Abstract
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 ss-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 ...
Abstract
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 ss-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 2g i.v. CI over 24h. 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.
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