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VOLUME 23 , ISSUE 11 ( November, 2019 ) > List of Articles

Original Article

Single-dose and Steady-state Pharmacokinetics of Vancomycin in Critically Ill Patients Admitted to Medical Intensive Care Unit of India

Nitin B Mali, Siddharth P Deshpande, Poorwa P Wandalkar, Vishal A Gupta, Niteen D Karnik, Nithya J Gogtay, Gita Nataraj, Preeti R Mehta, Urmila Thatte

Keywords : Critically ill, Methicillin resistance Staphylococcus aureus, Pharmacokinetics–pharmacodynamics, Single and steady state, Vancomycin

Citation Information : Mali NB, Deshpande SP, Wandalkar PP, Gupta VA, Karnik ND, Gogtay NJ, Nataraj G, Mehta PR, Thatte U. Single-dose and Steady-state Pharmacokinetics of Vancomycin in Critically Ill Patients Admitted to Medical Intensive Care Unit of India. Indian J Crit Care Med 2019; 23 (11):513-517.

DOI: 10.5005/jp-journals-10071-23289

License: CC BY-NC 4.0

Published Online: 00-11-2019

Copyright Statement:  Copyright © 2019; Jaypee Brothers Medical Publishers (P) Ltd.


Abstract

Rationale: Vancomycin remains the standard of care for gram-positive bacterial infections, though there are significant developments in newer antibacterial agents. Efficacy can be improved by linking pharmacokinetic with pharmacodynamic principles, thus leading to optimum antibiotic exposure. There is scarcity of pharmacokinetic data in Indian intensive care unit (ICU) population. Materials and methods: Fifteen subjects with suspected or proven gram-positive bacterial infection of either gender between 18 years and 65 years of age were enrolled. Vancomycin at the dose of 1 g every 12 hours was administered over 1-hour period and pharmacokinetic assessments performed on blood samples collected on days 1 and 3. Vancomycin concentrations were measured on validated liquid chromatography mass spectrometry method. Pharmacokinetic parameters were calculated using Winnonlin (Version 6.3; Pharsight, St. Louis, MO). Results: The mean Cmax, elimination half-life, AUC0–12hours, volume of distribution, and clearance of single dose were 36.46 μg/mL (±14.87), 3.98 hours (±1.31), 113.51 μg/mL (±49.51), 52.01 L (±31.31), and 8.90 mL/minute (±3.29), respectively, and at steady state were 40.87 μg/mL (±19.29), 6.27 hours (±3.39), 147.94 μg/mL (±72.89), 56.39 L (±42.13), and 6.98 mL/minute (±4.48), respectively. The elimination half-life increased almost two-fold at steady state. The steady state mean AUC0–24 was 295.89 µg/mL (±153.82). Out of 45 trough levels, 32 (71.11%) concentrations were below recommended range. Conclusion: Recommended AUC0–24hours and trough concentrations were not achieved in majority of patients with current dosing, suggesting reevaluation of current vancomycin dosing. Individualized treatment based on close monitoring of vancomycin serum concentrations in critically ill patients is imperative.


