Skip to main content

Advertisement

SpringerLink
Log in

Population pharmacokinetics of vancomycin in patients with diabetic foot infection: a comparison of five models

  • Research article
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Purpose

This study aimed to compare individual pharmacokinetic (PK) parameters of vancomycin with predicted values from five population PK models in patients with diabetic foot infections (DFIs).

Methods

Patients with a diagnosis of DFI and an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min were included in the study. Individual PK data was carried on by collecting three vancomycin serum concentrations in a steady-state condition. Five published population-based nomograms were assumed to predict PK parameters. Optimal vancomycin exposure was considered as a trough level of 15–20 mg/L or the area under the curve over 24 h/minimum inhibitory concentration (AUC24/MIC) ≥ 400.

Results

A total of 48 samples from 16 patients were analyzed. There was a statistically significant difference between the volume of distribution (Vd) obtained from population methods and the individual estimations (P ≤ 0.001 in Ambrose and Burton, P = 0.010 and 0.006 in Bauer and Burton revised models, respectively). AUC/MIC ≥ 400 was achieved in 68.7% of patients while 50% had a trough level of less than 15 mg/L.

Conclusions

Vancomycin PK parameters, particularly individualized Vd, may not be predictable by population nomograms in patients with DFI and stable renal function. Moreover, the weak correlation between AUC24 values and trough concentrations underlines the starting practice of vancomycin AUC24-based monitoring and dosing in the clinical setting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data Availability

The authors confirm that the data supporting the findings of this study are available within the article.

References

  1. Lin S-Y, Lin N-Y, Huang Y-Y, Hsieh C-C, Huang Y-C. Methicillin-resistant Staphylococcus aureus nasal carriage and infection among patients with diabetic foot ulcer. J Microbiol Immunol Infect. 2020;53(2):292–9.

    Article  PubMed  Google Scholar 

  2. Henig O, Pogue JM, Martin E, Hayat U, Ja’ara M, Kilgore PE, Cha R, Dhar S, Kaye KS. The impact of multidrug-resistant organisms on outcomes in patients with diabetic foot infections. Open Forum Infect Dis. 2020;7(5):ofaa161). https://doi.org/10.1093/ofid/ofaa161

  3. Prompers L, Huijberts M, Schaper N, Apelqvist J, Bakker K, Edmonds M, et al. Resource utilisation and costs associated with the treatment of diabetic foot ulcers. Prospective data from the Eurodiale study. Diabetologia. 2008;51(10):1826–34.

    Article  CAS  PubMed  Google Scholar 

  4. Eleftheriadou I, Tentolouris N, Argiana V, Jude E, Boulton AJ. Methicillin-resistant Staphylococcus aureus in diabetic foot infections. Drugs. 2010;70(14):1785–97.

    Article  CAS  PubMed  Google Scholar 

  5. Elbarbry F. Vancomycin dosing and monitoring: critical evaluation of the current practice. Eur J Drug Metab Pharmacokinet. 2018;43(3):259–68.

    Article  CAS  PubMed  Google Scholar 

  6. Loc-Carrillo C, Wang C, Canden A, Burr M, Agarwal J. Local intramedullary delivery of vancomycin can prevent the development of long bone Staphylococcus aureus infection. PLoS One. 2016;11(7): e0160187.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Rodvold KA. 60 plus years later and we are still trying to learn how to dose vancomycin. Clin Infect Dis. 2020;70(8):1546–9.

  8. Hamada Y, Kuti JL, Nicolau DP. Vancomycin serum concentrations do not adequately predict tissue exposure in diabetic patients with mild to moderate limb infections. J Antimicrob Chemother. 2015;70(7):2064–7.

    Article  CAS  PubMed  Google Scholar 

  9. Burns AN, Goldman JL. A moving target—vancomycin therapeutic monitoring. J Pediatr Infect Dis Soc. 2020;9(4):474–8.

    Article  CAS  Google Scholar 

  10. Monteiro JF, Hahn SR, Gonçalves J, Fresco P. Vancomycin therapeutic drug monitoring and population pharmacokinetic models in special patient subpopulations. Pharmacol Res Perspect. 2018;6(4):e00420.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Marsot A, Boulamery A, Bruguerolle B, Simon N. Vancomycin. Clin Pharmacokinet. 2012;51(1):1–13.

  12. Chang C-H, Lin C-Y, Tian Y-C, Jenq C-C, Chang M-Y, Chen Y-C, et al. Acute kidney injury classification: comparison of AKIN and RIFLE criteria. Shock. 2010;33(3):247–52.

    Article  PubMed  Google Scholar 

  13. Bauer L. Vancomycin. Applied Clinical Pharmacokinetics, 2nd ed. McGraw Hill Medical; 2008. p. 207–98.

  14. Pai MP, Neely M, Rodvold KA, Lodise TP. Innovative approaches to optimizing the delivery of vancomycin in individual patients. Adv Drug Deliv Rev. 2014;77:50–7.

