Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis
JAMA, 2024 · International, open-label randomized clinical trial in 104 ICUs (n=7,031 in the primary analysis).
Clinical question
In critically ill adults with sepsis receiving piperacillin-tazobactam or meropenem, does continuous infusion improve 90-day survival compared with intermittent infusion?
What the trial found
Continuous infusion did not significantly reduce the prespecified primary 90-day mortality endpoint, although clinical cure was higher and the mortality point estimate favored continuous infusion.
Current guideline position
Use optimized β-lactam dosing based on drug, organism/MIC, renal replacement modality, severity, and local protocol; do not claim a definitive mortality advantage for continuous infusion.
Clinical interpretation
Supports prolonged/continuous β-lactam administration as a pharmacokinetically rational option in selected critically ill patients, but it should not be taught as proven to reduce mortality.
Life-threatening organ dysfunction caused by a dysregulated host response to infection — recognized by an acute rise in SOFA score, not by infection plus fever alone.
The subset of sepsis with profound circulatory and cellular/metabolic abnormality — clinically identified by a vasopressor requirement to maintain MAP ≥ 65 mmHg plus lactate > 2 mmol/L despite adequate fluid resuscitation.
Molecular resistance mechanisms (ESBL, AmpC, KPC, NDM, OXA-48, DTR-Pseudomonas, CRAB), the MERINO trial, and modern novel beta-lactamase inhibitor therapeutics.