Vancomycin area under the curve to minimum inhibitory concentration ratio predicting clinical outcome: a systematic review and meta-analysis with pooled sensitivity and specificity

Abstract

Background: Vancomycin is a first-line antibiotic for methicillin-resistant Staphylococcus aureus infections or other Gram-positive infections. The area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is proposed as a therapeutic drug-monitoring parameter. How well clinical efficacy is predicted by this measure has not been established. Objective: Determine the test performance characteristics (TPC) of AUC:MIC of vancomycin for prediction of positive outcome. Data Sources: PubMed and Ovid Medline (1946Medline ( to 2018 and EMBASE (1974EMBASE ( to 2018. Study Eligibility Criteria and Participants: Studies of patients treated with vancomycin for any type of infection in peer reviewed publications. All patient populations were included. Interventions: Vancomycin AUC:MIC or AUC was related to patient clinical outcome. Methods: Searches of medical databases using relevant terms were performed. Screening, study reviewing, data extracting and assessing data quality was performed independently by two reviewers. Studies were stratified by type of primary outcome for calculation of pooled sensitivity, specificity and construction of hierarchical summary receiver operating characteristic (HSROC) curves. Results: Nineteen studies including 1699 patients were meta-analysed. Pooled sensitivity and specificity were 0.77 (95% CI 0.67e0.84) and 0.62 (95% CI 0.53e0.71) respectively for the seven studies with primary outcome of mortality and 0.65 (95% CI 0.53e0.75), 0.58 (95% CI 0.48e0.67) for studies with composite or clinical cure outcome (n ¼ 12). HSROC curves suggested considerable heterogeneity. An additional 11 studies were described but could not be included for meta-analysis because data were not available. The majority of these studies (9/11) failed to demonstrate a relationship between AUC:MIC and positive clinical outcome. Conclusions: Vancomycin AUC:MIC performance was modest and inconsistent. Analysis was limited by studies without sufficient data; therefore, meta-analytic results may overestimate TPC values. Given this, as well as the lack of standardization of methods, widespread adoption of AUC:MIC as the preferred vancomycin monitoring parameter may be premature.

The monitoring of vancomycin: a systematic review and meta-analyses of area under the concentration-time curve-guided dosing and trough-guided dosing

“…The target AUC values and trough concentrations in each study incorporated into this meta-analysis differed. Dalton et al concluded that it was difficult to calculate the optimal target AUC/MIC as the AUC estimation method and study background varied among the studies [6]. In the future, a comparative trial of AUC-guided vs. trough-guided monitoring with appropriately defined target AUC values and trough concentrations is needed to determine if AUC-guided monitoring lowers the risk of mortality and AKI.…”

“…The practice guidelines for TDM of VCM recommended an AUC/MIC ratio of ≥400 to predict the clinical efficacy of VCM against MRSA (MIC ≤1 μg/mL) [4,5]. However, Dalton et al reported that the target AUC/MIC could not be calculated that related to the effectiveness and safety of VCM [6]. Therefore, the target AUC/MIC value, which is an indicator of effectiveness in MRSA infection therapy, is still controversial.…”

Comparison of Vancomycin Area-Under-the-Curve Dosing Versus Trough Target–Based Dosing in Obese and Nonobese Patients With Methicillin-Resistant Staphylococcus aureus Bacteremia

“…It is important to note that this specific AUC target is based on limited study data and that a recent meta-analysis found only modest ability of similar AUC:MIC measures (including slightly less than and greater than 400 mg h/L) at predicting clinical outcomes. 27 Nevertheless, implementation of an AUC dosing strategy will ideally target daily AUC 24 values slightly greater than 400 mg h/L, whereas a generally acceptable clinical AUC range between 400 and 560 to 600 mg h/L has been supported in various studies. 28,29 Therefore, slightly more modest reductions in TDD may be warranted when moving from a trough-based to AUC-based dosing strategy in obese patients.…”

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

“…However, response to drug therapy is inherently unpredictable and multifactorial (10). Therefore, although 'defined' optimal values for VAN pharmacokinetic-pharmacodynamic (PK-PD) parameters have been promoted, a great deal of uncertainty still exists, and breakpoints for efficacious AUC:MIC values in retrospective studies range widely from 211 to 660 (11). Consideration of patient goals, condition, and response has a major role when adapting the general TDM target for specific patient needs (12).…”