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Meropenem therapy in extracorporeal membrane oxygenation patients: an ongoing pharmacokinetic challenge

We agree with the recent commentary of Gonçalves-Pereira and Oliveira refuting a ‘one size fits all’ paradigm of antibiotic dosing in patients subjected to extracorporeal circulation [1] but want to focus somewhat further on meropenem pharmacokinetics (PK).

Meropenem has optimal bactericidal activity if plasma levels remain above the minimum inhibitory concentration of the pathogen for at least 40 % of the dosing interval. Still, many patients with severe sepsis do not attain this PK target, have unpredictable PK changes or show large individual and inter-patient variability in distribution volume and clearance when treated with recommended meropenem doses [2, 3].

Meropenem is degraded and significantly sequestered in the extracorporeal membrane oxygenation (ECMO) circuit after 4 to 6 h of treatment. ECMO also induces a systemic inflammatory response which, independently of underlying sepsis, impairs normal meropenem PK [4]. Thus, optimization of meropenem treatment during ECMO requires either more frequent dosing, a dose increase, or prolonged infusion. Ideally, meropenem should be infused continuously over 24 h but, due to its relative instability at room temperature, only a 3-hour infusion is safely feasible. We suggest to administer a 3-hour infusion of 2 g meropenem every 6 h [4]. Future adaptations must be anticipated. We refer to the recently proposed concept of ‘dose modulation’, which concentrates the largest weight of antibiotics front-end when the microbial load is highest and gradually reduces antibiotic dose as sepsis improves [5]. This would imply increasing the loading dose of meropenem (4 g?) and ensuring an adequate maintenance dose guided by PK parameters.

Abbreviations

ECMO:

Extracorporeal membrane oxygenation

PK:

Pharmacokinetics

References

  1. 1.

    Gonçalves-Pereira J, Oliveira B. Antibiotics and extracorporeal circulation - one size does not fit all. Crit Care. 2014;18:695.

  2. 2.

    Taccone FS, Laterre PF, Dugernier T, Spapen H, Delattre I, Witebolle X, et al. Insufficient β- lactam concentrations in the early phase of severe sepsis and septic shock. Crit Care. 2010;14:R126.

  3. 3.

    Roberts JA, Kirkpatrick CM, Roberts MS, Robertson TA, Dalley AJ, Lipman J. Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. J Antimicrob Chemother. 2009;64:142–50.

  4. 4.

    Honore PM, Jacobs R, Spapen HD. Antimicrobial dosing during extracorporeal membrane oxygenation. In: Vincent JL, editor. Annual update on intensive care and emergency care. Cham: Springer International Publishing; 2014. p. 43–53.

  5. 5.

    Gonçalves-Pereira J, Paiva JA. Dose modulation: a new concept of antibiotic therapy in the critically ill patient ? J Crit Care. 2013;28:341–6.

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Author information

Correspondence to Patrick M. Honore.

Additional information

Competing interests

The authors declare that they have no competing interests.

See related commentary by Gonçalves-Pereira and Oliveira, http://ccforum.com/content/18/6/695

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Honore, P.M., Jacobs, R., Hendrickx, I. et al. Meropenem therapy in extracorporeal membrane oxygenation patients: an ongoing pharmacokinetic challenge. Crit Care 19, 263 (2015). https://doi.org/10.1186/s13054-015-0953-2

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Keywords

  • Meropenem
  • Extracorporeal Membrane Oxygenation
  • Extracorporeal Circulation
  • Microbial Load
  • Dose Modulation