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Publication
β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity
Advisor(s)
Abstract(s)
Antimicrobial prescription in critically ill patients represents a complex challenge due to the
difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics
and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a
worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable
pharmacokinetics. In critically ill patients, interindividual and intraindividual real-time -lactam
antibiotic dose adjustments according to the patient’s condition are critical. The continuous infusion
of -lactams and the therapeutic monitoring of their concentration have both been proposed to
improve their efficacy, but strong data to support their use are still lacking. The knowledge of the
pharmacokinetic/pharmacodynamic targets is poor and is mostly based on observational data. In
patients with renal or hepatic failure, selecting the right dose is even more tricky due to changes in
drug clearance, distribution, and the use of extracorporeal circuits. Intermittent usage may further
increase the dosing conundrum. Recent data have emerged linking overexposure to -lactams to
central nervous system toxicity, mitochondrial recovery delay, and microbiome changes. In addition,
it is well recognized that -lactam exposure facilitates resistance selection and that correct dosing can
help to overcome it. In this review, we discuss recent data regarding real-time -lactam antibiotic dose
adjustment, options in special populations, and the impacts on mitochondria and the microbiome.
Description
Keywords
b-lactam pharmacokinetics pharmacodynamics critical care dosing organ failure toxicity resistance