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Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Therapeutic Drug Monitoring of Antibiotics in Critically Ill Children: An Observational Study in a Pediatric
Noémie de Cacqueray1, Sana Boujaafar2,3, Emmanuelle Bille4
1Department of Pediatric Intensive Care Unit, Necker Enfants Malades Hospital, Université de Paris.
Insights
Therapeutic drug monitoring (TDM) optimizes antibiotic exposure in critically ill children. Timely TDM assays and dose adjustments improve antibiotic levels, crucial for treating pediatric sepsis.
Area of Science:
- Pediatric critical care medicine
- Clinical pharmacology
- Infectious diseases
Background:
- Critically ill children with sepsis often receive inadequate antibiotic exposure.
- Therapeutic drug monitoring (TDM) is essential for optimizing antibiotic therapy in this population.
Purpose of the Study:
- To describe the utilization and impact of TDM for antibiotics in critically ill children.
- To evaluate the effectiveness of TDM in achieving pharmacokinetic/pharmacodynamic targets.
Main Methods:
- A single-center observational study was conducted in a pediatric intensive care unit.
- Clinical and laboratory data were collected, and plasma antibiotic levels were measured.
- Validated analytical methods were used for antibiotic assays.
Main Results:
- TDM was performed in 27.8% of 209 children, with TDM patients exhibiting greater organ dysfunction.
- 46.2% of initial antibiotic concentrations were below target levels.
- Dose adjustments based on TDM increased on-target measurements from 20% to 70%.
Conclusions:
- TDM is effective in optimizing antibiotic exposure for critically ill children.
- Timely plasma antibiotic assays and minimum inhibitory concentration measurements are critical for TDM success.
- Defining patient selection and management protocols for TDM is important.
Background:
Septic critically ill children are at a high risk of inadequate antibiotic exposure, requiring them to undergo therapeutic drug monitoring (TDM). The aim of this study was to describe the use of TDM for antibiotics in critically ill children.
Methods:
The authors conducted a single-center observational study between June and December 2019, with all children treated with antibiotics in a pediatric intensive care unit located in a French university hospital. Standard clinical and laboratory data were recorded. Blood samples were collected for routine laboratory tests, and plasma antibiotic levels were assayed using validated analytical methods.
Results:
A total of 209 children received antibiotics. TDM was performed in 58 patients (27.8%) who had a greater mean organ dysfunction (according to the International Pediatric Sepsis Consensus Conference) (3 versus 1 in the non-TDM group; P < 0.05) and were treated with antibiotics for longer. A total of 208 samples were analyzed. The median [interquartile range] assay turnaround time was 3 (1-5) days, and 48 (46.2%) of the 104 initial antibiotic concentration values were below the pharmacokinetic/pharmacodynamic targets. A total of 34 (46%) of the 74 off-target TDM measurements available before the end of the antibiotic treatment prompted dose adjustment. This dose adjustment increased the proportion of on-target TDM measurements (70% versus 20% without adjustment). Subsequent measurements of the minimum inhibitory concentration showed that the use of the European Committee on Antimicrobial Susceptibility Testing's epidemiological cutoff values led to underestimation of pharmacokinetic/pharmacodynamic target attainment in 10 cases (20%).
Conclusions:
TDM seems to be an effective means of optimizing antibiotic exposure in critically ill children. This requires timely plasma antibiotic assays and minimum inhibitory concentration measurements. It is important to define which patients should undergo TDM and how this monitoring should be managed.
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