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Pharmacokinetics of meropenem during intermittent and continuous intravenous application in patients treated by
Julia Langgartner1, Antje Vasold, Thomas Glück
1Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. julia.langgartner@klinik.uni-regensburg.de
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).
Design:
Prospective, randomised cross-over study.
Setting:
Twelve-bed medical intensive care unit (ICU).
Patients And Interventions:
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.
Measurements And 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.
Conclusion:
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.
Insights
Continuous infusion (CI) of meropenem provides effective drug concentrations in patients undergoing continuous renal replacement therapy (CRRT), comparable to intermittent bolus injections (IB). This suggests CI is a viable alternative for meropenem dosing in CRRT patients.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Critical Care Medicine
- Infectious Diseases
Background:
- The efficacy of beta-lactam antibiotics, including meropenem, is linked to maintaining drug concentrations above the minimal inhibitory concentration (MIC).
- Continuous infusion (CI) may offer a more rational dosing strategy for beta-lactams compared to intermittent bolus injections (IB).
- Patients on continuous renal replacement therapy (CRRT) present unique challenges for antibiotic dosing due to altered drug clearance.
Purpose of the Study:
- To evaluate if continuous infusion (CI) of meropenem achieves effective drug concentrations comparable to intermittent bolus injections (IB).
- To assess meropenem pharmacokinetics in patients receiving CRRT.
- To determine the suitability of CI as an alternative meropenem dosing regimen in CRRT patients.
Main Methods:
- Prospective, randomized cross-over study conducted in a medical intensive care unit (ICU).
- Six ICU patients received meropenem via IB (1 g every 12 h) and CI (0.5 g loading dose followed by 2 g over 24 h) in a cross-over design.
- Meropenem pharmacokinetics, including serum concentrations and area under the curve (AUC), were measured on days 2 and 4.
Main Results:
- Peak serum concentrations after IB were 62.8 mg/l, with trough levels at 12 h of 8.1 mg/l.
- Steady-state concentrations during CI were 18.6 mg/l.
- AUCs were comparable between IB (233 mg/l*h) and CI (227 mg/l*h); however, meropenem concentrations dropped below CI steady-state levels within 4 hours after IB.
Conclusions:
- Continuous infusion of meropenem easily achieves appropriate antibacterial concentrations in patients undergoing CRRT.
- CI represents an effective alternative dosing regimen to IB for meropenem in this patient population.
- Further prospective studies comparing the clinical efficacy of CI versus IB meropenem dosing are warranted.
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