Skip to main content
SpringerLink
Log in

Pharmacokinetic/pharmacodynamic analysis of vancomycin in ICU patients

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Aims

To identify the variables affecting vancomycin pharmacokinetics in medical ICU patients and to evaluate the potential efficacy of dosage schedules by PK/PD analysis.

Design

A retrospective pharmacokinetic analysis of serum levels obtained in routine vancomycin monitoring was performed.

Setting

A 12-bed general ICU of a university teaching hospital.

Patients

Forty-six vancomycin-treated ICU patients fitting the following criteria: over 18 years old; more than three concentration data per patient; absence of renal replacement support, cardiac surgery and neoplastic disorders.

Interventions

Clinical information was collected from the patients' medical records. Details of vancomycin therapy, dosage and blood sampling times were obtained from pharmacokinetic reports. Population analysis were made by the standard two-stage approach.

Measurements and main results

Vancomycin clearance and distribution volume were estimated individually assuming a one-compartment pharmacokinetic model. PK/PD analysis was performed by Monte Carlo simulation. In the ICU patients, higher Vd (nearly twice the quoted value of 0.72 l/kg) and different vancomycin clearance–creatinine clearance relationship were found. Renal function, the APACHE score, age and serum albumin accounted for more than 65% of drug clearance variability. Vancomycin standard dosages led to a 33% risk of not achieving the recommended AUC24h/MIC breakpoint for Staphylococcus aureus.

Conclusions

The population kinetics and PK/PD analyses based on Monte Carlo simulation procedures offer an excellent tool for selecting the therapeutic option with the highest probability of clinical success in ICU patients.

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. Johnson AP, Henwood C, Mushtaq S, James D, Warner M, Livermore DM, The ICU Study Group (2003) Susceptibility of Gram-positive bacteria from ICU patients in UK hospitals to antimicrobial agents. J Hosp Infect 54:179–187 DOI 10.1016/S0195-6701(03)00145-2

    Article  PubMed  CAS  Google Scholar 

  2. Streit JM, Jones RN, Sader HS, Fritsche TR (2004) Assessment of pathogen occurrences and resistance profiles among infected patients in the intensive care unit: report from the SENTRY Antimicrobial Surveillance Program (North America, 2001). Int J Antimicrob Agents 24:111–118 DOI 10.1016/j.ijantimicag.2003.12.019

    Article  PubMed  CAS  Google Scholar 

  3. Jones ME, Draghi DC, Thornsberry C, Karlowsky JA, Sahm DF, Wenzel RP (2004) Emerging resistance among bacterial pathogens in the intensive care unit – a European and North American surveillance study (2000–2002). Ann Clin Microb Antimicrob 3:14 DOI 10.1186/1476-0711-3-14

    Article  CAS  Google Scholar 

  4. Power BM, Forbes AM, van Heerden VP, Ilett KF (1998) Pharmacokinetics of drug used in critically ill adults. Clin Pharmacokinet 34:25–56

    Article  PubMed  CAS  Google Scholar 

  5. Pea F, Porreca L, Baraldo M, Furlanut M (2000) High vancomycin dosage regimens required by intensive care unit patients cotreated with drugs to improve haemodynamics following cardiac surgical procedures. J Antimicrob Chemother 45:329–335

    Article  PubMed  CAS  Google Scholar 

  6. Polard E, Le Bouquin V, Le Corre P, Kérebel C, Trout H, Feuillu A, Le Verge R, Mallédant Y (1999) Non steady state and steady state PKS Bayesian forecasting and vancomycin pharmacokinetics in ICU adult patients. Ther Drug Monit 21:395–403

    Article  PubMed  CAS  Google Scholar 

  7. Mulla H, Pooboni S (2005) Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation. Br J Clin Pharmacol 60:265–275 DOI 10.1111/j.1365-2125.2005.02432.x

    Article  PubMed  CAS  Google Scholar 

  8. DelDot ME, Lipman J, Tett SE (2004) Vancomycin pharmacokinetics in critically ill patients receiving continuous venovenous haemodiafiltration. Br J Clin Pharmacol 58:259–268 DOI 10.1111/j1365-2125.2004.02143.x

    Article  PubMed  CAS  Google Scholar 

  9. Sánchez Navarro A, Sánchez Recio MM (1999) Basis of anti-infective therapy: pharmacokinetic–pharmacodynamic criteria and methodology for dual dosage individualisation. Clin Pharmacokinet 37:289–304