    Article  CAS  PubMed  Google Scholar 

  15. Cockcroft DW, Gault H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41.

    Article  CAS  PubMed  Google Scholar 

  16. Murphy JE, Gillespie DE, Bateman CV. Predictability of vancomycin trough concentrations using seven approaches for estimating pharmacokinetic parameters. Am J Health Syst Pharm. 2006;63(23):2365–70.

    Article  CAS  PubMed  Google Scholar 

  17. Matzke GR, Mcgory RW, Halstenson CE, Keane WF. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrob Agents Chemother. 1984;25(4):433–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bauer L. Carbamazepine. Applied Clinical Pharmacokinetics. 2nd ed. New York: McGraw-Hill Education; 2008. p. 548–62.

  19. Winter ME, Katcher BS, Koda-Kimble MA. Basic clinical pharmacokinetics. Philadelphia: Lippincott Williams & Wilkins; 2004.

  20. Burton ME, Gentle DL, Vasko MR. Evaluation of a Bayesian method for predicting vancomycin dosing. DICP. 1989;23(4):294–300. https://doi.org/10.1177/106002808902300404

  21. Giuliano C, Haase KK, Hall R. Use of vancomycin pharmacokinetic–pharmacodynamic properties in the treatment of MRSA infections. Expert Rev Anti Infect Ther. 2010;8(1):95–106.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Abraham J, Sinnollareddy MG, Roberts MS, Williams P, Peake SL, Lipman J, et al. Plasma and interstitial fluid population pharmacokinetics of vancomycin in critically ill patients with sepsis. Int J Antimicrob Agents. 2019;53(2):137–42.

    Article  CAS  PubMed  Google Scholar 

  23. Heffernan A, Germano A, Sime F, Roberts JA, Kimura E. Vancomycin population pharmacokinetics for adult patients with sepsis or septic shock: are current dosing regimens sufficient? Eur J Clin Pharmacol. 2019;75(9):1219–26.

    Article  CAS  PubMed  Google Scholar 

  24. Rybak MJ, Le J, Lodise TP, Levine DP, Bradley JS, Liu C, et al. 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. Clin Infect Dis. 2020;71(6):1361–4.

    Article  CAS  PubMed  Google Scholar 

  25. Meng L, Wong T, Huang S, Mui E, Nguyen V, Espinosa G, et al. Conversion from vancomycin trough concentration–guided dosing to area under the curve–guided dosing using two sample measurements in adults: implementation at an academic medical center. Pharmacotherapy. 2019;39(4):433–42.

    Article  CAS  PubMed  Google Scholar 

  26. Drennan PG, Begg EJ, Gardiner SJ, Kirkpatrick CM, Chambers ST. The dosing and monitoring of vancomycin: what is the best way forward? Int J Antimicrob Agents. 2019;53(4):401–7.

    Article  CAS  PubMed  Google Scholar 

  27. Chu Y, Luo Y, Qu L, Zhao C, Jiang M. Application of vancomycin in patients with varying renal function, especially those with augmented renal clearance. Pharm Biol. 2016;54(12):2802–6.

    Article  CAS  PubMed  Google Scholar 

  28. Mogle BT, Steele JM, Seabury RW, Dang UJ, Kufel WD. Implementation of a two-point pharmacokinetic AUC-based vancomycin therapeutic drug monitoring approach in patients with methicillin-resistant Staphylococcus aureus bacteraemia. Int J Antimicrob Agents. 2018;52(6):805–10.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We express our sincere gratitude towards the endocrinology department team at Shariati Hospital for their cooperation in this study.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacy, International Campus, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Hedieh Tazerouni

  2. Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran

    Hedieh Tazerouni, Kheirollah Gholami & Kourosh Sadeghi

  3. Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Zohre Labbani-Motlagh, Shahideh Amini, Bita Shahrami, Kheirollah Gholami & Kourosh Sadeghi

  4. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Sayed Mahmoud Sajjadi-Jazi

  5. Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Sayed Mahmoud Sajjadi-Jazi

  6. Department of Infectious Disease, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Shirin Afhami

Authors
  1. Hedieh Tazerouni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zohre Labbani-Motlagh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shahideh Amini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bita Shahrami
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sayed Mahmoud Sajjadi-Jazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shirin Afhami
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kheirollah Gholami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kourosh Sadeghi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kourosh Sadeghi.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to declare.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tazerouni, H., Labbani-Motlagh, Z., Amini, S. et al. Population pharmacokinetics of vancomycin in patients with diabetic foot infection: a comparison of five models. J Diabetes Metab Disord 22, 1385–1390 (2023). https://doi.org/10.1007/s40200-023-01259-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-023-01259-5

Keywords

Search

Navigation