  1. Levine DP. Vancomycin: a history. Clin Infect Dis 2006;42(Suppl 1): S5–S12. DOI: 10.1086/491709.
  2. Vandecasteele SJ, De Vriese AS, Tacconelli E. The pharmacokinetics and pharmacodynamics of vancomycin in clinical practice: evidence and uncertainties. J Antimicrob Chemother 2013;68(4):743–748. DOI: 10.1093/jac/dks495.
  3. Del Mar Fernandez De Gatta Garcia M, Revilla N, Calvo MV, et al. Pharmacokinetic/pharmacodynamic analysis of vancomycin in ICU patients. Intensive Care Med 2007;33(2):279–285. DOI: 10.1007/s00134-006-0470-5.
  4. Revilla N, Martín-Suárez A, Pérez MP, et al. Vancomycin dosing assessment in intensive care unit patients based on a population pharmacokinetic/pharmacodynamic simulation. Br J Clin Pharmacol 2010;70(2):201–212. DOI: 10.1111/j.1365-2125.2010.03679.x.
  5. Sarin MSK, Vadivelan M, Bammigatti C. Antimicrobial therapy in the intensive care unit. Indian J Clin Pract 2013;23(10):601–609.
  6. Cantón R, Horcajada JP, Oliver A, et al. Inappropriate use of antibiotics in hospitals: the complex relationship between antibiotic use and antimicrobial resistance. Enferm Infecc Microbiol Clin 2013;31(Suppl 4): 3–11. DOI: 10.1016/S0213-005X(13)70126-5.
  7. Indian Network for Surveillance of Antimicrobial Resistance (INSAR) Group I. Methicillin resistant staphylococcus aureus (MRSA) in india: prevalence & Susceptibility pattern Indian network for surveillance of antimicrobial resistance (INSAR) group, india. Indian J Med Res 2013;137:363–369.
  8. Praharaj I, Sujatha S, Chandra Parija S. Phenotypic & genotypic characterization of vancomycin resistant enterococcus isolates from clinical specimens. Indian J Med Res 2013;138:549–556.
  9. Phukan C, Lahkar M, Ranotkar S, et al. Emergence of van A gene among vancomycin-resistant enterococci in a tertiary care hospital of north - east India. Indian J Med Res 2016;143(3):357–361. DOI: 10.4103/0971-5916.182627.
  10. Rybak M, Lomaestro B, Rotschafer JC, 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(1):82–98. DOI: 10.2146/ajhp080434.
  11. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant staphylococcus aureus infections in adults and children. Clin Infect Dis 2011;52(3):1–38. DOI: 10.1093/cid/ciq146.
  12. Mali NB, Deshpande SP, Karnik ND, et al. Multicentric, prospective, observational antibacterial utilization study in Indian tertiary referral centers. Indian J Crit Care Med 2018;22(10):723–729. DOI: 10.4103/ijccm.IJCCM_197_18.
  13. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16(1):31–41. DOI: 10.1159/000180580.
  14. https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__Step_4_2016_1109.pdf.
  15. Zhang T, Watson DG, Azike C, et al. Determination of vancomycin in serum by liquid chromatography-high resolution full scan mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 2007;857(2):352–356. DOI: 10.1016/j.jchromb.2007.07.041.
  16. Food and Drug Administration (2001) Guidance for Industry: Bioanalytical method validation. (https://www.fda.gov/downloads/drugs/guidances/ucm368107.pdf).
  17. Gabrielsson J, Weiner D. Non-compartmental analysis. Computational toxicology. Methods Mol Biol 2012;929:377–389. DOI: 10.1007/978-1-62703-050-2_16.
  18. Matzke GR, Kovarik JM, Rybak MJ, et al. Evaluation of the vancomycin clearance: creatinine-clearance relationship for predicting vancomycin dosage. Clin Pharm 1985;4:311–315.
  19. Blot S, Koulenti D, Akova M, et al. Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study. Crit Care 2014;18(3):1–11. DOI: 10.1186/cc13874.
  20. Marinho DS, Huf G, La FB, et al. The study of vancomycin use and its adverse reactions associated to patients of a Brazilian university hospital. BMC Res Notes 2011;4(1):1–6. DOI: 10.1186/1756-0500-4-236.
  21. Healy DP, Polk RE, Garson ML, et al. Comparison of steady-state pharmacokinetics of two dosage regimens of vancomycin in normal volunteers. Antimicrob Agents Chemother 1987;31(3):393–397. DOI: 10.1128/AAC.31.3.393.
  22. Polard E, Le Bouguin V, Le Corre P, et al. Non steady state and steady state PKS Bayesian forecasting and vancomycin pharmacokinetics in ICU adult patients. Ther Drug Monit 1999;21(4):395–403. DOI: 10.1097/00007691-199908000-00003.
  23. Dedkaew T, Cressey TR, Punyawudho B, et al. Pharmacokinetics of vancomycin in critically ill patients in Thailand. Int J Pharm Pharm Sci 2015;7(9):232–237.
  24. Van DR, Vree TB. Intensive care medicine pharmacokinetics of antibiotics in critically ill patients. Trauma 1990; 235–238.
  25. Triginer C, Izquierdo I, Fernfindez R, et al. Intensive care medicine gentamicin volume of distribution in critically ill septic patients. Intensive Care Med 1990;16:303–306. DOI: 10.1007/BF01706354.
  26. Tod M, Padoin C, Minozzi C, et al. Population pharmacokinetic study of isepamicin with intensive care unit patients. Antimicrob Agents Chemother 1996;40(4):983–987. DOI: 10.1128/AAC.40.4.983.
  27. Power BM, Forbes AM, van PV, et al. Pharmacokinetics of drugs used in critically ill adults. Clin Pharmacokinet 1998;34(1):25. DOI: 10.2165/00003088-199834010-00002.
  28. Rybak MJ. The pharmacokinetic and pharmacodynamic properties of vancomycin. Clin Infect Dis 2006;42(Suppl 1):S35–S39. DOI: 10.1086/491712.
  29. Leader WG, Chandler MHH, Castiglia M. Pharmacokinetic optimisation of vancomycin therapy. Clin Pharmacokinet 1995;28(4):327–342. DOI: 10.2165/00003088-199528040-00005.
  30. Rodvold KA, Blum RA, Fischer JH, et al. Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrob Agents Chemother 1988;32(6):848–852. DOI: 10.1128/AAC.32.6.848.
  31. Moise-Broder PA, Forrest A, Birmingham MC, et al. Pharmacodynamics of vancomycin and other antimicrobials in patients with staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet 2004;43(13):925–942. DOI: 10.2165/00003088-200443130-00005.
  32. Shahrami B, Najmeddin F, Mousavi S, et al. Achievement of vancomycin therapeutic goals in critically ill patients: early individualization may be beneficial. Crit Care Res Pract 2016; 1–7. DOI: 10.1155/2016/1245815.
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