Continuous vs bolus administration of imipenem in critically ill patients with ICU-acquired pneumonia
© BioMed Central Ltd. 2004
Published: 15 March 2004
Background and goal of study
Most recently, administration modus for β-lactam antibiotics has become a matter of debate, and continuous infusion has been suggested . We studied whether plasma concentrations of imipenem were sufficiently maintained using a loading dose and continuous infusion regimen, and that this regimen would be superior to a higher amount of drug given by the standard intermittent bolus regimen.
Patients and methods
We randomized 20 critically ill patients with ICU-acquired pneumonia to receive imipenem either 2 g/24 hours by continuous infusion (CON, n = 10) or bolus dosing (1 g every 8 hours) (BOL, n = 10). In both groups, a loading dose of 1 g imipenem was administered, which was followed by continuous infusion or further bolus treatment 4 hours after loading. Plasma imipenem concentrations were measured at baseline, 4, 10, 16, 22, 46 and 70 hours. Arterial blood samples were taken immediately prior to begin of the continuous regimen and before each respective bolus administration. Patients' age (62 ± 16 vs 59 ± 16 years), SAPS II score (43 ± 12 vs 44 ± 14) and renal function (creatinine clearance, 128 ± 35 vs 122 ± 33 ml/min) were comparable between both groups.
Results and discussion
After 4 and 10 hours, plasma imipenem concentrations were similar in both groups. However, mean imipenem plasma trough concentrations at the following time points (16, 22, 46, and 70 hours) were significantly higher in CON than BOL. For comparison, at 16, 22, 46 and 70 hours, all patients in CON had concentrations > 2 μg/ml (50% minimum inhibitory concentration for Pseudomonas aeruginosa), while this was only achieved in three of 10 patients in BOL. These data suggest that continuous infusion is advantageous and its benefit should therefore be investigated in clinical outcome studies.
Continuous imipenem infusion administered as 2 g over 24 hours guarantees more sufficient plasma concentrations when compared with a standard regimen (1 g every 8 hours) that is associated with insufficient trough concentrations.