Abstract
Purpose
Vancomycin (VCM) concentration is often out of therapeutic range (10–20 μg/ml) in patients receiving continuous renal replacement therapy (CRRT). The purposes of this study were to develop a practical VCM population pharmacokinetic (PPK) model and to evaluate the potential of Bayesian prediction-based therapeutic drug monitoring (Bayes-TDM) in VCM dose individualization for patients receiving CRRT.
Methods
We developed a VCM PPK model using 80 therapeutic concentrations in 17 patients receiving CRRT. Bayes-TDM with the VCM PPK model was evaluated in 23 patients after PPK modeling.
Results
We identified the covariates reduced urine output (RUO, <0.5 ml/kg/h) and effluent flow rate of CRRT for the VCM PPK model. The mean VCM non CRRT clearance (CLnonCRRT) was 2.12 l/h. RUO lowered CLnonCRRT to 0.34 l/h. The volume of distribution was 91.3 l/70 kg. The target concentration attainment rate by Bayes-TDM was higher (87.0%) than that by the PPK modeling period (53.8%, P = 0.046). The variance of the second measured concentrations by the Bayes-TDM was lower (11.5, standard deviation: 3.4 μg/ml) than that by the PPK modeling period (50.5, standard deviation: 7.1 μg/ml, P = 0.003).
Conclusions
Bayes-TDM could be a useful tool for VCM dose individualization in patients receiving CRRT.
Similar content being viewed by others
Abbreviations
- 95% CI:
-
95% Confidence interval
- AKI:
-
Acute kidney injury
- AUC:
-
Area under concentration curve
- AUC0–24/MIC:
-
Area under concentration curve divided by minimum inhibitory concentration
- Bayes-TDM:
-
Bayesian prediction based therapeutic drug monitoring
- CLCRRT :
-
Clearance by continuous renal replacement therapy
- CLnonCRRT :
-
Clearance by non continuous renal replacement therapy
- COV:
-
Covariate
- CRRT:
-
Continuous renal replacement therapy
- CWRES:
-
Conditional weighted residuals
- IIV:
-
Inter-individual variability
- KDIGO:
-
Kidney disease improving global outcomes
- MIC:
-
Minimum inhibitory concentration
- MRSA:
-
Methicillin-resistant Staphylococcus aureus
- NONMEM:
-
Non linear mixed effect modeling
- OFV:
-
Objective function value
- pcVPC:
-
Prediction corrected visual predictive check
- PPK:
-
Population pharmacokinetic(s)
- RMSPE:
-
Root mean square percentage error
- RUO:
-
Patients with RUO
- RUO-:
-
Patients without RUO
- RUO:
-
Reduced urine output
- SD:
-
Standard deviation
- SOFA:
-
Sequential organ failure assessment
- TA:
-
Target concentration range attainment rate
- TDM:
-
Therapeutic drug monitoring
- VBA:
-
Visual basic for applications
- VCM:
-
Vancomycin
- Vdss:
-
Volume of distribution including central and peripheral volumes
References
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315:801–10.
Clark WR, Neri M, Garzotto F, Ricci Z, Goldstein SL, Ding X, et al. The future of critical care: renal support in 2027. Crit Care. 2017;21:92.
Passos RD, Ramos JG, Gobatto A, Mendonça EJ, Miranda EA, Dutra FR, et al. Lactate clearance is associated with mortality in septic patients with acute kidney injury requiring continuous renal replacement therapy: a cohort study. Medicine (Baltimore). 2016;95:e5112.
Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589–96.
Matzke GR, Aronoff GR, Atkinson AJ Jr, Bennett WM, Decker BS, Eckardt KU, et al. Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from kidney disease: improving global outcomes (KDIGO). Kidney Int. 2011;80:1122–37.
Kielstein JT, David S. Pro: Renal replacement trauma or Paracelsus 2.0. Nephrol Dial Transplant. 2013;28:2728–31.
Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, 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. Clin Infect Dis. 2011;52:e18–55.
Matzke GR, Zhanel GG, Guay DR. Clinical pharmacokinetics of vancomycin. Clin Pharmacokinet. 1986;11:257–82.
Matsumoto K, Takesue Y, Ohmagari N, Mochizuki T, Mikamo H, Seki M, et al. Practice guidelines for therapeutic drug monitoring of vancomycin: a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring. J Infect Chemother. 2013;19:365–80.
Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, 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;66:82–98.
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;49:507–14.
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;57:734–44.
Men P, Li HB, Zhai SD, Zhao RS. Association between the AUC0-24/MIC ratio of vancomycin and its clinical effectiveness: a systematic review and meta-analysis. PLoS One. 2016;11:e0146224.
Kees MG, Wicha SG, Seefeld A, Kees F, Kloft C. Unbound fraction of vancomycin in intensive care unit patients. J Clin Pharmacol. 2014;54:318–23.
Blot S, Koulenti D, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, et al. Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study Crit Care. 2014;18:R99.
Ulldemolins M, Rello J. The relevance of drug volume of distribution in antibiotic dosing. Curr Pharm Biotechnol. 2011;12:1996–2001.
Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2010;49:1–16.
Sheiner LB, Rosenberg B, Marathem VV. Forecasting individual pharmacokinetics. Clin Pharmacol Ther. 1979;26:294–305.
