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Updated: Aug 22, 2025
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
A Canadian perspective on the revised 2020 ASHP-IDSA-PIDS-SIDP guidelines for vancomycin AUC-based therapeutic drug
Jackson J Stewart1, Sarah Cj Jorgensen2, Linda Dresser3,4
1Pharmacy Department, Alberta Health Services, Edmonton, Alberta, Canada.
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.
Insights
Area-under-the-curve (AUC) vancomycin therapeutic drug monitoring (TDM) is not recommended for Canadian hospitals. Current evidence suggests trough-based TDM with reduced targets is safer and more practical for managing methicillin-resistant Staphylococcus aureus infections.
Area of Science:
- Pharmacology
- Infectious Diseases
- Clinical Pharmacy
Background:
- A revised guideline suggests shifting from trough to area-under-the-curve (AUC) for vancomycin therapeutic drug monitoring (TDM) in serious methicillin-resistant Staphylococcus aureus (MRSA) infections.
- This shift is endorsed by numerous American pharmacy and medical societies.
Purpose of the Study:
- To critically appraise recent literature on AUC-guided TDM for vancomycin.
- To determine the appropriateness of AUC TDM for Canadian hospital practice.
Main Methods:
- Literature review and critical appraisal of recent studies.
- Evaluation of evidence for efficacy, safety, and resource implications of AUC TDM versus trough TDM.
Main Results:
- Previous guidelines recommended trough levels of 15-20 mg/L for MRSA infections, with limited evidence.
- Aggressive trough targets have led to increased toxicity; AUC TDM is proposed as an alternative, but evidence for outcome benefits is low quality.
- Implementing AUC TDM requires significant resources and the causal link between AUC TDM and improved outcomes is not consistently demonstrated. Trough levels and AUC correlate highly, and lower trough targets can reduce toxicity.
Conclusions:
- Significant concerns exist regarding the adoption of AUC TDM for vancomycin in Canadian routine practice.
- Trough-based monitoring, with a modest reduction in target levels, remains the most evidence-informed practice currently available.
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