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Updated: Dec 17, 2025
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Are β-lactam concentrations adequate in severe sepsis and septic shock in children?
Anais Chosidow1, Sihem Benaboud2, Agathe Beranger3
1Armand-Trousseau hospital, AP-HP, pediatric department, 26, avenue du Dr-Arnold-Netter, 75012 Paris, France.
Insights
Antibiotic dosing for pediatric severe sepsis may be insufficient. Many critically ill children had suboptimal beta-lactam concentrations, linked to early treatment and higher creatinine clearance.
Area of Science:
- Pediatric critical care medicine
- Pharmacokinetics and pharmacodynamics
- Infectious diseases
Background:
- Severe sepsis and septic shock treatment relies on timely antibiotic administration.
- Achieving adequate drug concentrations is crucial for effective treatment in critically ill children.
Purpose of the Study:
- To determine plasma concentrations of commonly used beta-lactam antibiotics in critically ill children with severe sepsis or septic shock.
- To assess the rate of patients with suboptimal antibiotic exposure.
- To identify clinical and biological factors associated with suboptimal drug levels.
Main Methods:
- Prospective study of children (<18 years) with severe sepsis/septic shock from January 2016 to May 2017.
- Collection of plasma samples from pediatric intensive care unit patients.
- Analysis of beta-lactam concentrations using high-performance liquid chromatography.
Main Results:
- 64.9% of 37 patients exhibited insufficient beta-lactam concentrations.
- High rates of suboptimal levels were observed for piperacillin-tazobactam (77%), amoxicillin (86%), and meropenem (50%).
- Insufficient concentrations were associated with early measurements (<72 hours from sepsis onset) and increased creatinine clearance.
Conclusions:
- Current beta-lactam dosing regimens may be suboptimal in critically ill septic children.
- Further research is needed to optimize antibiotic dosing strategies in this population.
- Pharmacokinetic variability impacts antibiotic efficacy in pediatric sepsis.
Aim Of The Study:
Early administration of appropriate antibiotic therapy with adequate concentration is the cornerstone of the severe sepsis and septic shock's treatment. We aim to describe the plasma concentration of the most used β-lactams in critically ill children, to describe the rate of patients with suboptimal exposure, and associated clinical and biological factors.
Methods:
From January 2016 to May 2017, children less than 18 years old with severe sepsis or septic shock were included. Samples were collected in pediatric intensive care unit for children with severe sepsis or septic shock. β-lactam plasma concentrations were analysed using high performance liquid chromatography.
Results:
Among the 37 enrolled patients, 24 (64.9%) had insufficient concentration [cefotaxime 7/14 (43%); piperacillin-tazobactam, 10/13 (77%); amoxicillin 6/7 (86%); meropenem 3/6 (50%), cefazolin 1/4 (25%), imipenem 0/2 (0%); ceftazidime 0/1 (0%)]. Insufficient concentrations were associated with early measurements [<72hours from the sepsis' onset (P=0.035) and an increased creatinine clearance (P=0.01)].
Conclusion:
β-lactams current dosing in critically ill septic children could be suboptimal.
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