Meropenem is used as a continuous infusion (not bolus) in critically ill patients with Pseudomonas bacteremia. The pharmacodynamic rationale is:

• A Meropenem exhibits concentration-dependent killing; continuous infusion maximizes Cmax/MIC ratio, enhancing bactericidal activity
• B Meropenem exhibits time-dependent killing; continuous infusion maximizes the time plasma concentrations exceed the MIC (%T>MIC target: 40–100%), improving efficacy against organisms with elevated MICs ✓
• C Continuous infusion prevents renal tubular secretion of meropenem, increasing plasma levels and bioavailability
• D Continuous infusion avoids peak concentrations that activate meropenem autoinduction and accelerated hydrolysis by renal DHP-I

Explanation

Carbapenems, like all beta-lactams, exhibit time-dependent (not concentration-dependent) bactericidal activity. The PK/PD index predictive of clinical efficacy is %T>MIC — the percentage of the dosing interval that free drug concentration exceeds the MIC. The bactericidal effect is maximal when T>MIC is 40–100% of the dosing interval for carbapenems (depending on organism). Against Pseudomonas aeruginosa with elevated MICs (e.g., MIC 4–8 mg/L), intermittent bolus dosing may not maintain T>MIC for adequate time, whereas continuous infusion (achieving steady-state concentration = target MIC level throughout 24 hours) maintains 100% T>MIC. This strategy is supported by Monte Carlo PK/PD simulation and clinical PK studies in ICU patients with augmented renal clearance.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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