Pharmacokinetics of meropenem during intermittent and continuous intravenous application in patients treated by continuous renal replacement therapy.
OBJECTIVE
The clinical effect of beta-lactam antibiotics depends on the time of drug concentration above the minimal inhibitory concentration (MIC) for a susceptible bacterium. Continuous infusion (CI) of beta-lactams such as meropenem may therefore be a more rational approach than intermittent bolus injections (IB). The aim of this study was to test whether CI of meropenem achieves effective drug concentrations comparable to IB in patients treated by continuous renal replacement therapy (CRRT).


METHODS
Prospective, randomised cross-over study.


METHODS
Twelve-bed medical intensive care unit (ICU).


METHODS
Six ICU patients were randomised to receive either meropenem 1 g IB every 12 h or a 0.5 g i.v. loading dose followed by 2 g i.v. CI over 24 h. After 2 days, regimens were crossed over. Meropenem pharmacokinetics were determined on days 2 and 4.


RESULTS
Peak serum concentration [median (25% and 75% quartiles)] after short infusion of 1 g meropenem were 62.8 (51.4; 85.0) mg/l, trough levels at 12 h were 8.1 (4.5; 18.7) mg/l, and serum half-life was 5.3 (5.1; 7.0) h. Steady-state concentrations during CI were 18.6 (13.3; 24.5) mg/l. The AUCs during either treatment were comparable and determined as 233 (202; 254) mg/l*h (IB) and 227 (182; 283) mg/l*h (CI), respectively. Four hours after IB, drug concentrations dropped below CI steady-state concentrations.


CONCLUSIONS
Appropriate antibacterial concentrations of meropenem in patients with CRRT are easily achievable with CI. CI may be an effective alternative dosing regimen to IB. A prospective comparison of the clinical efficacy of the two dosage regimens is warranted.
Langgartner
Julia
J
Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. julia.langgartner@klinik.uni-regensburg.de
Vasold
Antje
A
Glück
Thomas
T
Reng
Michel
M
Kees
Frieder
F
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D016018:Least-Squares Analysis; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D017582:Renal Replacement Therapy; D013845:Thienamycins / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem