Overall, 95% of patients had subtherapeutic anti-infective concentrations and did not achieve the requisite pharmacodynamic exposure with current pediatric dosing recommendations. All patients achieved a microbiological response, and 95.7% achieved clinical response with active β-lactam therapeutic drug management. These data suggest β-lactam therapeutic drug management is a potentially valuable intervention to optimize anti-infective pharmacokinetics and the pharmacodynamic exposure. Further, these data also suggest the need for additional research in specific pediatric populations and assessing clinical outcomes associated with β-lactam therapeutic drug management in a larger cohort of pediatric patients.
These data suggest the reference dosage regimens for meropenem (20-40 mg/kg per dose every 8 hours) do not meet an appropriate pharmacodynamic target attainment in critically ill children ages 1 to 9 years. Based on these data, only the 3- to 4-hour prolonged infusion and 24-hour continuous infusion regimens were able to achieve an optimal probability of target attainment against all susceptible Gram-negative bacteria in critically ill children for 40% T> MIC. Dosage regimens of 120 and 160 mg/kg/day as continuous infusion regimens may be necessary to achieve an optimal probability of target attainment against all susceptible Gram-negative bacteria in critically ill children for 80% T> MIC. Based on these findings, confirmation with a larger, prospective investigation in critically ill children is warranted.
These data suggest the pharmacokinetics of ceftaroline in PICU patients is different than healthy pediatric and adult patients, most notably a faster clearance and larger volume of distribution. A higher mg/kg dose and a more frequent dosing interval for ceftaroline may be needed in PICU patients to provide appropriate pharmacodynamic exposures. Larger pharmacokinetic, pharmacodynamic, and interventional treatment trials in the PICU population are warranted.
Meropenem‐vaborbactam is a new β‐lactam/β‐lactamase inhibitor combination designed to target Klebsiella pneumoniae carbapenemase (KPC)‐producing Enterobacteriaceae. Meropenem‐vaborbactam was United States Food and Drug Administration–approved for complicated urinary tract infections in patients 18 years of age or older. An understanding of the pharmacokinetics of meropenem when given in combination with vaborbactam is important to understanding the dosing of meropenem‐vaborbactam. In addition, the safety and efficacy of meropenem‐vaborbactam in a pediatric patient have yet to be described in the literature. The authors conducted a retrospective single‐patient chart review for a 4‐year‐old male patient with short bowel syndrome, colostomy and gastrojejunal tube, bronchopulmonary dysplasia, and a central line for chronic total parenteral nutrition and hydration management, complicated with multiple central line–associated bloodstream infections (BSIs). The patient was brought to our medical center with fever concerning for a BSI. On day 2, the patient was started on meropenem‐vaborbactam at a dosage of 40 mg/kg every 6 hours infused over 3 hours for KPC‐producing K. pneumoniae BSI. Meropenem serum concentrations obtained on day 5 of meropenem‐vaborbactam therapy, immediately following the completion of the infusion and 1 hour after the infusion, were 51.3 and 13.6 μg/ml, respectively. Serum concentrations correlated to a volume of distribution of 0.59 L/kg and a clearance of 13.1 ml/min/kg. Repeat blood cultures remained negative, and meropenem‐vaborbactam was continued for a total of 14 days. A meropenem‐vaborbactam regimen of 40 mg/kg every 6 hours given over 3 hours was successful in providing a target attainment of 100% for meropenem serum concentrations above the minimum inhibitory concentration for at least 40% of the dosing interval and was associated with successful bacteremia clearance in a pediatric patient.
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