Vancomycin is still the main antibiotic for treating serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Traditionally, therapeutic drug monitoring (TDM) used trough serum concentrations as a marker for effectiveness and safety. However, recent evidence shows that monitoring trough levels can lead to higher kidney damage and often does not predict drug exposure accurately. As a result, the 2020 consensus guidelines recommended using area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC)-guided dosing as the best approach for optimizing vancomycin therapy. AUC-guided monitoring allows for personalized dosing by combining pharmacokinetic and pharmacodynamic principles, improving effectiveness while reducing harmful kidney effects. Bayesian forecasting software and first-order pharmacokinetic methods have also made it easier to apply AUC-guided dosing in various clinical settings. This review summarizes the current evidence on AUC-guided vancomycin therapeutic drug monitoring, focusing on pharmacokinetic principles, clinical effectiveness, kidney damage outcomes, implementation strategies, and new innovations. We evaluated literature published from January 2020 to June 2026 using electronic databases such as PubMed, Scopus, Embase, Web of Science, and Google Scholar. We critically assessed recent systematic reviews, meta-analyses, randomized studies, observational research, and international clinical practice guidelines. Current evidence consistently shows that AUC-guided dosing achieves similar or better clinical effectiveness while significantly decreasing vancomycin-related kidney injury compared to traditional trough-based monitoring. Nevertheless, broader implementation is limited by restricted access to Bayesian software, a lack of institutional resources, variability in lab support, and the need for specialized training for clinicians. New developments in artificial intelligence, machine learning, model-informed dosing, and electronic health record integration could further improve personalized vancomycin therapy. Ongoing collaboration among infectious disease doctors, clinical pharmacists, microbiologists, and pharmacometricians will be crucial to maximize the clinical benefits of AUC-guided therapeutic drug monitoring.
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