PHARMACOKINETICS OF VANCOMYCIN IN CRITICALLY ILL PATIENTS IN THAILAND
Objective: The pharmacokinetics and pharmacodynamics of drugs in critically ill patients are difficult to predict due to complex pathophysiological changes. Vancomycin is an antibiotic commonly used to treat serious gram positive bacterial infections in critically ill patients and the treatment goal is to rapidly achieve and maintain therapeutic concentrations. We assessed the pharmacokinetics of vancomycin in critically ill patients to help guide dosing.
Methods: A total of 138 patients with 299 vancomycin serum concentrations were included in this analysis. Vancomycin serum concentrations were measured using a fluorescence polarization immunoassay. Population pharmacokinetic parameters were estimated using nonlinear mixed effects regression. Age, creatinine clearance (CrCL) and body weight were tested as potential covariates in the pharmacokinetic model.
Results: Vancomycin concentration-time profiles were best described by a two-compartment pharmacokinetic model with an additive error model for between subject variability. Creatinine clearance significantly influenced vancomycin clearance (CL). Mean population pharmacokinetic parameters (% between subject variability) were: CL 3.39 l/h (13%), central compartment volume of distribution (V1) 24.92 l (26%); and peripheral compartment volume of distribution (V2) 24.6 (37%).
Conclusion: Higher clearance and a smaller volume of distribution of vancomycin was observed in critically-ill patients compared to those reported in non-critically ill patients with a similar distribution of renal function and body weight. Close monitoring of vancomycin serum concentrations is warranted in critically ill patients with dose interval adjustments based on the patientâ€™s creatinine clearance.
2. McEvoy GK. editor. Vancomycin Hydrochloride. In: AHFS Drug Information. 43rd ed. Bethesda MD. American Society of Health-System Pharmacists; 2003. p. 457-64.
3. Rodvold KA, Erdman SM, Pryka RD. Vancomycin. In: Schumacker GE. editor. Therapeutic Drug Monitoring. 1st ed. Connecticut: Appleton & Lange; 1995. p. 587-632.
4. Lacy CF, Armstrong LL, Goldman MP, Lance LL. editors. Vancomycin. Drug Information Handbook: A Comprehensive Resource for All Clinicians and Heathcare Professionals.19th ed. Ohio: Lexi-Comp, Inc; 2010. p. 1599-602.
5. Petrosillo N, Drapeau CM, Agrafiotis M, Falaqas ME. Some current issues in the pharmacokinetics/pharmacodynamics of antimicrobials in intensive care. Minerva Anestesiol 2010;76:508-23.
6. Rybak MJ. The pharmacokinetic and pharmacodynamics properties of vancomycin. Clin Infect Dis 2006;4(2suppl 1):S35-9.
7. Antonelli M, Azoulay E, Bonten M, Chasre J, Citerio G, Conti G, et al. Year in review in Intensive Care Medicine, 2007. II. Haemodynamics, pneumonia, infections and sepsis, invasive and non-invasive mechanical ventilation, acute respiratory distress syndrome. Intensive Care Med 2008;34:405-22.
8. del Mar Fernandez, de Gatta Garcia M, Revilla N, Calvo MV, Dominguez-Gil A, Navarro AS. Pharmacokinetic/ pharmacodynamics analysis of vancomycin in ICU patients. Intensive Care Med 2007;33:279-85.
9. Brown DL, Lalla CD, Masselink AJ. AUC versus peak-trough dosing of vancomycin: applying new pharmacokinetic paradigms to an old drug. Ther Drug Monit 2013;35:443-9.
10. Rybak MJ, Lomaestro B, Rotschafer JC, Moellering RC, Craig WA, 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.
11. Cruciani M, Gatti G, Lazzarini L, Furlan G, Broccali G, Malena M, et al. Penetration of vancomycin into human lung tissue. J Antimicrob Chemother 1996;38:865-9.
12. Blouin RA, Bauer LA, Miller DD, Record KE, Griffen WO Jr. Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrob Agents Chemother 1982;21:575-80.
13. Cutler NR, Narang PK, Lesko LJ, Ninos M, Power M. Vancomycin disposition: The importance of age. Clin Pharmacol Ther 1984;36:803-10.
14. Miller JR, Garner AW. Unpredictable vancomycin excretion in an elderly patient with adequate renal function. ASHP Midyear Clinical Meeting 1990;25:HP-181D.
15. Marchaim D, Kaye KS, Fowler VG, Anderson DJ, Chawla V, Golan Y, et al. Case-control study to identify factors associated with mortality among patients with methicillin-resistant Staphylococcus aureus bacteremia. Clin Microbiol Infect 2010;16:747-52.
16. Masterton R, Drusano G, Paterson DL, Park G. Appropriate antimicrobial treatment in nosocomial infections-the clinical challenges. J Hospital Infection 2003;55 Suppl 1:1-12.
17. Mahoney K, Browning LA, Hall LG. An evaluation of a validated vancomycin dosing nomogram in the critically ill population. Crit Care Med 2006;34:A153.
18. Maclayton DO, Hall RN. Pharmacologic treatment options for nosocomial pneumonia involving methicillin-resistant Staphylococcus aureus. Ann Pharmacother 2007;41:235-44.
19. Patanwala A, Norris CJ, Nix DE, Kopp BJ, Erstad BL. Vancomycin dosing for pneumonia in critically ill trauma patients. J Trauma 2009;67:802-4.
20. Roberts JA, Roberts MS, Robertson TA, Dalley AJ, Lipman J. Piperacillin penetration into tissue of critically ill patients with sepsis-Bolus vs continuous administration. Crit Care Med 2009;37:926-33.
21. Fry D. The importance of antibiotic pharmacokinetics in critical illness. Am J Surg 1996;172 Suppl 6:S20-5.
22. Scaglione F, Paraboni L. Review Pharmacokinetics/ pharmacodynamics of antibacterials in the Intensive Care Unit: setting appropriate dosing regimens. Int J Antimicrob Agents 2008;32:294-301.
23. Sanchez JL, Dominguez AR, Lane JR, Anderson PO, Capparelli EV, Cornejo-Bravo JM. Population pharmacokinetics of vancomycin in adult and geriatric patients: comparison of eleven approaches. Int J Clin Pharmacol Ther 2010;48:525-33.
24. Yamamoto M, Kuzuya T, Baba H, Yamada K, Nabeshima T. Population pharmacokinetic analysis of vancomycin in patients with gram-positive infections and the influence of infectious disease type. J Clin Pharm Ther 2009;34:473-83.
25. Yasuhara M, Ig 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.
26. Llopis-Salvia P, Jimenez-Torres NV. Population pharmacokinetic parameters of vancomycin in critically ill patients. J Clin Pharm Ther 2006;31:447-54.
27. Polard E, Le Bouquin V, Le Corre P, Kerebel C, Trout H, Feuillu A, et al. Non steady state and steady state PKS Baysian forecasting and vancomycin pharmacokinetics in ICU adult patients. Ther Drug Monit 1999;21:395-403.
28. Purwonugroho TA, Chulavatnatol S, Preechagoon Y, Chindavijak B, Malthum K, Bunuparadah P. Population pharmacokinetics of vancomycin in Thai patients. Sci World J 2012;2012:1-8.
29. Thomson AH, Staatz CE, Tobin CM, Gall M, Lovering AM. Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations. J Antimicrob Chemother 2009;63:1050-7.
30. American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171:388-416.