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.