Efficacy and Safety Assessment of Antifungal Prophylaxis with Posaconazole Using Therapeutic Drug Monitoring in Pediatric Patients with Oncohematological Disorders—A Single-Centre Study

Introduction: Posaconazole is recommended for prophylaxis in pediatric immunocompromised patients. Due to its variability in bioavailability and drug-to-drug interactions, EBMT recommends regimens based on therapeutic drug monitoring (TDM). Materials and methods: In total, 171 oncohematological pedi...

Full description

Saved in:
Bibliographic Details
Main Authors: Karolina Liszka, Paweł Marschollek, Dawid Przystupski, Jowita Frączkiewicz, Monika Mielcarek-Siedziuk, Igor Olejnik, Zuzanna Gamrot, Natalia Haze, Agnieszka Kwella, Paulina Zalewska, Matylda Resztak, Marek Ussowicz, Krzysztof Kałwak
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/11/1/38
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832588177088446464
author Karolina Liszka
Paweł Marschollek
Dawid Przystupski
Jowita Frączkiewicz
Monika Mielcarek-Siedziuk
Igor Olejnik
Zuzanna Gamrot
Natalia Haze
Agnieszka Kwella
Paulina Zalewska
Matylda Resztak
Marek Ussowicz
Krzysztof Kałwak
author_facet Karolina Liszka
Paweł Marschollek
Dawid Przystupski
Jowita Frączkiewicz
Monika Mielcarek-Siedziuk
Igor Olejnik
Zuzanna Gamrot
Natalia Haze
Agnieszka Kwella
Paulina Zalewska
Matylda Resztak
Marek Ussowicz
Krzysztof Kałwak
author_sort Karolina Liszka
collection DOAJ
description Introduction: Posaconazole is recommended for prophylaxis in pediatric immunocompromised patients. Due to its variability in bioavailability and drug-to-drug interactions, EBMT recommends regimens based on therapeutic drug monitoring (TDM). Materials and methods: In total, 171 oncohematological pediatric patients on posaconazole prophylaxis were included. Full pharmacokinetic posaconazole profiles were assessed in 51 children. The efficacy and safety of posaconazole was evaluated by measuring the drug concentration, with dose modification attempted in patients with suboptimal results. The influence of modifying factors on the posaconazole plasma concentration (PPC) was investigated. Results: An insufficient PPC was the main issue, but no significant increase in prophylaxis failure was reported. The modification of the dosage resulted in the optimization of PPC in 50% of patients. No significant correlation between age, gender, diagnosis or the posaconazole dosage and the PPC was found. HCT, total parenteral nutrition and diarrhea were associated with a lower PPC. Hypoalbuminemia was related to both higher and lower PPC. The concomitant administration of specified drugs significantly impacted the PPC. Conclusions: TDM allows the identification of patients receiving non-optimal treatment and offers an opportunity to improve the efficacy and safety of the therapy. However, further research involving larger patient groups and longer observation periods are needed to determine the optimal dosing and target PPC in pediatric patients.
format Article
id doaj-art-0b66d435d3c7450bb2a4161658518cc9
institution Kabale University
issn 2309-608X
language English
publishDate 2025-01-01
publisher MDPI AG
record_format Article
series Journal of Fungi
spelling doaj-art-0b66d435d3c7450bb2a4161658518cc92025-01-24T13:37:19ZengMDPI AGJournal of Fungi2309-608X2025-01-011113810.3390/jof11010038Efficacy and Safety Assessment of Antifungal Prophylaxis with Posaconazole Using Therapeutic Drug Monitoring in Pediatric Patients with Oncohematological Disorders—A Single-Centre StudyKarolina Liszka0Paweł Marschollek1Dawid Przystupski2Jowita Frączkiewicz3Monika Mielcarek-Siedziuk4Igor Olejnik5Zuzanna Gamrot6Natalia Haze7Agnieszka Kwella8Paulina Zalewska9Matylda Resztak10Marek Ussowicz11Krzysztof Kałwak12Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandDepartment of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandDepartment of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandDepartment of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandDepartment of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandDepartment of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandDepartment of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandDepartment of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandDepartment of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandMonitLab Laboratory, 61-612 Poznan, PolandDepartment of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, PolandDepartment of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandDepartment of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandIntroduction: