β-lactam dosing strategies: Think before you push.

Area of Science:

• Pharmacology
• Infectious Diseases
• Clinical Pharmacy

Background:

• Cefepime, a broad-spectrum β-lactam antibiotic, is crucial for treating serious infections.
• Intravenous push (IVP) administration of cefepime is being explored to improve efficiency and reduce costs.
• Potential impacts of IVP cefepime on antibiotic exposure and pharmacodynamic efficacy require thorough evaluation.

Purpose of the Study:

• To compare the pharmacodynamic (PD) effect of cefepime administered via IVP versus 30-minute intermittent infusion.
• To evaluate the probability of target attainment (PTA) for cefepime regimens across various renal functions and minimum inhibitory concentrations (MICs).

Main Methods:

• Population pharmacokinetic modeling of cefepime was employed.
• Simulations were conducted for IVP and 30-minute intermittent infusion regimens.
• The primary endpoint was the absolute difference in PTA, defined as free drug concentrations exceeding MIC for ≥70% of the dosing interval.

Main Results:

• IVP cefepime demonstrated lower PTA compared to intermittent infusion, particularly at elevated MICs (1-4 mg/L and ≥8 mg/L).
• Absolute PTA differences ranged up to 5.4% at MICs of 1-4 mg/L.
• Higher renal function was associated with lower PTAs across simulated regimens.

Conclusions:

• Simulated cefepime IVP resulted in reduced PTA at higher MICs compared to intermittent infusion.
• Clinicians should exercise caution with IVP cefepime due to potential unintended clinical consequences.
• Further evaluation is needed to optimize cefepime dosing strategies.