Ann Lab Med.  2025 Jan;45(1):85-89. 10.3343/alm.2024.0218.

Interinstitutional Comparison of Vancomycin Area Under the Concentration–Time Curve Estimation in Korea: Need for Standardized Operational Protocols for Therapeutic Drug Monitoring Consultation

• Kim HK
• Park M
• Seo JD
• Jeong TD
• Ji M

• KMID: 2563859
• DOI: http://doi.org/10.3343/alm.2024.0218

Abstract

Vancomycin, a vital antibiotic for treating gram-positive bacterial infections, requires therapeutic drug monitoring (TDM) because of its substantial pharmacokinetic variability. While traditional TDM relies on steady-state trough concentrations, recent guidelines advocate the area under the concentration–time curve (AUC) as the target index. However, detailed protocols for AUC estimation are lacking, leading to potential discrepancies among institutions. We surveyed medical institutions in Korea regarding vancomycin TDM, including AUC estimation. Nineteen participants responded to the TDM case challenge under three patient scenarios. For an ordinary patient in Case 1, the overall CV for AUC values was 0.4% when both trough and peak concentrations were included in the AUC calculation and 1.9% when utilizing only the trough concentration. For Case 2, an older patient with obesity, the corresponding CV was 6.6%. For Case 3 with multiple trough concentrations, the CV was 15.6%, reflecting variations in the selective use of data. Although the agreements in Case 1 were good, significant variability in AUC estimation was noted in cases involving atypical patient characteristics or old TDM data. Our study provides insight into the current status of vancomycin TDM in Korea and underscores the need for standardized operational protocols for AUC estimation.

Keyword

Area under the concentration–time curve; Therapeutic drug monitoring; Vancomycin

Figure

• 

  Fig. 1 Boxplot showing the distribution of the reported AUC24 values. Each data point represents a value reported by an institution. The data points are shaped according to the Bayesian program used for the calculation. Abbreviations: AUC24, 24 hr-normalized area under the concentration–time curve; CAPCIL, continuous assessment of pharmaceutical care to improve life; PKS, abbottbase pharmacokinetic system.

Reference

References

1. Monteiro JF, Hahn SR, Gonçalves J, Fresco P. 2018; Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations. Pharmacol Res Perspect. 6:e00420. DOI: 10.1002/prp2.420. PMID: 30156005. PMCID: PMC6113434.

2. Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr., Craig W, Billeter M, et al. 2009; 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. 66:82–98. DOI: 10.2146/ajhp080434. PMID: 19106348.

3. Rybak MJ, Le J, Lodise TP, Levine DP, Bradley JS, Liu C, et al. 2020; 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. 77:835–64. DOI: 10.1093/ajhp/zxaa036. PMID: 32191793.

4. Matsumoto K, Oda K, Shoji K, Hanai Y, Takahashi Y, Fujii S, et al. 2022; Clinical practice guidelines for therapeutic drug monitoring of vancomycin in the framework of model-informed precision dosing: a consensus review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring. Pharmaceutics. 14:DOI: 10.3390/pharmaceutics14030489. PMID: 35335866. PMCID: PMC8955715. PMID: 9a2a82f4726e4a3891448d6136c9d0ac.

5. Oda K, Hashiguchi Y, Kimura T, Tsuji Y, Shoji K, Takahashi Y, et al. 2021; Performance of area under the concentration-time curve estimations of vancomycin with limited sampling by a newly developed web application. Pharm Res. 38:637–46. DOI: 10.1007/s11095-021-03030-y. PMID: 33782837.

6. Turner RB, Kojiro K, Shephard EA, Won R, Chang E, Chan D, et al. 2018; Review and validation of Bayesian dose-optimizing software and equations for calculation of the vancomycin area under the curve in critically ill patients. Pharmacotherapy. 38:1174–83. DOI: 10.1002/phar.2191. PMID: 30362592.

7. Kim HK, Jeong TD. 2023; Evaluation of vancomycin area under the concentration-time curve predictive performance using Bayesian modeling software with and without peak concentration: an academic hospital experience for adult patients without renal impairment. Ann Lab Med. 43:554–64. DOI: 10.3343/alm.2023.43.6.554. PMID: 37387488. PMCID: PMC10345177.

