Global Health & Medicine 2025;7(6):449-453.

Optimization of cefepime dosage regimens for Pseudomonas aeruginosa infections in Japanese patients based on a pharmacokinetic/ pharmacodynamic analysis considering efficacy and safety: Is a 6 g daily dose and continuous infusion necessary?

Ebihara F, Maruyama T, Kasai H, Shiokawa M, Matsunaga N, Hamada Y

In Japan, the approved maximum daily dose of cefepime (4 g) is lower than international standards (6 g), potentially compromising efficacy against Pseudomonas aeruginosa (P. aeruginosa) infections. Using Monte Carlo simulations with a population pharmacokinetic model for Japanese patients, we determined optimal dosing regimens across renal function levels. The target was 60% fT > MIC (percentage of time free drug concentration exceeds minimum inhibitory concentration), with ≥ 90% probability of target attainment for minimum inhibitory concentration (MIC) up to 8 mg/L. Lower doses sufficed for impaired renal function, while higher doses with prolonged infusion (2 g q8 (3 h)) were needed for creatinine clearance (CCr) 101–130 mL/min. For augmented renal clearance (CCr > 130 mL/ min), continuous infusion (2 g loading dose followed by 4 g continuous infusion) achieved optimal attainment below neurotoxicity thresholds. Current approved dosing in Japan may be insufficient; adjustments including prolonged or continuous infusions are crucial for optimizing therapy.

DOI: 10.35772/ghm.2025.01104

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