Background : Sepsis is a severe disease with complex pathophysiology and high mortality. Meropenem is frequently used in sepsis to treat the underlying infection. Studies have shown that standard doses of meropenem are frequently inadequate due to high pharmacokinetic and pharmacodynamic variability. Therapeutic drug monitoring (TDM) of meropenem is not widely available, and increased empiric dosing recommendations are needed. Methods : We compared two empiric dosing schemes of meropenem using extended infusion (120 minutes) in 32 patients with sepsis in the ICUs at two different hospitals. One regimen was 3x 2 g meropenem/ 24 h for two days, followed by 3x 1 g meropenem/ 24 h; the other regimen was 4x 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 dosing interval 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 4x 1 g meropenem decreased faster than that of 3x 2 g meropenem. At high MICs of 32 mg/L, both dosing regimens failed to provide drug concentrations deemed appropriate for clinical improvement. Conclusions : The results of this pilot study can guide clinicians in their choice of an empirical dosing scheme when prescribing meropenem in the absence of TDM. If pathogens with low MICs (<4 mg/L) are targeted, both dosing regimens are adequate, whereas more resistant clones require higher doses. The control of β-lactam therapy by therapeutic drug monitoring is desirable.
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