Skip to main content

Advertisement

SpringerLink
Log in

Design and prospective validation of a dosing instrument for continuous infusion of vancomycin: a within-population approach

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Introduction

The clinical application of continuous infusion (CoI) of vancomycin has gained interest in recent years. Since no international guidelines on initial dosing of vancomycin CoI exist, there is a need for methods to facilitate the switch from intermittent to continuous vancomycin dosing algorithms in clinically infected populations. Therefore, the aim of this study was to design and validate an a priori dosing schedule for CoI of vancomycin in clinical practice.

Methods

A dosing table for CoI of vancomycin based on estimated glomerular filtration rate (eGFR) was developed by simulation of continuous infusion of vancomycin using pharmacokinetic (PK) software and a PK population model designed from historical within-population data in intermittently dosed patients. The target range for the first vancomycin serum concentrations drawn approximately 24 h after start of infusion’ (C24) was set at 15–20 mg/L corresponding with an area under the curve (AUC) of at least 350 mg·h·L−1. The performance of the dosing schedule was primarily assessed by describing the percentages of patients attaining the predefined target.

Results

An eGFR-derived dosing schedule for CoI of vancomycin was established and implemented in clinical practice. Prospective assessment in 35 general ward and 45 intensive care unit patients showed that the C24 target was reached in 69 and 63 % and the AUC target was attained in 80 and 72 % of patients, respectively.

Conclusions

An easy method to design and validate an eGFR-derived dosing algorithm for the continuous infusion of vancomycin to switch from intermittent to continuous dosing of vancomycin was developed.

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

References

  1. Moise-Broder PA, Forrest A, Birmingham MC, Schentag JJ (2004) Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet 43:925–942

    Article  PubMed  CAS  Google Scholar 

  2. Rybak MJ (2006) The pharmacokinetic and pharmacodynamic properties of vancomycin. Clin Infect Dis 42(Suppl 1):S35–39

    Article  PubMed  CAS  Google Scholar 

  3. Tenover FC, Biddle JW, Lancaster MV (2001) Increasing resistance to vancomycin and other glycopeptides in Staphylococcus aureus. Emerg Infect Dis 7:327–332

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, Ryback JM, Talan DA, Chambers HF (2011) Clinical practice guidelines by the clinically infected diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis 52:285–292

    Article  PubMed  Google Scholar 

  5. Rybak M, Lomaestro B, Rotschafer JC, Moellering R Jr, Craig W, Billeter M, Dalovisio JR, Levine DP (2009) Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American society of health-system pharmacists, the clinically infected diseases society of America, and the society of clinically infected diseases pharmacists. Am J Health Syst Pharm 66:82–98

    Article  PubMed  CAS  Google Scholar 

  6. Hidayat LK, Hsu DI, Quist R, Shriner KA, Wong-Beringer A (2006) High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. Arch Intern Med 166:2138–2144

    Article  PubMed  Google Scholar 

  7. Pea F, Viale P (2007) Pharmacodynamics of antibiotics to treat multidrug-resistant Gram-positive hospital infections. Expert Rev Anti Infect Ther 5:255–270

    Article  PubMed  CAS  Google Scholar 

  8. Rybak MJ, Lomaestro BM, Rotschafer JC, Moellering RC, Craig WA, Billeter M, Dalovisio JR, Levine DP (2009) Vancomycin therapeutic guidelines: a summary of consensus recommendations from the clinically infected diseases society of America, the American society of health-system pharmacists, and the society of clinically infected diseases pharmacists. Clin Infect Dis 49:325–327

    Article  PubMed  Google Scholar 

  9. Cataldo MA, Tacconelli E, Grilli E, Pea F, Petrosillo N (2012) Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis. J Antimicrob Chemother 67:17–24

    Article  PubMed  CAS  Google Scholar 

  10. van Maarseveen EM, Man WH, Touw DJ, Bouma AW, van Zanten AR (2011) Continuous and intermittent infusion of vancomycin equally effective: review of the literature. Ned Tijdschr Geneeskd 155:A2667

    PubMed  Google Scholar 

  11. Schmelzer, T.M., A.B... Christmas, H.J. Norton, B.T. Heniford and R.F. Sing Vancomycin intermittent dosing versus continuous infusion for treatment of ventilator-associated pneumonia in trauma patients, Am Surg 79: 1185–1190