8. Aljutayli A, Thirion DJG, Bonnefois G, Nekka F. 2022; Pharmacokinetic equations versus Bayesian guided vancomycin monitoring: pharmacokinetic model and model-informed precision dosing trial simulations. Clin Transl Sci. 15:942–53. DOI: 10.1111/cts.13210. PMID: 35170243. PMCID: PMC9010252. PMID: 97bb6b8a51794810a200517ebbea8b2c.

9. Kim B, Hwang S, Heo E, Kim HS, Jung J, Kim ES, et al. 2023; Evaluation of vancomycin TDM strategies: prediction and prevention of kidney injuries based on vancomycin TDM results. J Korean Med Sci. 38:e101. DOI: 10.3346/jkms.2023.38.e101. PMID: 37038640. PMCID: PMC10086380.

10. Lee BV, Fong G, Bolaris M, Neely M, Minejima E, Kang A, et al. 2021; Cost-benefit analysis comparing trough, two-level AUC and Bayesian AUC dosing for vancomycin. Clin Microbiol Infect. 27:1346.e1–e7. DOI: 10.1016/j.cmi.2020.11.008. PMID: 33221430.

11. Neely MN, Youn G, Jones B, Jelliffe RW, Drusano GL, Rodvold KA, et al. 2014; Are vancomycin trough concentrations adequate for optimal dosing? Antimicrob Agents Chemother. 58:309–16. DOI: 10.1128/AAC.01653-13. PMID: 24165176. PMCID: PMC3910745.

12. Neef C, Touw DJ, Harteveld AR, Eerland JJ, Uges DR. 2006; Pitfalls in TDM of antibiotic drugs: analytical and modelling issues. Ther Drug Monit. 28:686–9. DOI: 10.1097/01.ftd.0000243966.97964.11. PMID: 17038886.

13. Glatard A, Bourguignon L, Jelliffe RW, Maire P, Neely MN, Goutelle S. 2015; Influence of renal function estimation on pharmacokinetic modeling of vancomycin in elderly patients. Antimicrob Agents Chemother. 59:2986–94. DOI: 10.1128/AAC.04132-14. PMID: 25753640. PMCID: PMC4432143.

14. Kim HK, Jeong TD. 2023; Clinical relevance of a vancomycin 24 h area under the concentration-time curve values using different renal function equations in Bayesian dosing software. J Pers Med. 13:120. DOI: 10.3390/jpm13010120. PMID: 36675782. PMCID: PMC9862358.

15. Winter MA, Guhr KN, Berg GM. 2012; Impact of various body weights and serum creatinine concentrations on the bias and accuracy of the Cockcroft-Gault equation. Pharmacotherapy. 32:604–12. DOI: 10.1002/j.1875-9114.2012.01098.x. PMID: 22576791.

16. Spruill WJ, Wade WE, Cobb HH 3rd. 2007; Estimating glomerular filtration rate with a modification of diet in renal disease equation: implications for pharmacy. Am J Health Syst Pharm. 64:652–60. DOI: 10.2146/ajhp060239. PMID: 17353576.

17. Broeker A, Nardecchia M, Klinker KP, Derendorf H, Day RO, Marriott DJ, et al. 2019; Towards precision dosing of vancomycin: a systematic evaluation of pharmacometric models for Bayesian forecasting. Clin Microbiol Infect. 25:1286.e1–e7. DOI: 10.1016/j.cmi.2019.02.029. PMID: 30872102.

18. Guo T, van Hest RM, Zwep LB, Roggeveen LF, Fleuren LM, Bosman RJ, et al. 2020; Optimizing Predictive Performance of Bayesian Forecasting for Vancomycin Concentration in Intensive Care Patients. Pharm Res. 37:171. DOI: 10.1007/s11095-020-02908-7. PMID: 32830297. PMCID: PMC7443423.

19. Reuter SE, Stocker SL, Alffenaar JC, Baldelli S, Cattaneo D, Jones G, et al. 2022; Optimal practice for vancomycin therapeutic drug monitoring: position statement from the Anti-Infectives Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. Ther Drug Monit. 44:121–32. DOI: 10.1097/FTD.0000000000000944. PMID: 34882107.

20. Choi R, Woo HI, Park HD, Lee SY. 2019; A nationwide utilization survey of therapeutic drug monitoring for five antibiotics in South Korea. Infect Drug Resist. 12:2163–73. DOI: 10.2147/IDR.S208783. PMID: 31410036. PMCID: PMC6646174.