Abstract
Background: To promote model-informed precision dosing (MIPD) for vancomycin (VCM), we developed statements for therapeutic drug monitoring (TDM). Methods: Ten clinical questions were selected. The committee conducted a systematic review and meta-analysis as well as clinical studies to establish recommendations for area under the concentration-time curve (AUC)-guided dosing. Results: AUC-guided dosing tended to more strongly decrease the risk of acute kidney injury (AKI) than trough-guided dosing, and a lower risk of treatment failure was demonstrated for higher AUC/minimum inhibitory concentration (MIC) ratios (cut-off of 400). Higher AUCs (cut-off of 600 μg·h/mL) significantly increased the risk of AKI. Although Bayesian estimation with two-point measurement was recommended, the trough concentration alone may be used in patients with mild infections in whom VCM was administered with q12h. To increase the concentration on days 1–2, the routine use of a loading dose is required. TDM on day 2 before steady state is reached should be considered to optimize the dose in patients with serious infections and a high risk of AKI. Conclusions: These VCM TDM guidelines provide recommendations based on MIPD to increase treatment response while preventing adverse effects.
Highlights
Vancomycin has been widely used to treat infections caused by methicillin-resistantStaphylococcus aureus (MRSA) [1,2,3,4,5]
Ye et al conducted a systematic review of 12 guidelines for vancomycin therapeutic drug monitoring (TDM) using the Appraisal of Guidelines for Research & Evaluation infusionrelated reactions (II) [12], and a consensus guideline developed by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases
Because randomized controlled trials (RCTs) on the practice of TDM is difficult to perform, ranking recommendations and evidence levels adopted in the guidelines were made using the modified Minds classification (Table 1)
Summary
Vancomycin has been widely used to treat infections caused by methicillin-resistantStaphylococcus aureus (MRSA) [1,2,3,4,5]. Vancomycin treatment is associated with several adverse effects such as acute kidney injury (AKI) [6,7,8] and ototoxicity [9,10]. Trough concentrations of 15–20 μg/mL were recommended as the surrogate of AUC/MIC > 400 excluding MIC = 2 μg/mL for the treatment of complicated infections [13]. To promote model-informed precision dosing (MIPD) for vancomycin (VCM), we developed statements for therapeutic drug monitoring (TDM). The committee conducted a systematic review and meta-analysis as well as clinical studies to establish recommendations for area under the concentration-time curve (AUC)-guided dosing. TDM on day 2 before steady state is reached should be considered to optimize the dose in patients with serious infections and a high risk of AKI
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