  12. Raverdy, V., E. Ampe, J.D. Hecq and P.M. Tulkens stability and compatibility of vancomycin for administration by continuous infusion, J Antimicrob Chemother 68: 1179–1182

  13. Bernard L, El H, Pron B, Lotthe A, Gleizes V, Signoret F, Denormandie P, Gaillard JL, Perronne C (2001) Outpatient parenteral antimicrobial therapy (OPAT) for the treatment of osteomyelitis: evaluation of efficacy, tolerance and cost. J Clin Pharm Ther 26:445–451

    Article  PubMed  CAS  Google Scholar 

  14. van Zanten AR, Engelfriet PM, van Dillen K, van Veen M, Nuijten MJ, Polderman KH (2003) Importance of nondrug costs of intravenous antibiotic therapy. Crit Care 7:R184–190

    Article  PubMed  PubMed Central  Google Scholar 

  15. Boffi El Amari E, Vuagnat A, Stern R, Assal M, Denormandie P, Hoffmeyer P, Bernard L (2004) High versus standard dose vancomycin for osteomyelitis. Scand J Infect Dis 36:712–717

    PubMed  CAS  Google Scholar 

  16. Hutschala D, Kinstner C, Skhirdladze K, Thalhammer F, Muller M, Tschernko E (2009) Influence of vancomycin on renal function in critically ill patients after cardiac surgery: continuous versus intermittent infusion. Anesthesiology 111:356–365

    Article  PubMed  CAS  Google Scholar 

  17. Pea F, Furlanut M, Negri C, Pavan F, Crapis M, Cristini F, Viale P (2009) Prospectively validated dosing nomograms for maximizing the pharmacodynamics of vancomycin administered by continuous infusion in critically ill patients. Antimicrob Agents Chemother 53:1863–1867

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Vuagnat A, Stern R, Lotthe A, Schuhmacher H, Duong M, Hoffmeyer P, Bernard L (2004) High dose vancomycin for osteomyelitis: continuous vs. intermittent infusion. J Clin Pharm Ther 29:351–357

    Article  PubMed  CAS  Google Scholar 

  19. Wysocki M, Delatour F, Faurisson F, Rauss A, Pean Y, Misset B, Thomas F, Timsit JF, Similowski T, Mentec H, Mier L, Dreyfuss D (2001) Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomized study. Antimicrob Agents Chemother 45:2460–2467

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Ingram PR, Lye DC, Fisher DA, Goh WP, Tam VH (2009) Nephrotoxicity of continuous versus intermittent infusion of vancomycin in outpatient parenteral antimicrobial therapy. Int J Antimicrob Agents 34:570–574

    Article  PubMed  CAS  Google Scholar 

  21. Spapen HD, Janssen van Doorn K, Diltoer M, Verbrugghe W, Jacobs R, Dobbeleir N, Honore PM, Jorens PG (2011) Retrospective evaluation of possible renal toxicity associated with continuous infusion of vancomycin in critically ill patients. Ann Intensive Care 1:26

    Article  PubMed  PubMed Central  Google Scholar 

  22. Bosso JA, Nappi J, Rudisill C, Wellein M, Bookstaver PB, Swindler J, Mauldin PD (2011) Relationship between vancomycin trough concentrations and nephrotoxicity: a prospective multicenter trial. Antimicrob Agents Chemother 55:5475–5479

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Elyasi S, Khalili H, Dashti-Khavidaki S, Mohammadpour A (2012) Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations. A literature review. Eur J Clin Pharmacol 68:1243–1255

    Article  PubMed  CAS  Google Scholar 

  24. Proost JH, Meijer DK (1992) MW/Pharm, an integrated software package for drug dosage regimen calculation and therapeutic drug monitoring. Comput Biol Med 22:155–163

    Article  PubMed  CAS  Google Scholar 

  25. Pullen J, de Rozario L, Stolk LM, Degraeuwe PL, van Tiel FH, Zimmermann LJ (2006) Population pharmacokinetics and dosing of flucloxacillin in preterm and term neonates. Ther Drug Monit 28:351–358

    Article  PubMed  CAS  Google Scholar 

  26. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med 130:461–470

    Article  PubMed  CAS  Google Scholar 

  27. Kullar R, Davis SL, Taylor TN, Kaye KS, Rybak MJ (2012) Effects of targeting higher vancomycin trough levels on clinical outcomes and costs in a matched patient cohort. Pharmacotherapy 32:195–201

