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Published on: August 30, 2018
Suboptimal Beta-Lactam Therapy in Critically Ill Children: Risk Factors and Outcome
Tatjana Van Der Heggen1,2,3,4,5,6,7,8, Evelyn Dhont4, Jef Willems4
1Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
Insights
Subtherapeutic beta-lactam antibiotic levels are frequent in critically ill children, linked to kidney function. Higher estimated glomerular filtration rates and no vasopressor use predict lower drug exposure, guiding potential dose adjustments.
Area of Science:
- Pharmacology and Therapeutics
- Pediatric Critical Care Medicine
- Infectious Diseases
Background:
- Critically ill children often experience altered pharmacokinetics, potentially leading to subtherapeutic beta-lactam antibiotic concentrations with standard dosing.
- Identifying children at risk for suboptimal antibiotic exposure and understanding the impact on outcomes is crucial for effective treatment.
Purpose of the Study:
- To determine the attainment of therapeutic targets for beta-lactam antibiotics in critically ill children.
- To identify risk factors associated with suboptimal antibiotic exposure.
- To investigate the relationship between non-attainment of therapeutic targets and clinical outcomes.
Main Methods:
- A post hoc analysis of the 'Antibiotic Dosing in Pediatric Intensive Care' study.
- Measurement of steady-state trough plasma concentrations for beta-lactam antibiotics (amoxicillin-clavulanic acid, piperacillin-tazobactam, meropenem).
- Logistic regression analysis to identify factors associated with subtherapeutic concentrations and clinical outcomes.
Main Results:
- High rates of subtherapeutic concentrations were observed: 65% for amoxicillin-clavulanic acid, 90% for piperacillin-tazobactam, and 71% for meropenem.
- Estimated glomerular filtration rate (eGFR) and the absence of vasopressor treatment were independently associated with target non-attainment.
- No significant association was found between antibiotic concentrations and clinical failure.
Conclusions:
- Subtherapeutic beta-lactam concentrations are common in critically ill children and are associated with renal function.
- eGFR estimations may aid in identifying patients needing higher antibiotic doses.
- Further research is warranted to explore the clinical impact of subtherapeutic antibiotic concentrations.
Objectives:
In critically ill children, severely altered pharmacokinetics may result in subtherapeutic β-lactam antibiotic concentrations when standard pediatric dosing regimens are applied. However, it remains unclear how to recognize patients most at risk for suboptimal exposure and their outcome. This study aimed to: 1) describe target attainment for β-lactam antibiotics in critically ill children, 2) identify risk factors for suboptimal exposure, and 3) study the association between target nonattainment and clinical outcome.
Design:
Post hoc analysis of the "Antibiotic Dosing in Pediatric Intensive Care" study (NCT02456974, 2012-2019). Steady-state trough plasma concentrations were classified as therapeutic if greater than or equal to the minimum inhibitory concentration of the (suspected) pathogen. Factors associated with subtherapeutic concentrations and clinical outcome were identified by logistic regression analysis.
Setting:
The pediatric and cardiac surgery ICU of a Belgian tertiary-care hospital.
Patients:
One hundred fifty-seven patients (aged 1 mo to 15 yr) treated intravenously with amoxicillin-clavulanic acid, piperacillin-tazobactam, or meropenem.
Interventions:
None.
Measurements And Main Results:
Three hundred eighty-two trough concentrations were obtained from 157 patients (median age, 1.25 yr; interquartile range, 0.4-4.2 yr). Subtherapeutic concentrations were measured in 39 of 60 (65%), 43 of 48 (90%), and 35 of 49 (71%) of patients treated with amoxicillin-clavulanic acid, piperacillin-tazobactam, and meropenem, respectively. Estimates of glomerular filtration rate (eGFR; 54% increase in odds for each sd increase in value, 95% CI, 0.287-0.736; p = 0.001) and the absence of vasopressor treatment (2.8-fold greater odds, 95% CI, 1.079-7.253; p = 0.034) were independently associated with target nonattainment. We failed to identify an association between antibiotic concentrations and clinical failure.
Conclusions:
Subtherapeutic β-lactam concentrations are common in critically ill children and correlate with renal function. eGFR equations may be helpful in identifying patients who may require higher dosing. Future studies should focus on the impact of subtherapeutic concentrations on clinical outcome.
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