Ensuring Sufficient Trough Plasma Concentrations for Broad-Spectrum Beta-Lactam Antibiotics in Children With Malignancies: Beware of Augmented Renal Clearance!

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State: Public
Version: author
License: CC BY 4.0
Serval ID
serval:BIB_B465A6064AF2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Ensuring Sufficient Trough Plasma Concentrations for Broad-Spectrum Beta-Lactam Antibiotics in Children With Malignancies: Beware of Augmented Renal Clearance!
Journal
Frontiers in pediatrics
Author(s)
André P., Diezi L., Dao K., Crisinel P.A., Rothuizen L.E., Chtioui H., Decosterd L.A., Diezi M., Asner S., Buclin T.
ISSN
2296-2360 (Print)
ISSN-L
2296-2360
Publication state
Published
Issued date
2021
Peer-reviewed
Oui
Volume
9
Pages
768438
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Introduction: Broad-spectrum beta-lactams are commonly prescribed for empirical or selective treatment of bacterial infections in children with malignancies. In the immunocompromised, appropriate concentration exposure is crucial to ensure antimicrobial efficacy. Augmented renal clearance (ARC) is increasingly recognized in this population, and raises concern for unmet concentration targets. We conducted a retrospective evaluation of meropenem and piperacillin exposure in our hospital's pediatric hematology-oncology patients. Materials and Methods: We compared trough levels of meropenem and piperacillin in a cohort of unselected pediatric hematology-oncology patients stratified based on their estimated renal function as decreased, normal or with ARC, and on their neutrophil count. Results: Thirty-two children provided a total of 51 meropenem and 76 piperacillin samples. On standard intermittent intravenous regimen, 67% of all trough plasma concentrations were below targeted concentrations. In neutropenic children with bacterial infection, all meropenem and 60% of piperacillin levels were below target. Nearly two-thirds of total samples came from children with ARC. In these patients, antimicrobial exposure was insufficient in 85% of cases (compared to 36% in the decreased or normal renal function groups), despite a dosage sometimes exceeding the maximum recommended daily dose. Under continuous infusion of piperacillin, only 8% of plasma levels were insufficient. Discussion: Intermittent administration of meropenem and piperacillin often fails to ensure sufficient concentration exposure in children treated for malignancies, even at maximal recommended daily dosage. This can in part be attributed to ARC. We recommend thorough assessment of renal function, resolute dosage adjustment, continuous infusion whenever possible and systematic therapeutic drug monitoring.
Keywords
Pediatrics, Perinatology and Child Health, augmented renal clearance, beta-lactams, cancer, child, kidney function tests, meropenem, neoplasms, piperacillin
Pubmed
Web of science
Open Access
Yes
Create date
13/01/2022 13:30
Last modification date
26/04/2022 6:37
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