    Article  PubMed  Google Scholar 

  28. Roberts JA, Taccone FS, Udy AA, Vincent JL, Jacobs F, Lipman J (2011) Vancomycin dosing in critically ill patients: robust methods for improved continuous-infusion regimens. Antimicrob Agents Chemother 55:2704–2709

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Pea F, Furlanut M, Negri C, Pavan F, Crapis M, Cristini F, Viale P (2009) Prospectively validated dosing nomograms for maximizing the pharmacodynamics of vancomycin administered by continuous infusion in critically ill patients. Antimicrob Agents Chemother 53:1863–1867

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  30. Baptista JP, Udy AA, Sousa E, Pimentel J, Wang L, Roberts JA, Lipman J (2011) A comparison of estimates of glomerular filtration in critically ill patients with augmented renal clearance. Crit Care 15:R139

    Article  PubMed  PubMed Central  Google Scholar 

  31. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612

    Article  PubMed  PubMed Central  Google Scholar 

  32. Accetta NA, Gladstone EH, DiSogra C, Wright EC, Briggs M, Narva AS (2008) Prevalence of estimated GFR reporting among US clinical laboratories. Am J Kidney Dis 52:778–787

    Article  PubMed  PubMed Central  Google Scholar 

  33. Imbasciati, E., R. Falbo, P. Mariani, S. Signorelli, A. Stella and P. Brambilla (2012) A regional survey of serum creatinine measurement methods and estimated glomerular filtration rate reporting, J Nephrol: 0

  34. Rodvold KA, Blum RA, Fischer JH, Zokufa HZ, Rotschafer JC, Crossley KB, Riff LJ (1988) Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrob Agents Chemother 32:848–852

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. De Waele, J.J., I. Danneels, P. Depuydt, J. Decruyenaere, M. Bourgeois and E. Hoste Factors associated with inadequate early vancomycin levels in critically ill patients treated with continuous infusion, Int J Antimicrob Agents 41: 434–438

  36. Saugel, B., M.C. Nowack, A. Hapfelmeier, A. Umgelter, C. Schultheiss, P. Thies, V. Phillip, F. Eyer, R.M. Schmid and W. Huber Continuous intravenous administration of vancomycin in medical intensive care unit patients, J Crit Care 28: 9–13

  37. Ocampos-Martinez E, Penaccini L, Scolletta S, Abdelhadii A, Devigili A, Cianferoni S, de Backer D, Jacobs F, Cotton F, Vincent JL, Taccone FS (2012) Determinants of early inadequate vancomycin concentrations during continuous infusion in septic patients. Int J Antimicrob Agents 39:332–337

    Article  PubMed  CAS  Google Scholar 

  38. Chen, Y.C., J.F. Feng, B. Li, L. Zhang and Y.W. Yang Estimation of safe and effective dose of vancomycin in MRSA-infected patients using serum cystatin C concentrations, Int J Clin Pharmacol Ther 51: 161–169

Download references

Funding

This work was not supported by outside funding. All work was funded by our department research budget.

Transparency declarations

None of the authors has conflicts of interest to declare.

Author information

Author notes

  1. Daniel J. Touw

    Present address: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands

Authors and Affiliations

  1. Department of Clinical Pharmacy, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Erik M. van Maarseveen

  2. Department of Clinical Pharmacy, Groene Hart Ziekenhuis, Beulandweg 10, 2803 HH, Gouda, The Netherlands

    Annemien Bouma

  3. Department of Clinical Pharmacy, Haga Teaching Hospital, Leyweg 275, 2545 CH, The Hague, The Netherlands

    Daniel J. Touw

  4. Department of Clinical Pharmacy, Central Pharmacy The Hague, Escamplaan 900, 2547 EX, The Hague, The Netherlands

    Daniel J. Touw

  5. Department of Clinical Pharmacy and CAPHRI, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands

    Cees Neef

  6. Department of Intensive Care, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716 RP, Ede, The Netherlands

    Arthur R. H. van Zanten

Authors
  1. Erik M. van Maarseveen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annemien Bouma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel J. Touw
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cees Neef
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arthur R. H. van Zanten
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erik M. van Maarseveen.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 41.5 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

van Maarseveen, E.M., Bouma, A., Touw, D.J. et al. Design and prospective validation of a dosing instrument for continuous infusion of vancomycin: a within-population approach. Eur J Clin Pharmacol 70, 1353–1359 (2014). https://doi.org/10.1007/s00228-014-1742-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-014-1742-6

Keywords

Search

Navigation