    Article  Google Scholar 

  10. Moise-Broder PA, Forrest A, Birmingham C, 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 

  11. Cockroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41

    Article  Google Scholar 

  12. Jelliffe RW (1973) Creatinine clearance: beside estimate. Ann Inter Med 79:604–605

    CAS  Google Scholar 

  13. Levey AS, Bosch JP, Breger Lewis J, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 130:461–470

    PubMed  CAS  Google Scholar 

  14. Matzke GR (1992) Vancomycin. In: Evans WE, Schentag JJ, Jusko WJ (eds) Applied pharmacokinetics. Principles of therapeutic drug monitoring. Applied Therapeutics, Vancouver, pp 1–31

    Google Scholar 

  15. Bonate PL (2001) A brief introduction to Monte Carlo simulation. Clin Pharmacokinet 40:15–22

    Article  PubMed  CAS  Google Scholar 

  16. Mouton JW, Schmitt-Hoffman A, Shapiro S, Nashed N, Punt NC (2004) Use of Monte Carlo simulations to select therapeutic doses and provisional breakpoints of BAL9141. Antimicrob Agents Chemother 48:1713–1718

    Article  PubMed  CAS  Google Scholar 

  17. Sánchez Navarro A (2005) Optimización de la terapia antibacteriana mediante análisis farmacocinético/farmacodinámico: predicción de la eficacia con técnicas de simulación de Montecarlo. Rev Esp Quimioterap 18:230–235

    Google Scholar 

  18. Kantzanou K, Tassios PT, Tseleni-Kotsovili A, Legakis NJ, Vatopoulos AC (1999) Reduced susceptibility to vancomycin of nosocomial isolates of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother 43:729–731

    Article  PubMed  CAS  Google Scholar 

  19. http://www.simularsoft.com.ar/

  20. Matzke GR, Mc Gory RW, Halstenson CE, Keane WF (1984) Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrob Agents Chemother 25:433–437

    PubMed  CAS  Google Scholar 

  21. Rybak MJ, Boike SC (1986) Monitoring vancomycin therapy. DICP 20:757–761

    CAS  Google Scholar 

  22. Birt JK, Chandler MHH (1990) Using clinical data to determine vancomycin dosing parameters. Ther Drug Monit 12:206–209

    Article  PubMed  CAS  Google Scholar 

  23. Ducharme MP, Slaughter RL, Edwards DJ (1994) Vancomycin pharmacokinetics in a patient population: effect of age, gender and body weight. Ther Drug Monit 16:513–518

    Article  PubMed  CAS  Google Scholar 

  24. Kitzes-Cohen R, Farin D, Piva G, Ivry S, Scharony R, Amar R, Uretzky G (2000) Pharmacokinetics of vancomycin administered as prophylaxis before cardiac surgery. Ther Drug Monit 22:661–667

    Article  PubMed  CAS  Google Scholar 

  25. Rushing TA, Ambrose PJ (2001) Clinical application and evaluation of vancomycin dosing in adults. J Pharm Technol 17:33–38

    CAS  Google Scholar 

  26. De Paepe P, Belpaire FM, Buylaert A (2002) Pharmacokinetic and pharmacodynamic considerations when treating patiens with sepsis and septic shock. Clin Pharmacokinet 41:1135–1151

    Article  PubMed  Google Scholar 

  27. Zellner D, Zellner GE, Keller F (1998) Dependence of vancomycin clearance on renal function via regression and bootstrap methods. J Clin Pharm Ther 23:107–113

    PubMed  CAS  Google Scholar 

  28. Ambrose PG, Quintiliani R (2000) Limitations of single point pharmacodynamic analysis. Pediatr Infect Dis J 19:769

    PubMed  CAS  Google Scholar 

  29. Schentag JJ (2001) Antimicrobial management strategies for Gram-positive bacterial resistance in the intensive care unit. Crit Care Med 29(suppl 4):S100–S107

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank the staff of the Intensive Care Medicine Department of the University Hospital of Salamanca for use of their facilities and collaboration.

Author information

Authors and Affiliations

  1. Pharmacy Department, University of Salamanca, Salamanca, Spain

    Maria del Mar Fernández de Gatta Garcia, Maria Victoria Calvo, Alfonso Domínguez-Gil & Amparo Sánchez Navarro

  2. University Hospital of Salamanca, Salamanca, Spain

    Natalia Revilla, Maria Victoria Calvo & Alfonso Domínguez-Gil

Authors
  1. Maria del Mar Fernández de Gatta Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Natalia Revilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Victoria Calvo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alfonso Domínguez-Gil
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Amparo Sánchez Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria del Mar Fernández de Gatta Garcia.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

del Mar Fernández de Gatta Garcia, M., Revilla, N., Calvo, M.V. et al. Pharmacokinetic/pharmacodynamic analysis of vancomycin in ICU patients. Intensive Care Med 33, 279–285 (2007). https://doi.org/10.1007/s00134-006-0470-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-006-0470-5

Keywords

Search

Navigation