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Prolonged infusion dosing regimens for meropenem in sepsis patients

"The results of this study can guide clinicians in their choice of an empirical dosing regimen for meropenem" Eisert et al (2021).

Abstract:

Background: Standard doses of meropenem are frequently inadequate in septic patients due to high pharmacokinetic variability. Therapeutic drug monitoring (TDM) of meropenem is not widely available, therefore improved empiric dosing recommendations are needed.

Objectives: The purpose of this study was to compare the attainment of pharmacologic targets for two common empirical dosing regimens for meropenem in patients with septic shock.

Methods: We compared two empiric dosing schemes for meropenem using extended infusions (120 minutes) in 32 patients with septic shock in the ICUs at two different hospitals. One regimen was 3×2 g meropenem/ 24 h for two days, followed by 3×1 g meropenem/ 24 h; the other regimen was 4×1 g meropenem/ 24 h. Serum meropenem concentrations were measured for the first 72 h of therapy, and pharmacokinetic modelling was performed to define the percentage of time the free drug concentration was above various target minimal inhibitory concentrations (MICs) for each regimen (%fT>MIC).

Results: Both regimens led to a sufficiently high %fT>MIC for pathogens with target MICs below 4 mg/L. When higher MICs were targeted, the %fT>MIC of 4×1 g meropenem decreased faster than that of 3×2 g meropenem. At high MICs of 32 mg/L, both dosing regimens failed to provide appropriate drug concentrations. Renal function was a significant covariate of target attainment.

Conclusions: The results of this study can guide clinicians in their choice of an empirical dosing regimen for meropenem. If pathogens with low MICs (<4 mg/L) are targeted, both dosing regimens are adequate, whereas more resistant strains require higher doses.

Reference:

Eisert A, Lanckohr C, Frey J, Frey O, Wicha SG, Horn D, Ellger B, Schuerholz T, Marx G, Simon TP. Comparison of two empirical prolonged infusion dosing regimens for meropenem in patients with septic shock: A two-center pilot study. Int J Antimicrob Agents. 2021 Jan 27:106289. doi: 10.1016/j.ijantimicag.2021.106289. Epub ahead of print. PMID: 33515688.