Evaluation of traditional initial vancomycin dosing versus utilizing an electronic AUC/MIC dosing program
Background: Area under the curve to minimum inhibitory concentration (AUC/MIC) has been recommended by the 2020 updated vancomycin guidelines for dosing vancomycin for both efficacy and safety. Previously, AUC/MIC has been cumbersome to calculate so surrogate trough concentrations of 15-20 mg/dL were utilized. However, trough-based dosing is not a sufficient surrogate as AUC/MIC targets of 400-600 can usually be reached without achieving troughs of 15-20 mg/dL. Targeting higher trough levels may also lead to adverse events including acute kidney injury (AKI) and nephrotoxicity.
Objective: To compare the mean total first day vancomycin dose in traditional trough-based dosing versus dosing recommended by an AUC/MIC dosing program.
Methods: Adult inpatients who received at least 24 hours of IV vancomycin treatment were included in this single-center, retrospective cohort study. The primary endpoint was difference in mean total first day vancomycin dose in milligrams (mg) received between patients’ traditional trough-based dosing and recommended dose via AUC/MIC electronic dosing calculator. Patients served as their own control by analyzing both actual dose received and dose recommended by the electronic AUC/MIC program. Rates of vancomycin induced adverse events, including acute kidney injury, elevated steady-state trough concentrations, and Red Man’s syndrome were also compared between patients who received doses consistent with the AUC/MIC dosing recommendation versus those who did not.
Results: 264 patients were included in this study. Initial 24-hour vancomycin exposure was significantly lower with the recommended AUC/MIC dose versus the dose received (2380.7; SD 966.6 mg vs 2649.6; SD 831.8 mg, [95% CI 114.7:423.1] p=0.0007).
Conclusions: Utilizing an electronic AUC/MIC vancomycin dosing calculator would result in lower total first day vancomycin doses.
Rybak MJ, Le J, Lodise TP, Levine DP, Bradley JS, Liu C, Mueller BA, Pai MP, Wong-Beringer A, Rotschafer JC, Rodvold KA, Maples HD, Lomaestro BM. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2020;77(11):835-864. https://doi.org/10.1093/ajhp/zxaa036
Patel N, Pai MP, Rodvold KA, Lomaestro B, Drusano GL, Lodise TP. Vancomycin: we can't get there from here. Clin Infect Dis. 2011;52(8):969-974. https://doi.org/10.1093/cid/cir078
Mohr JF, Murray BE. Point: Vancomycin is not obsolete for the treatment of infection caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2007;44(12):1536-1542. https://doi.org/10.1086/518451
Pai MP, Neely M, Rodvold KA, Lodise TP. Innovative approaches to optimizing the delivery of vancomycin in individual patients. Adv Drug Deliv Rev. 2014;77:50-57. https://doi.org/10.1016/j.addr.2014.05.016
van Hal SJ, Paterson DL, Lodise TP. Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Antimicrob Agents Chemother. 2013;57(2):734-744. https://doi.org/10.1128/aac.01568-12
Linder A, Fjell C, Levin A, Walley KR, Russell JA, Boyd JH. Small acute increases in serum creatinine are associated with decreased long-term survival in the critically ill. Am J Respir Crit Care Med. 2014;189(9):1075-1081. https://doi.org/10.1164/rccm.201311-2097oc
Suzuki Y, Kawasaki K, Sato Y, Tokimatsu I, Itoh H, Hiramatsu K, Takeyama M, Kadota J. Is peak concentration needed in therapeutic drug monitoring of vancomycin? A pharmacokinetic-pharmacodynamic analysis in patients with methicillin-resistant staphylococcus aureus pneumonia. Chemotherapy. 2012;58(4):308-312. https://doi.org/10.1159/000343162
Lodise TP, Patel N, Lomaestro BM, Rodvold KA, Drusano GL. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis. 2009;49(4):507-514. https://doi.org/10.1086/600884
Zasowski EJ, Murray KP, Trinh TD, Finch NA, Pogue JM, Mynatt RP, Rybak MJ. Identification of Vancomycin Exposure-Toxicity Thresholds in Hospitalized Patients Receiving Intravenous Vancomycin. Antimicrob Agents Chemother. 2017;62(1):e01684-17. https://doi.org/10.1128/aac.01684-17
Neely MN, Youn G, Jones B, Jelliffe RW, Drusano GL, Rodvold KA, Lodise TP. Are vancomycin trough concentrations adequate for optimal dosing?. Antimicrob Agents Chemother. 2014;58(1):309-316. https://doi.org/10.1128/aac.01653-13
Heil EL, Claeys KC, Mynatt RP, Hopkins TL, Brade K, Watt I, Rybak MJ, Pogue JM. Making the change to area under the curve-based vancomycin dosing. Am J Health Syst Pharm. 2018;75(24):1986-1995. https://doi.org/10.2146/ajhp180034
ClinCalc. Vancomycin Calculator. Available at: https://clincalc.com/vancomycin/ (accessed Sep 5, 2020).
Covvey JR, Erickson O, Fiumara D, Mazzei K, Moszczenski Z, Slipak K, Nemecek BD, Zimmerman DE, Guarascio AJ. Comparison of Vancomycin Area-Under-the-Curve Dosing Versus Trough Target-Based Dosing in Obese and Nonobese Patients With Methicillin-Resistant Staphylococcus aureus Bacteremia. Ann Pharmacother. 2020;54(7):644-651. https://doi.org/10.1177/1060028019897100
Neely MN, Kato L, Youn G, Kraler L, Bayard D, van Guilder M, Schumitzky A, Yamada W, Jones B, Minejima E. Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing. Antimicrob Agents Chemother. 2018;62(2):e02042-17. https://doi.org/10.1128/aac.02042-17
Finch NA, Zasowski EJ, Murray KP, Mynatt RP, Zhao JJ, Yost R, Pogue JM, Rybak MJ. A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity. Antimicrob Agents Chemother. 2017;61(12):e01293-17. https://doi.org/10.1128/aac.01293-17
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