To identify the variables affecting vancomycin pharmacokinetics in medical ICU patients and to evaluate the potential efficacy of dosage schedules by PK/PD analysis.
A retrospective pharmacokinetic analysis of serum levels obtained in routine vancomycin monitoring was performed.
A 12-bed general ICU of a university teaching hospital.
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.
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.
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.
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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
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
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
Power BM, Forbes AM, van Heerden VP, Ilett KF (1998) Pharmacokinetics of drug used in critically ill adults. Clin Pharmacokinet 34:25–56
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
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
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
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
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
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
Cockroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41
Jelliffe RW (1973) Creatinine clearance: beside estimate. Ann Inter Med 79:604–605
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
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
Bonate PL (2001) A brief introduction to Monte Carlo simulation. Clin Pharmacokinet 40:15–22
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
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
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
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
Rybak MJ, Boike SC (1986) Monitoring vancomycin therapy. DICP 20:757–761
Birt JK, Chandler MHH (1990) Using clinical data to determine vancomycin dosing parameters. Ther Drug Monit 12:206–209
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
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
Rushing TA, Ambrose PJ (2001) Clinical application and evaluation of vancomycin dosing in adults. J Pharm Technol 17:33–38
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
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
Ambrose PG, Quintiliani R (2000) Limitations of single point pharmacodynamic analysis. Pediatr Infect Dis J 19:769
Schentag JJ (2001) Antimicrobial management strategies for Gram-positive bacterial resistance in the intensive care unit. Crit Care Med 29(suppl 4):S100–S107
The authors thank the staff of the Intensive Care Medicine Department of the University Hospital of Salamanca for use of their facilities and collaboration.
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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
- ICU patients
- Population kinetics
- Dosage optimisation
- PK/PD analysis
- Monte Carlo simulation