Therapeutic drug monitoring of liposomal amphotericin B in children. Are we there yet? A systematic review
© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy..
INTRODUCTION: Therapeutic drug monitoring (TDM) is a tool that supports personalized dosing, but its role for liposomal amphotericin B (L-amb) is unclear. This systematic review assessed the evidence for L-amb TDM in children.
OBJECTIVES: To evaluate the concentration-efficacy relationship, concentration-toxicity relationship and pharmacokinetic/pharmacodynamic (PK/PD) variability of L-amb in children.
METHODS: We systematically reviewed PubMed and Embase databases following PRISMA guidelines. Eligible studies included L-amb PK/PD studies in children aged 0-18 years. Review articles, case series of <five patients, editorials and animal studies were excluded. Quality assessment was performed using the Critical Appraisal of Clinical Pharmacokinetics tool. The concentration-efficacy and concentration-toxicity relationships and PK/PD variability were analysed.
RESULTS: In total, 4220 studies were screened; 6 were included, presenting data on 195 children. Invasive candidiasis and aspergillosis were the two most common infections treated with L-amb. Studies showed significant PK variability due to age (mean age ranged from 14 days to 17 years), body weight, non-linear PK and changes in the volume of distribution. Limited evidence supported a peak concentration/MIC (Cmax/MIC) of 25-50 for optimal efficacy and an AUC24 of >600 mg·h/L for nephrotoxicity. L-amb doses of 2.5-10 mg/kg/day were reported to achieve Cmax/MIC > 25 using an MIC of 1 mg/L.
CONCLUSIONS: While significant PK variability was observed in children, evidence to support routine L-amb TDM was limited. Further studies on efficacy and toxicity benefits are required before routine TDM of L-amb can be recommended.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:79 |
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| Enthalten in: |
The Journal of antimicrobial chemotherapy - 79(2024), 4 vom: 02. Apr., Seite 703-711 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lai, Tony [VerfasserIn] |
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| Links: |
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| Themen: |
7XU7A7DROE |
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| Anmerkungen: |
Date Completed 03.04.2024 Date Revised 04.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/jac/dkae003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367434075 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. | ||
| 520 | |a INTRODUCTION: Therapeutic drug monitoring (TDM) is a tool that supports personalized dosing, but its role for liposomal amphotericin B (L-amb) is unclear. This systematic review assessed the evidence for L-amb TDM in children | ||
| 520 | |a OBJECTIVES: To evaluate the concentration-efficacy relationship, concentration-toxicity relationship and pharmacokinetic/pharmacodynamic (PK/PD) variability of L-amb in children | ||
| 520 | |a METHODS: We systematically reviewed PubMed and Embase databases following PRISMA guidelines. Eligible studies included L-amb PK/PD studies in children aged 0-18 years. Review articles, case series of <five patients, editorials and animal studies were excluded. Quality assessment was performed using the Critical Appraisal of Clinical Pharmacokinetics tool. The concentration-efficacy and concentration-toxicity relationships and PK/PD variability were analysed | ||
| 520 | |a RESULTS: In total, 4220 studies were screened; 6 were included, presenting data on 195 children. Invasive candidiasis and aspergillosis were the two most common infections treated with L-amb. Studies showed significant PK variability due to age (mean age ranged from 14 days to 17 years), body weight, non-linear PK and changes in the volume of distribution. Limited evidence supported a peak concentration/MIC (Cmax/MIC) of 25-50 for optimal efficacy and an AUC24 of >600 mg·h/L for nephrotoxicity. L-amb doses of 2.5-10 mg/kg/day were reported to achieve Cmax/MIC > 25 using an MIC of 1 mg/L | ||
| 520 | |a CONCLUSIONS: While significant PK variability was observed in children, evidence to support routine L-amb TDM was limited. Further studies on efficacy and toxicity benefits are required before routine TDM of L-amb can be recommended | ||
| 650 | 4 | |a Systematic Review | |
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Kim, Hannah Yejin |e verfasserin |4 aut | |
| 700 | 1 | |a Marais, Ben J |e verfasserin |4 aut | |
| 700 | 1 | |a McLachlan, Andrew J |e verfasserin |4 aut | |
| 700 | 1 | |a Alffenaar, Jan-Willem C |e verfasserin |4 aut | |
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