Background and methods: Imipenem is a broad-spectrum antibiotic used mainly for serious infections in critically ill patients. Because the infection originates mostly from a certain tissue, we assessed tissue concentrations of imipenem using microdialysis in patients in intensive care with serious infections compared with healthy volunteers. Most patients were >60 years old and had renal failure; most patients also had impaired liver, heart, or lung function.
Results: Muscle and subcutaneous tissue concentrations in patients (maximum of 2.3 +/- 1.5 microg/mL for both muscle and subcutaneous tissue) were significantly lower than those in healthy subjects (maximum of 12.8 +/- 1.6 and 10.7 +/- 1.0 microg/mL for muscle and subcutaneous tissue). The tissue distribution rate constants for muscle and subcutaneous tissue were also significantly lower in patients (1.95 +/- 0.6 and 1.1 +/- 0.2 h(-l), respectively) than in healthy subjects (5.2 +/- 1.0 and 6.6 +/- 1.7 h(-1), respectively), meaning that tissue distribution in patients was reduced and retarded. Values for area under the plasma concentration-time curve did not significantly differ between patients and healthy subjects (37.4 +/- 5.9 microg. h/mL and 46.0 +/- 4.4 microg. h/mL, respectively,) although the elimination of imipenem in patients was prolonged (clearance, 6.3 +/- 0.8 L/h and 13.2 +/- 1.4 L/h in patients and healthy subjects, respectively).
Conclusions: Our data suggest that the amount and velocity of imipenem tissue distribution in seriously ill patients is reduced compared with those values in healthy volunteers. Dose adjustments that are exclusively based on plasma concentration data may therefore be misleading and may result in potential underdosing.