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/)
#precisiondosing
#precisionmedicine
#pharmacokinetics
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#vancomycin
#vancomycindosing
#vancomycinauc
#vancomycinaucdosing
#TDM
#therapeuticdrugmonitoring
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#NewVancomycinGuideline
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
