Monday, September 16, 2019

Short Summary of New Vancomycin Guideline Draft: Staying Up to Date with an Easy and Accurate Bayesian TDM Software


The current vancomycin guideline from 2009 recommends monitoring for vancomycin trough for nephrotoxicity in patients with high-dose vancomycin with trough between 15-20 mg/L, patients with concurrent nephrotoxins, patients with prolonged course of therapy, or renally unstable patients, and suggested to monitor AUC/MIC ≥400 mg*h/L for efficacy as a consensus among American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP).1 The upcoming newly revised vancomycin guideline currently being drafted recommends to target Bayesian-estimated AUC/MIC between 400 to 600 mg*h/L to maximize the efficacy and to minimize the likelihood of nephrotoxicity with consensus among ASHP, IDSA, SIDP, and Pediatric Infectious Diseases Society (PIDS).2
In the older guideline in 2009, the trough was used as a surrogate marker for AUC/MIC due to the difficulty of calculating AUC/MIC in real-time clinical practice.1,3  However, there are many studies that showed that trough value may not be the best target because trough targeting only ensures the efficacy, but not the safety. In the graph below, Pai et al. has shown that a wide range of vancomycin AUC can still have the same vancomycin trough, where trough target between 15-20 mg*h/L can have AUC values between 400 and 1750 mg*h/L.4 


 Pai et al 20144
One of the most concerning toxicity from overshooting vancomycin AUC is the vancomycin-associated acute kidney injury (AKI), which is defined as increase in SCr by ≥0.5 mg/dL, or 50% increase from baseline in consecutive daily readings, or 50% decrease in Creatinine Clearance (CrCL) in consecutive daily readings.1 Another vancomycin associated AKI is defined as SCr increase by ≥ 0.3 mg/dL in a 48-hour period.5–7 There was a significant association between AKI and vancomycin AUC between 600-800 mg*h/L compared to vancomycin AUC between 400-600 mg*h/L (P=0.014).8 Also, vancomycin AUC above 1300 mg*h/L was associated with 2.5 times the risk of AKI compared with those with vancomycin AUC below 1300 mg*h/L (P=0.02).9 Thus, the new guideline draft recommends Bayesian-guided vancomycin AUC/MIC ratio between 400 – 600 mg*h/L.2
Bayesian-guided dosing uses Bayes’ theorem with population PK parameter as Bayesian prior and uses patient’s observed serum concentrations to calculate the Bayesian posterior PK parameters. Bayesian dosing softwares can accurately estimate vancomycin AUC using limited sampling, as little as one trough level, and help achieve the target concentrations faster with less risk of nephrotoxicity.2 Now that the Bayesian dosing softwares are readily available, the new vancomycin guideline draft recommends monitoring AUC with Bayesian software programs embedded with richly sampled population PK model as the Bayesian prior.2

For medical doctors and clinical pharmacists to easily target Bayesian-estimated vancomycin AUC, PrecisePK (formerly known as T.D.M.S.) has been used in numerous hospitals world-wide for over 30 years. PrecisePK is an EHR integrated Therapeutic Drug Monitoring (TDM) Precision Dosing platform that is validated to give the most accurate and least biased vancomycin AUC results.10 As a leader in vancomycin AUC dosing, PrecisePK uses cutting-edge Machine Learning technology and Bayesian Analytics to individualize the vancomycin dosing for each patient. As a part of a bigger movement in precision medicine, PrecisePK brings artificial intelligence (A.I.) to individualized patient care and precision dosing. (Book a demo with us at: https://precisepk.com/live-demo/)
 













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References
1.         Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009;66(1):82-98. doi:10.2146/ajhp080434
2.         Rybak M, Le J, Lodise T, et al. Therapeutic Monitoring of Vancomycin: A revised consensus guideline and review of 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 (Draft). 2019:72.
3.         Liu C, Bayer A, Cosgrove SE, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children: Executive Summary. Clin Infect Dis. 2011;52(3):285-292. doi:10.1093/cid/cir034
4.         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. doi:10.1016/j.addr.2014.05.016
5.         Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31. doi:10.1186/cc5713
6.         Roy AK, Mc Gorrian C, Treacy C, et al. A Comparison of Traditional and Novel Definitions (RIFLE, AKIN, and KDIGO) of Acute Kidney Injury for the Prediction of Outcomes in Acute Decompensated Heart Failure. Cardiorenal Med. 2013;3(1):26-37. doi:10.1159/000347037
7.         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. doi:10.1128/AAC.01568-12
8.         Suzuki Y, Kawasaki K, Sato Y, et al. 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. doi:10.1159/000343162
9.         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. doi:10.1086/600884
10.       Turner RB, Kojiro K, Shephard EA, et al. Review and Validation of Bayesian Dose‐Optimizing Software and Equations for Calculation of the Vancomycin Area Under the Curve in Critically Ill Patients. Pharmacother J Hum Pharmacol Drug Ther. 2018;38(12):1174-1183. doi:10.1002/phar.2191

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