Oda K, Kasada T, Yoshikawa M, Tanoue M, Yamashita T, Takeshita Y. Therapeutic drug monitoring based on early measurements of serum teicoplanin levels in Japanese patients. Ther Drug Monit. 2014;36:401–5.
Yasuhara M, Iga T, Zenda H, Okumura K, Oguma T, Yano Y, et al. Population pharmacokinetics of vancomycin in Japanese adult patients. Ther Drug Monit. 1998;20:139–48.
DelDot ME, Lipman J, Tett SE. Vancomycin pharmacokinetics in critically ill patients receiving continuous venovenous haemodiafiltration. Br J Clin Pharmacol. 2004;58:259–68.
Boereboom FTJ, Ververs FFT, Blankestijn PJ, Savelkoul TJF, van Dijk A. Vancomycin clearance during continuous venovenous haemofiltration in critically ill patients. Intensive Care Med. 1999;25:1100–4.
Santré C, Leroy O, Simon M, Georges H, Guery B, Beuscart C, et al. Pharmacokinetics of vancomycin during continuous hemodiafiltration. Intensive Care Med. 1993;19:347–50.
Roberts DM, Liu X, Roberts JA, Nair P, Cole L, Roberts MS, et al. A multicenter study on the effect of continuous hemodiafiltration intensity on antibiotic pharmacokinetics. Crit Care. 2015;19:84.
Udy AA, Covajes C, Taccone FS, Jacobs F, Vincent JL, Lipman J, et al. Can population pharmacokinetic modelling guide vancomycin dosing during continuous renal replacement therapy in critically ill patients? Int J Antimicrob Agents. 2013;41:564–8.
Vincent JL, de Mendonca A, Cantraine F. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Crit Care Med. 1998;26:1793–800.
Yamamoto T, Yasuno N, Kadata S, Hisaka A, Hanafusa N, Noiri E, et al. Proposal of a pharmacokinetically optimized dosage regimen of antibiotics in patients receiving continuous hemodiafiltration. Antimicrob Agents Chemother. 2011;55:5804–12.
Reetze-Bonorden P, Böhler J, Keller E. Drug dosage in patients during continuous renal replacement therapy. Pharmacokinetic and therapeutic considerations. Clin Pharmacokinet. 1993;24:362–79.
Trotman RL, Williamson JC, Shoemaker DM, Salzer WL. Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy. Clin Infect Dis. 2005;41:1159–66.
Lindbom L, Ribbing J, Jonsson EN. Perl-speaks-NONMEM (PsN)--a Perl module for NONMEM related programming. Comput Methods Prog Biomed. 2004;75:85–94.
Colin PJ, Allegaert K, Thomson AH, Touw DJ, Dolton M, de Hoog M, et al. Vancomycin pharmacokinetics throughout life: results from a pooled population analysis and evaluation of current dosing recommendations. Clin Pharmacokinet. 2019;58:767–80.
Neely MN, Youn G, Jones B, Jelliffe RW, Drusano GL, Rodvold KA, et al. Are vancomycin trough concentrations adequate for optimal dosing? Antimicrob Agents Chemother. 2014;58:309–16.
Bel Kamel A, Bourguignon L, Marcos M, Ducher M, Goutelle S. Is trough concentration of vancomycin predictive of the area under the curve? A clinical study in elderly patients. Ther Drug Monit. 2017;39:83–7.
Kidney disease Improving Global Outcomes. KDIGO clinical practice guideline for acute kidney injury. Kidney Int. 2012;Suppl 2:1–138.
Berthoin K, Ampe E, Tulkens PM, Carryn S. Correlation between free and total vancomycin serum concentrations in patients treated for gram-positive infections. Int J Antimicrob Agents. 2009;34:555–60.
Jamal JA, Udy AA, Lipman J, Roberts JA. The impact of variation in renal replacement therapy settings on piperacillin, meropenem, and vancomycin drug clearance in the critically ill: an analysis of published literature and dosing regimens. Crit Care Med. 2014;42:1640–50.
Broeker A, Nardecchia M, Klinker KP, Derendorf H, Day RO, Marriott DJ, Carland JE, Stocker SL, Wicha SG. Towards precision dosing of vancomycin: a systematic evaluation of pharmacometric models for Bayesian forecasting. Clin Microbiol Infect. 2019;25:1286.e1–1286.e7.
Colin PJ, Jonckheere S, Struys MMRF. Target-controlled continuous infusion for antibiotic dosing: proof-of-principle in an in-silico Vancomycin trial in intensive care unit patients. Clin Pharmacokinet. 2018;57:1435–47.
Zelenitsky S, Rubinstein E, Ariano R, Iacovides H, Dodek P, Mirzanejad Y, et al. Cooperative Antimicrobial Therapy of Septic Shock-CATSS Database Research Group Vancomycin pharmacodynamics and survival in patients with methicillin-resistant Staphylococcus aureus-associated septic shock. Int J Antimicrob Agents. 2013;41:255–60.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 168 kb)
Rights and permissions
About this article
Cite this article
Oda, K., Jono, H., Kamohara, H. et al. Development of Vancomycin Dose Individualization Strategy by Bayesian Prediction in Patients Receiving Continuous Renal Replacement Therapy. Pharm Res 37, 108 (2020). https://doi.org/10.1007/s11095-020-02820-0
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11095-020-02820-0