Pharmacokinetics of the Meropenem Component of Meropenem‐Vaborbactam in the Treatment of KPC‐Producing Klebsiella pneumoniae Bloodstream Infection in a Pediatric Patient

Abstract

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.

Ultra-performance liquid chromatography-tandem mass spectrometric method for quantitation of the recently Food and Drug Administration approved combination of vaborbactam and meropenem in human plasma

“…It is first-in-class boronic acid-based β-lactamase inhibitor and a carbapenem combination product. This combination has been introduced for treatment of complicated urinary tract infections [ 1 ]. VBR is chemically designated as 2-[(3R,6S)-2-hydroxy-3-[(2-thiophen-2 yl-acetyl)amino]oxaborinan-6-yl]acetic acid.…”

New β-Lactam–β-Lactamase Inhibitor Combinations

“…The patient received this therapy as monotherapy for 14 days with no evidence of treatment emergent adverse events and with good clinical outcome and clearance of bacteremia. The pharmacodynamic target of time above MIC of Ն40% was achieved for 100% of the dosing interval (191).…”

“…A single case report described a 4-year-old child with KPC-producing K. pneumoniae bacteremia treated with MER-VAB at a dose of 40 mg/kg every 6 h infused over 3 h (191). The patient received this therapy as monotherapy for 14 days with no evidence of treatment emergent adverse events and with good clinical outcome and clearance of bacteremia.…”

Neonatal multidrug-resistant gram-negative infection: epidemiology, mechanisms of resistance, and management

“…Pediatric data are limited to case reports. ( 139 ) Imipenem-cilastatin-relebactam is a β-lactam/β-lactamase inhibitor with activity against KPC-producing CRE, but not metallo-β-lactamase-producing isolates. ( 140 , 141 ) It was approved for use in patients 18 and over by the FDA in 2019.…”