Prolonged cefepime infusion reached target more often than intermittent dosing against higher-MIC bacteria in children

Design

Prospective observational pharmacokinetic study, two PICUs

Population

75 critically ill children, 78 cefepime courses (19 prolonged, 59 intermittent)

Primary outcome

Attainment of 100% fT >4×MIC

Effect

Optimal exposure 53% vs 59% (p = 0.79); higher target attainment with prolonged infusion for MIC ≥1 mg/L (p < 0.05)

This prospective observational study in two paediatric intensive care units included 75 critically ill children (78 cefepime courses): 19 received prolonged infusion and 59 intermittent infusion. Free drug concentrations were estimated by Bayesian forecasting, with a target of concentrations above four times the MIC for the whole dosing interval.

Optimal exposure was similar (53% vs 59%). Overexposure tended to be more common with prolonged infusion (42% vs 27%) and underexposure less common (5% vs 14%), though neither difference was significant. For MICs of 1 mg/L or higher, the probability of target attainment was significantly better with prolonged infusion.

The mechanism is time-dependent killing: beta-lactams work while concentrations stay above the MIC, so spreading the dose over longer infusions helps against less susceptible organisms. Overexposure matters because cefepime neurotoxicity is well described, especially with renal impairment.

• Consider prolonged cefepime infusion in critically ill children when the pathogen MIC is 1 mg/L or higher.
• Where available, use therapeutic drug monitoring to guide beta-lactam dosing in the ICU.
• Watch for cefepime neurotoxicity (encephalopathy, myoclonus, non-convulsive seizures), particularly with renal impairment.
• Adjust dose for kidney function, and reassess if it changes.

Why it matters

Rising MICs in Indian ICUs make the way a beta-lactam is infused as important as the dose.

Don't overread it

This was a small observational study; it did not measure clinical cure or mortality.

The statistics, in plain English

With only 19 prolonged infusions, the study could not show significant differences in over- or underexposure; the target attainment benefit applied at higher MICs. Groups were not randomised, so sicker children may have been given one method more than the other.

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