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Observational Study
. 2018 Jan 30;22(1):25.
doi: 10.1186/s13054-018-1940-1.

Pharmacokinetics of meropenem in septic patients on sustained low-efficiency dialysis: a population pharmacokinetic study

Stephan Braune  1 , Christina König  2   3 , Jason A Roberts  4 , Axel Nierhaus  2 , Oliver Steinmetz  5 , Michael Baehr  3 , Stefan Kluge  2 , Claudia Langebrake  3   6
Affiliations
Observational Study

Pharmacokinetics of meropenem in septic patients on sustained low-efficiency dialysis: a population pharmacokinetic study

Stephan Braune et al. Crit Care. .

Abstract

Background: The aim of the study was to describe the population pharmacokinetics (PK) of meropenem in critically ill patients receiving sustained low-efficiency dialysis (SLED).

Methods: Prospective population PK study on 19 septic patients treated with meropenem and receiving SLED for acute kidney injury. Serial blood samples for determination of meropenem concentrations were taken before, during and after SLED in up to three sessions per patient. Nonparametric population PK analysis with Monte Carlo simulations were used. Pharmacodynamic (PD) targets of 40% and 100% time above the minimal inhibitory concentration (f T > MIC) were used for probability of target attainment (PTA) and fractional target attainment (FTA) against Pseudomonas aeruginosa.

Results: A two-compartment linear population PK model was most appropriate with residual diuresis supported as significant covariate affecting meropenem clearance. In patients without residual diuresis the PTA for both targets (40% and 100% f T > MIC) and susceptible P. aeruginosa (MIC ≤ 2 mg/L) was > 95% for a dose of 0.5 g 8-hourly. In patients with a residual diuresis of 300 mL/d 1 g 12-hourly and 2 g 8-hourly would be required to achieve a PTA of > 95% and 93% for targets of 40% f T > MIC and 100% f T > MIC, respectively. A dose of 2 g 8-hourly would be able to achieve a FTA of 97% for 100% f T > MIC in patients with residual diuresis.

Conclusions: We found a relevant PK variability for meropenem in patients on SLED, which was significantly influenced by the degree of residual diuresis. As a result dosing recommendations for meropenem in patients on SLED to achieve adequate PD targets greatly vary. Therapeutic drug monitoring may help to further optimise individual dosing.

Trial registration: Clincialtrials.gov, NCT02287493 .

Keywords: Acute renal failure; Meropenem; Pharmacokinetics; Sepsis; Sustained low-efficiency dialysis.

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Conflict of interest statement

Ethics approval and consent to participate

Ethics approval was obtained from the local ethics committee. Written informed consent was obtained either from the patient or their appointed legal guardian.

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.

Figures

Fig. 1
Fig. 1
Diagnostic plots for the final covariate model. Observed versus individual predicted concentrations
Fig. 2
Fig. 2
Diagnostic plots for the final covariate model. Visual predictive checks
Fig. 3
Fig. 3
Probability of target attainment (PTA) of various meropenem doses for a residual diuresis (RD) of 0 mL/d, 100 mL/d and 300 mL/d for a PD target of 40% f T > MIC (left column) and for a PD target of 100% f T > MIC. (right column)
Fig. 4
Fig. 4
Probability of target attainment (PTA) prolonged (1 g and 2 g 8-hourly) and continuous meropenem (6 g/24 hours) infusions for a residual diuresis (RD) of 0 mL/d, 100 mL/d and 300 mL/d for a PD target of 100% f T > MIC
Fig. 5
Fig. 5
PK profile of meropenem at a dose of 2 g 8-hourly in patients with a residual diuresis of 300 ml/d. Time (hours) displayed on the x-axis, concentrations (mg/L) displayed on the y-axis
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