Imipenem levels are not predictable in the critically ill patient.
BACKGROUND
Critically ill patients often demonstrate extremely unusual volumes of distribution (Vd) and half-lives (t1/2) of drugs. Imipenem is a widely used antibiotic in critically ill patients.


METHODS
We performed high-performance liquid chromatography analysis of imipenem in samples from 50 critically ill patients treated with either 500 or 1,000 mg.


RESULTS
Peak imipenem levels varied from 1.56 microg/mL to 58.8 microg/mL. Trough levels varied between 0.0 microg/mL and 15.62 microg/mL. Only 54% of patients maintained a trough level greater than 4 microg/mL. Both the Vd and the t1/2 of imipenem were much greater than observed in other patient populations.


CONCLUSIONS
The pharmacokinetic activity of imipenem in critically ill patients is different from that in other patient populations. There is a very weak correlation between dosage and serum concentrations. Therapeutic failures of imipenem may be because of unpredictable pharmacodynamics (Vd and t1/2) in critically ill surgical patients.
Belzberg
Howard
H
Department of Surgery, Los Angeles County and University of Southern California Medical Center, 90033, USA. belzberg@usc.edu
Zhu
Jay
J
Cornwell
Edward E
EE
Murray
James A
JA
Sava
Jack
J
Salim
Ali
A
Velmahos
George C
GC
Gill
Mark A
MA
D018806:APACHE; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D001794:Blood Pressure; D002851:Chromatography, High Pressure Liquid; D003422:Critical Care / Q000379:methods; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D015378:Imipenem / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014949:Wounds, Nonpenetrating / Q000378:metabolism
D000900:Anti-Bacterial Agents; D015378:Imipenem