Pharmacokinetics of imipenem in critically ill patients: Continuous infusion versus extended infusion in a real-world...

ObjectiveThis study compared the pharmacokinetic/pharmacodynamic properties of extended infusion and continuous infusion of imipenem at equivalent daily doses in a real-world setting.MethodsIn this prospective observational study, physicians adjusted imipenem doses empirically based on renal function and infection severity. Plasma concentrations were quantified via liquid chromatography-mass spectrometry, and pharmacokinetic parameters were calculated. Pharmacokinetic/pharmacodynamic targets were defined as 100% of the dosing interval with free drug concentrations above the minimum inhibitory concentration (MIC) and four times above the MIC, with MICs set at 1, 2, 4, 8, and 16 mg/L.ResultsThe analysis included 20 patients with extended infusion (0.5 g q6h/q8h or 1 g q8h) and 20 with continuous infusion (matched doses). Continuous infusion showed lower trough concentration variability (coefficient of variation: 25.5% vs. 67.3%) and significantly higher area under the curve and minimum plasma concentration values at all doses (p_adj ≤ 0.002). Continuous infusion achieved superior target attainment: for 100% fT > MIC, significant differences were observed at MICs ≥4 mg/L (p = 0.01). For 100% fT > 4× MIC, continuous infusion outperformed extended infusion starting from MICs ≥1 mg/L (p < 0.01), with 3.0 g/day continuous infusion achieving 100% attainment at an MIC of 4 mg/L.ConclusionsContinuous infusion demonstrated superior pharmacokinetic/pharmacodynamic target attainment than extended infusion at equivalent doses, particularly for pathogens with an MIC ≥4 mg/L or cases requiring aggressive targets. Continuous infusion may benefit patients with elevated creatinine clearance, those with infections caused by pathogens with high MIC, and those requiring aggressive pharmacodynamic target attainment.