to range from approximately 400-1800 mg.h/L across the patient population.…”

Pharmacokinetic equations versus Bayesian guided vancomycin monitoring: Pharmacokinetic model and model‐informed precision dosing trial simulations

“… 1 Trough monitoring is preferred in certain settings according to a Canadian perspective on the revised guideline. 4 …”

“…The revised guideline, however, acknowledges difficulties determining steady‐state conditions in clinical practice, being subject to variables such as changing renal function and loading dose 1 . Trough monitoring is preferred in certain settings according to a Canadian perspective on the revised guideline 4 …”

“…1 Trough monitoring is preferred in certain settings according to a Canadian perspective on the revised guideline. 4 Utilizing pharmacokinetic and/or pharmacodynamic (PK) models to optimize, guide, and individualize dosing using patients' covariates and drug concentrations is referred to as model-informed precision dosing (MIPD), Bayesian forecasting, or model-based precision dosing. [5][6][7] Reports exist suggesting MIPD (e.g., using Bayesian programs) can outperform clinician judgment in recommending vancomycin dosing regimens.…”

Systematic Comparison of Hospital-Wide Standard and Model-Based Therapeutic Drug Monitoring of Vancomycin in Adults

“…Despite this recommendation, the pharmacokinetic/pharmacodynamic (PK/PD) index of interest that should be used to guide vancomycin dosing is still under debate [ 4 , 5 , 6 , 7 ]. Some argue that the evidence for using AUC/MIC-based TDM over the monitoring of vancomycin concentrations is inconclusive and that it is too early to justify the increased resource use associated with AUC/MIC monitoring [ 4 , 6 , 8 ]. As a result, there has not been a universal application of AUC/MIC-based TDM of vancomycin to date, and single vancomycin concentrations are still regularly used to guide dosing.…”