The revised consensus guidelines for dosing and monitoring vancomycin are an updated version of the 2009 guidelines developed by the American Society of Health-Systems Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists Vancomycin Guidelines Committee. The following is an executive summary of key recommendations contained in this document [1]. The grading system for evaluating the literature can be found in Table 1. Grading System for Recommendations Based on Quality of Evidence Adapted from the Canadian Task Force on the Periodic Health Examination [2]. Grading System for Recommendations Based on Quality of Evidence Adapted from the Canadian Task Force on the Periodic Health Examination [2]. Despite more than 61 years of clinical use of vancomycin, knowledge gaps regarding the most appropriate approach for optimizing therapy and minimizing toxicity still exist. The area under the curve over 24 hours to minimum inhibitory concentrations (AUC/MIC) has been documented as the primary pharmacokinetic/pharmacodynamic (PK/PD) target for glycopeptides, including vancomycin. The previous consensus guidelines in 2009 recommended the use of trough monitoring (target, 15–20 mg/L) as a surrogate marker of the AUC/MIC (target 400 mg × h/L) for ease of managing therapy and simplifying dose adjustments and monitoring. At that time, the primary reason for increasing the exposure of vancomycin via specific trough monitoring targets was to improve the likelihood of achieving the AUC/MIC target of 400 mg × h/L and thereby increase efficacy. However, since implementation of these recommendations, there have been numerous reports of increased nephrotoxicity in adults and pediatric patients when trough level monitoring using these targets has been applied. Recent PK/PD and toxicodynamic studies have demonstrated a significant reduction in vancomycin exposure and nephrotoxicity rates when AUC/MIC monitoring has been used vs traditional trough monitoring approaches. When AUC/MIC-guided empiric dosing is used, the MIC should be assumed to be 1 mg/L based on broth microdilution methods, extensive antibiotic susceptibility data, and the inaccuracies or variability of automated susceptibility testing (±1 log2 dilutions). Specific information regarding MIC evaluation and automated susceptibility testing can be found under the MIC susceptibility section of the full guidelines [1]. A target AUC between 400 and 600 mg × h/L is suggested for methicillin-resistant Staphylococcus aureus (MRSA) invasive infections in adults and pediatric patients based on clinical efficacy and safety data. These AUC targets should be evaluated early in the course of treatment (24–48 hours) given the importance of early and appropriate therapy. Loading doses based on actual body weight are suggested for patients who are critically ill, require renal replacement therapy, or are receiving continuous infusion therapy. Specific recommendations for patients with obesity on renal replacement therapy and, for the first time, pediatric patients are now included in the revised guidelines [1]. It should be noted that almost all data available on vancomycin PK/PD and toxicodynamics have been derived from patients who have been treated for serious MRSA infections. Further, the majority of the data have been derived from patients with complicated bloodstream infections. Therefore, caution should be applied when extrapolating this information to mild noninvasive infections or other bacterial species susceptible to vancomycin. These guidelines conclude that AUC-guided dosing and monitoring are the most accurate and safest ways to dose vancomycin. The recommendations in this document should not circumvent sound clinical judgment in managing patients who require vancomycin therapy (Table 2). Specific details for each section of the document, including references, can be found in the primary publication [1]. Primary Recommendations for Vancomycin Dosing and Therapeutic Drug Monitoring Abbreviations: AKI, acute kidney injury; AUC, area under the curve; BMD, broth Micro Dilution, clearance; CL, CRRT, continuous renal replacement therapy; MIC, minimum inhibitory concentration; MRSA, methicillin-resistant Staphylococcus aureus; PK, pharmacokinetic. Primary Recommendations for Vancomycin Dosing and Therapeutic Drug Monitoring Abbreviations: AKI, acute kidney injury; AUC, area under the curve; BMD, broth Micro Dilution, clearance; CL, CRRT, continuous renal replacement therapy; MIC, minimum inhibitory concentration; MRSA, methicillin-resistant Staphylococcus aureus; PK, pharmacokinetic. The complete vancomycin guideline paper can be cited and accessed at: https://academic.oup.com/ajhp/advance-article/doi/10.1093/ajhp/zxaa036/5810200 Financial support. A. W.-B. received a grant from Merck & Co. and consulted for Rempex Pharmaceuticals, INSMED, Merck & Co., Nabriva Therapeutics, GlaxoSmithKline, Paratek Pharmaceuticals, Achaogen, Inc., Bayer HealthCare, and SIGA Technologies. J. B. served on a planning committee for the US Food and Drug Administration and European Medicines Agency at the American College of Clinical Pharmacy’s annual meeting; participated in the design of a pediatric clinical trial; served on an executive committee for the United States Committee on Antimicrobial Susceptibility Testing; and consulted for Achaogen, Allergan, ContraFect, GlaxoSmithKline, Janssen, Melinta, Merck, Nabrive, Pfizer, Theravance, and Zavante. C. L. received a research grant from Nohla Therapeutics and was a member of an Independent Efficacy Adjudication Committee with Theravance. J. L. received research awards from the Sternfels Prize for Drug Safety Innovation, Duke University, the National Institutes of Health (NIH) and National Institute of Child Health and Human Development, and JMI Laboratories; was an invited advisory board member for FDA, the Asian Pacific Health Foundation, and Infectious Diseases and Therapy journal. D. L. served on the data safety monitoring board for Contrafect and served on an adjudication panel for Novartis. T. L. received grants from the Antibiotic Resistance Leadership Group (ARLG), Merck & Co, and Motif Bio PLC; served as a health outcomes project consultant for Paratek Pharmaceuticals, Allergan, Merck & Co., and Melinta Therapeutics; served on advisory boards for Paratek Pharmaceuticals, Motif Bio PLC, Achaogen, Nabriva, and Tetraphase; served as a consultant to Paratek Pharmaceuticals, ARLG, Allergan, Merck & Co., Melinta Therapeutics, Motif Bio PLC, Achaogen, Nabriva, and Tetraphase; and was a speaker for Melinta Therapeutics, Tetraphase, and Sunovion. H. M. served as an international working group member for the European Cystic Fibrosis Society and North American Cystic Fibrosis Society, served on an advisory panel for the Centers for Disease Control and Prevention and Pew Charitable Trust, and was on a committee for the Arkansas Health Department. M. B. received research grants from Merck & Co. and Hope Pharmaceutical and served on an advisory board for NxStage and Baxter. M. P. received a grant from Merck, Inc., served on an advisory board for Shinogi and Paratek Pharmaceuticals, and served on the meet the professor program for Merck. K. R. received a grant from Theravance Biopharm, NIH, ARLG, and Allergan; consulted for BLC, Entasis, Merck, Paratek Pharmaceuticals, Shionogi, Tetraphase, and Wockhardt; was a speaker at the American Society for Microbiology and European Society for Clinical Microbiology and Infectious Diseases ASM/ESCMID conference; served on the 2015–2019 Program Committee and was 2016–2018 Program Co-Chairperson for the American Microbiology Society; and was a member of the 2017–2019 Antimicrobial Resistance Committee for IDSA. M. J. R. received research grants from Bayer Pharmaceuticals, the NIH Research Project Grant (RO1) Program, Merck, Allergan, the Michigan Department of Health and Human Services, Accelerate Diagnostics, Inc., NIH, Contrafect, Motif Biosciences, and the Michigan Translational Research and Commercialization Program; and served as a grant review panel member for NIH. The other authors have declared no potential conflicts of interest. Potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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