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

In Japan, the approved maximum daily dose of cefepime (4 g) is lower than international standards (6 g), potentially compromising efficacy against <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) 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% <i>f</i>T > 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.