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Pharmacokinetics of meropenem during intermittent and continuous intravenous application in patients treated by continuous renal replacement therapy

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Abstract

Objective

The clinical effect of beta-lactam antibiotics depends on the time of drug concentration above the minimal inhibitory concentration (MIC) for a susceptible bacterium. Continuous infusion (CI) of ß-lactams such as meropenem may therefore be a more rational approach than intermittent bolus injections (IB). The aim of this study was to test whether CI of meropenem achieves effective drug concentrations comparable to IB in patients treated by continuous renal replacement therapy (CRRT).

Design

Prospective, randomised cross-over study.

Setting

Twelve-bed medical intensive care unit (ICU).

Patients and interventions

Six ICU patients were randomised to receive either meropenem 1 g IB every 12 h or a 0.5 g i.v. loading dose followed by 2 g i.v. CI over 24 h. After 2 days, regimens were crossed over. Meropenem pharmacokinetics were determined on days 2 and 4.

Measurements and results

Peak serum concentration [median (25% and 75% quartiles)] after short infusion of 1 g meropenem were 62.8 (51.4; 85.0) mg/l, trough levels at 12 h were 8.1 (4.5; 18.7) mg/l, and serum half-life was 5.3 (5.1; 7.0) h. Steady-state concentrations during CI were 18.6 (13.3; 24.5) mg/l. The AUCs during either treatment were comparable and determined as 233 (202; 254) mg/l*h (IB) and 227 (182; 283) mg/l*h (CI), respectively. Four hours after IB, drug concentrations dropped below CI steady-state concentrations.

Conclusion

Appropriate antibacterial concentrations of meropenem in patients with CRRT are easily achievable with CI. CI may be an effective alternative dosing regimen to IB. A prospective comparison of the clinical efficacy of the two dosage regimens is warranted.

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Acknowledgements

Thanks to Carl Waldman for his stimulating comments on our work.

This work was supported by a grant from AstraZeneca for pharmacokinetic analysis.

Author information

Authors and Affiliations

  1. Department of Internal Medicine I, University of Regensburg, 93042, Regensburg, Germany

    Julia Langgartner & Antje Vasold

  2. Department of Internal Medicine, General Hospital Traunstein, Postfach 1820, 83276, Traunstein, Germany

    Thomas Glück

  3. Department of Internal Medicine, General Hospital Bogen, Mussinanstr. 8, 94327, Bogen, Germany

    Michel Reng

  4. Department of Pharmacology, University of Regensburg, 93053, Regensburg, Germany

    Frieder Kees

Authors
  1. Julia Langgartner
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  2. Antje Vasold
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  3. Thomas Glück
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  4. Michel Reng
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  5. Frieder Kees
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Corresponding author

Correspondence to Julia Langgartner.

Additional information

The authors wrote this article in cooperation with the TAHI section of the ESICM.

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Langgartner, J., Vasold, A., Glück, T. et al. Pharmacokinetics of meropenem during intermittent and continuous intravenous application in patients treated by continuous renal replacement therapy. Intensive Care Med 34, 1091–1096 (2008). https://doi.org/10.1007/s00134-008-1034-7

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  • DOI: https://doi.org/10.1007/s00134-008-1034-7

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