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Cefoxitin Prophylaxis During Pediatric Cardiac Surgery: Retrospective Exploration of Postoperative Trough Levels
Zaccaria Ricci1, Simona Benegni1, Jeffrey J Cies2,3,4
1From the Department of Cardiology and Cardiac Surgery, Pediatric Cardiac Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Insights
Cefoxitin levels vary widely in children post-cardiac surgery. Serum creatinine and weight impact drug concentration, with most patients not reaching therapeutic cefoxitin targets.
Area of Science:
- Pharmacology
- Pediatric Critical Care
- Antibiotic Therapy
Background:
- Cefoxitin is a key antibiotic used in pediatric cardiac surgery.
- Understanding cefoxitin concentration variability is crucial for effective treatment.
- Inter-individual variability in drug levels can impact patient outcomes.
Purpose of the Study:
- To investigate cefoxitin trough level variability in pediatric cardiac surgery patients.
- To identify predictors of serum cefoxitin concentration.
- To determine the probability of achieving target drug levels.
Main Methods:
- Retrospective analysis of children undergoing elective cardiac surgery.
- Inclusion of patients with cefoxitin trough levels measured up to 24 hours post-surgery.
- Statistical analysis to identify relationships between patient factors and drug concentrations.
Main Results:
- Significant variability (150-340 fold) in free cefoxitin concentrations was observed.
- Pharmacodynamic (PD) targets were achieved in only 28% (Staphylococcus Aureus) and 16% (E. coli) of patients.
- Patient weight and serum creatinine levels were significant predictors of PD target attainment.
Conclusions:
- Cefoxitin trough concentrations exhibit significant variability within 24 hours post-pediatric cardiac surgery.
- Serum creatinine and body weight are independent predictors of cefoxitin concentration.
- The majority of patients did not achieve therapeutic cefoxitin levels, irrespective of the target bacteria.
Background:
This study aimed to explore inter-individual variability of cefoxitin trough levels, predictors of serum cefoxitin concentration and the probability of target attainment of drug levels above 4 mg/L after pediatric cardiac surgery.
Methods:
Retrospective study on children scheduled for elective cardiac surgery and having cefoxitin trough levels available up to 24 hours postsurgery.
Results:
Overall, 68 children (9 neonates, 34 infants, 15 children below or equal to 10 years old and 10 patients above this age) were included. Of these, 16 surgeries were performed off cardiopulmonary bypass and 52 were performed on cardiopulmonary bypass. The free cefoxitin concentrations showed a median (interquartile range) concentration of 1.7 (0.6-4.2) mg/L. The range of cefoxitin concentrations showed a 150-fold and 340-fold variability at cardiac intensive care unit admission and after 24 hours, respectively. The pharmacodynamics (PD) targets of free cefoxitin at 100% of the dosing interval, considering Eucast breakpoints for Methicillin Sensitive Staphylococcus Aureus (4 mg/L) and E.Coli (8 mg/L), were obtained in 28% and 16% of patients, respectively. Patient weight (odds ratio, 0.7; 95% confidence interval, 0.62-0.92; P = 0.006) and serum creatinine concentrations (odds ratio, 25; 95% confidence interval, 18-36; P = 0.004) showed a significant relationship with the PD targets.
Conclusions:
Cefoxitin trough concentrations vary significantly in the first 24 hours after pediatric cardiac surgery. Both serum creatinine and body weight showed independent associations with cefoxitin concentration. The PD target was not obtained in the vast majority of the explored population, regardless of the target bacteria.
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