Advertisement

Critical Care

, 23:15 | Cite as

Vancomycin pharmacokinetics in critically ill obese patients: can the clinician sit back and relax?

  • Patrick M. HonoreEmail author
  • David De Bels
  • Luc Kugener
  • Sebastien Redant
  • Rachid Attou
  • Andrea Gallerani
  • Herbert D. Spapen
Open Access
Letter

Abbreviations

AUC

Area under the concentration-time curve

CIV

Continuous infusion of vancomycin

MIC

Minimum inhibitory concentration

MRSA

Methicillin-resistant Staphylococcus aureus

PK

Pharmacokinetic

The recently published study by Lin et al. provides valid pharmacokinetic (PK) data regarding continuous infusion of vancomycin (CIV) in obese versus non-obese patients. An important finding is that CIV in obese patients, whether or not receiving renal replacement therapy, consistently produced target “therapeutic” serum concentrations and resulted in a lower weight-based daily vancomycin exposure as compared to non-obese subjects [1].

A shortcoming of this study is the lack of information on bacterial susceptibility to vancomycin. Vancomycin achieves a near maximal bactericidal effect when the ratio of the vancomycin area under the concentration-time curve (AUC) over the minimum inhibitory concentration (MIC) exceeds 400 [2]. However, vancomycin exerts slow bactericidal activity and has low tissue penetration, and serum levels poorly correlate with microbiological or clinical success. Moreover, high vancomycin MICs, irrespective of testing methodology and infection source, are predictive for treatment failure and associated with a higher mortality rate [3]. Vancomycin trough concentrations of 15 mg/L (with intermittent administration) or steady state concentrations of 20 to 30 mg/L (with CIV) act as surrogates of an AUC/MIC ≥ 400, assuming a vancomycin MIC of ≤ 1 mg/L. The majority of cultured bacteria in the study of Lin et al. are coagulase-negative staphylococci which remain largely susceptible to vancomycin in adult patients [4]. Less than 10% of cultures grew methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin may not be useful for treating serious MRSA infections with MIC values > 1 mg/L, and no dosing regimen can reach an AUC/MIC for isolates with a vancomycin MIC ≥ 2 mg/L [3].

Lin et al. also did not assess vancomycin concentrations after the loading dose (approximately 25 mg/kg) and at 24 h. In septic patients, Cristallini et al. [5] applied a loading dose of 35 mg/kg followed by a daily CIV dose adapted to creatinine clearance. Therapeutic concentrations of 20 to 30 mg/L were obtained in 54% of patients after 24 h. Thus, early relevant vancomycin levels were obtained in only half of a representative critically ill patient cohort despite utilizing a substantially higher loading dose and aiming at higher steady state vancomycin concentrations than Lin et al.

From a PK viewpoint, the study of Lin et al. is highly informative, yet some restraint is required before translating these results into clinical scenarios.

Notes

Acknowledgements

None.

Funding

None.

Availability of data and materials

Not applicable.

Authors’ contributions

PMH and HDS designed the paper. All authors participated in drafting and reviewing. All authors read and approved the final version of the manuscript.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  1. 1.
    Lin H, Yeh DD, Levine AR. Daily vancomycin dose requirements as a continuous infusion in obese versus non-obese SICU patients. Crit Care. 2016;20(1):205.CrossRefGoogle Scholar
  2. 2.
    Moise-Broder PA, Forrest A, Birmingham MC, Schentag JJ. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet. 2004;43(13):925–42.CrossRefGoogle Scholar
  3. 3.
    van Hal SJ, Lodise TP, Paterson DL. The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis. Clin Infect Dis. 2012;54(6):755–71.CrossRefGoogle Scholar
  4. 4.
    Paiva RM, Mombach Pinheiro Machado AB, Zavascki AP, Barth AL. Vancomycin MIC for methicillin-resistant coagulase-negative Staphylococcus isolates: evaluation of the broth microdilution and Etest methods. J Clin Microbiol. 2010;48(12):4652–4.CrossRefGoogle Scholar
  5. 5.
    Cristallini S, Hites M, Kabtouri H, Roberts JA, Beumier M, Cotton F, et al. New regimen for continuous infusion of vancomycin in critically ill patients. Antimicrob Agents Chemother. 2016;60(8):4750–6.CrossRefGoogle Scholar

Copyright information

© The Author(s). 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors and Affiliations

  • Patrick M. Honore
    • 1
    Email author
  • David De Bels
    • 1
  • Luc Kugener
    • 1
  • Sebastien Redant
    • 1
  • Rachid Attou
    • 1
  • Andrea Gallerani
    • 1
  • Herbert D. Spapen
    • 2
  1. 1.ICU DepartmentCentre Hospitalier Universitaire Brugmann-Brugmann University HospitalBrusselsBelgium
  2. 2.Medicine, Ageing & Pathology Research GroupVrije Universiteit BrusselBrusselsBelgium

Personalised recommendations