Posaconazole is recommended for prophylaxis in pediatric immunocompromised patients. Due to its variability in bioavailability and drug-to-drug interactions, EBMT recommends regimens based on therapeutic drug monitoring (TDM). Materials and methods: In total, 171 oncohematological pediatric patients on posaconazole prophylaxis were included. Full pharmacokinetic posaconazole profiles were assessed in 51 children. The efficacy and safety of posaconazole was evaluated by measuring the drug concentration, with dose modification attempted in patients with suboptimal results. The influence of modifying factors on the posaconazole plasma concentration (PPC) was investigated. Results: An insufficient PPC was the main issue, but no significant increase in prophylaxis failure was reported. The modification of the dosage resulted in the optimization of PPC in 50% of patients. No significant correlation between age, gender, diagnosis or the posaconazole dosage and the PPC was found. HCT, total parenteral nutrition and diarrhea were associated with a lower PPC. Hypoalbuminemia was related to both higher and lower PPC. The concomitant administration of specified drugs significantly impacted the PPC. Conclusions: TDM allows the identification of patients receiving non-optimal treatment and offers an opportunity to improve the efficacy and safety of the therapy. However, further research involving larger patient groups and longer observation periods are needed to determine the optimal dosing and target PPC in pediatric patients.https://www.mdpi.com/2309-608X/11/1/38posaconazoletherapeutic drug monitoring (TDM)antifungal prophylaxis
spellingShingle Karolina Liszka
Paweł Marschollek
Dawid Przystupski
Jowita Frączkiewicz
Monika Mielcarek-Siedziuk
Igor Olejnik
Zuzanna Gamrot
Natalia Haze
Agnieszka Kwella
Paulina Zalewska
Matylda Resztak
Marek Ussowicz
Krzysztof Kałwak
Efficacy and Safety Assessment of Antifungal Prophylaxis with Posaconazole Using Therapeutic Drug Monitoring in Pediatric Patients with Oncohematological Disorders—A Single-Centre Study
Journal of Fungi
posaconazole
therapeutic drug monitoring (TDM)
antifungal prophylaxis
title Efficacy and Safety Assessment of Antifungal Prophylaxis with Posaconazole Using Therapeutic Drug Monitoring in Pediatric Patients with Oncohematological Disorders—A Single-Centre Study
title_full Efficacy and Safety Assessment of Antifungal Prophylaxis with Posaconazole Using Therapeutic Drug Monitoring in Pediatric Patients with Oncohematological Disorders—A Single-Centre Study
title_fullStr Efficacy and Safety Assessment of Antifungal Prophylaxis with Posaconazole Using Therapeutic Drug Monitoring in Pediatric Patients with Oncohematological Disorders—A Single-Centre Study
title_full_unstemmed Efficacy and Safety Assessment of Antifungal Prophylaxis with Posaconazole Using Therapeutic Drug Monitoring in Pediatric Patients with Oncohematological Disorders—A Single-Centre Study
title_short Efficacy and Safety Assessment of Antifungal Prophylaxis with Posaconazole Using Therapeutic Drug Monitoring in Pediatric Patients with Oncohematological Disorders—A Single-Centre Study
title_sort efficacy and safety assessment of antifungal prophylaxis with posaconazole using therapeutic drug monitoring in pediatric patients with oncohematological disorders a single centre study
topic posaconazole
therapeutic drug monitoring (TDM)
antifungal prophylaxis
url https://www.mdpi.com/2309-608X/11/1/38
work_keys_str_mv AT karolinaliszka efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy
AT pawełmarschollek efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy
AT dawidprzystupski efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy
AT jowitafraczkiewicz efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy
AT monikamielcareksiedziuk efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy
AT igorolejnik efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy
AT zuzannagamrot efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy
AT nataliahaze efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy
AT agnieszkakwella efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy
AT paulinazalewska efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy
AT matyldaresztak efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy
AT marekussowicz efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy
AT krzysztofkałwak efficacyandsafetyassessmentofantifungalprophylaxiswithposaconazoleusingtherapeuticdrugmonitoringinpediatricpatientswithoncohematologicaldisordersasinglecentrestudy