Real World Posaconazole Pharmacokinetic Data in Paediatric Stem Cell Transplant Recipients
<b>Background:</b> Invasive fungal disease is a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. Posaconazole, a broad-spectrum triazole, is widely used as prophylaxis. <b>Methods:</b> We conducted a monocent...
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MDPI AG
2025-04-01
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| author | Csaba Kassa Katalin Csordás Lídia Hau Orsolya Horváth Krisztián Kállay Gabriella Kertész Márton Kiss János Sinkó Ágnes Wolfort Gergely Kriván |
| author_facet | Csaba Kassa Katalin Csordás Lídia Hau Orsolya Horváth Krisztián Kállay Gabriella Kertész Márton Kiss János Sinkó Ágnes Wolfort Gergely Kriván |
| author_sort | Csaba Kassa |
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| description | <b>Background:</b> Invasive fungal disease is a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. Posaconazole, a broad-spectrum triazole, is widely used as prophylaxis. <b>Methods:</b> We conducted a monocentric, retrospective study to present real-world data on posaconazole trough levels in paediatric alloHSCT patients. The main objective was to determine the required daily dose of posaconazole in paediatric patients. We analysed factors influencing posaconazole levels, and the association between posaconazole levels and breakthrough fungal infection. <b>Results:</b> Among 102 allogeneic HSCT recipients, we measured posaconazole plasma concentrations in 548 blood samples. The required daily doses to reach a target range of 0.7–2.0 mg/L were 15.22 (suspension), 7.52 (tablet), and 7.84 mg/kg (intravenous). Patients aged < 13 years needed higher doses to achieve the target range. The presence of enteral symptoms during prophylaxis was associated with lower plasma concentrations (<i>p</i> < 0.001), while co-administration of proton pump inhibitors did not (<i>p</i> = 0.09). Eight breakthrough infections occurred; low levels of posaconazole (<0.7 mg/L) were observed in five out of eight cases. The Cox regression model showed that higher mean plasma concentrations decreased the hazard of breakthrough infections. <b>Conclusions:</b> The tablet and intravenous formulations of posaconazole outperformed the suspension in terms of predictability. Our analyses on breakthrough infections and posaconazole plasma levels suggest an exposure–response relationship. |
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| institution | OA Journals |
| issn | 2227-9067 |
| language | English |
| publishDate | 2025-04-01 |
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| series | Children |
| spelling | doaj-art-7af4fa8d11b94067b5fb11ce9b9edc9f2025-08-20T02:28:18ZengMDPI AGChildren2227-90672025-04-0112446710.3390/children12040467Real World Posaconazole Pharmacokinetic Data in Paediatric Stem Cell Transplant RecipientsCsaba Kassa0Katalin Csordás1Lídia Hau2Orsolya Horváth3Krisztián Kállay4Gabriella Kertész5Márton Kiss6János Sinkó7Ágnes Wolfort8Gergely Kriván9Department of Pediatric Hematology and Stem Cell Transplantation, National Institute of Hematology and Infectious Diseases, South-Pest Central Hospital, 1097 Budapest, HungaryDepartment of Pediatric Hematology and Stem Cell Transplantation, National Institute of Hematology and Infectious Diseases, South-Pest Central Hospital, 1097 Budapest, HungaryDepartment of Pediatric Hematology and Stem Cell Transplantation, National Institute of Hematology and Infectious Diseases, South-Pest Central Hospital, 1097 Budapest, HungaryPediatric Center, Semmelweis University, 1085 Budapest, HungaryDepartment of Pediatric Hematology and Stem Cell Transplantation, National Institute of Hematology and Infectious Diseases, South-Pest Central Hospital, 1097 Budapest, HungaryDepartment of Pediatric Hematology and Stem Cell Transplantation, National Institute of Hematology and Infectious Diseases, South-Pest Central Hospital, 1097 Budapest, HungaryIndependent Researcher, 1132 Budapest, HungaryHeim Pál Children’s Hospital, 1089 Budapest, HungaryDepartment of Hematology and Stem Cell Transplantation, National Institute of Hematology and Infectious Diseases, South-Pest Central Hospital, 1097 Budapest, HungaryDepartment of Pediatric Hematology and Stem Cell Transplantation, National Institute of Hematology and Infectious Diseases, South-Pest Central Hospital, 1097 Budapest, Hungary<b>Background:</b> Invasive fungal disease is a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. Posaconazole, a broad-spectrum triazole, is widely used as prophylaxis. <b>Methods:</b> We conducted a monocentric, retrospective study to present real-world data on posaconazole trough levels in paediatric alloHSCT patients. The main objective was to determine the required daily dose of posaconazole in paediatric patients. We analysed factors influencing posaconazole levels, and the association between posaconazole levels and breakthrough fungal infection. <b>Results:</b> Among 102 allogeneic HSCT recipients, we measured posaconazole plasma concentrations in 548 blood samples. The required daily doses to reach a target range of 0.7–2.0 mg/L were 15.22 (suspension), 7.52 (tablet), and 7.84 mg/kg (intravenous). Patients aged < 13 years needed higher doses to achieve the target range. The presence of enteral symptoms during prophylaxis was associated with lower plasma concentrations (<i>p</i> < 0.001), while co-administration of proton pump inhibitors did not (<i>p</i> = 0.09). Eight breakthrough infections occurred; low levels of posaconazole (<0.7 mg/L) were observed in five out of eight cases. The Cox regression model showed that higher mean plasma concentrations decreased the hazard of breakthrough infections. <b>Conclusions:</b> The tablet and intravenous formulations of posaconazole outperformed the suspension in terms of predictability. Our analyses on breakthrough infections and posaconazole plasma levels suggest an exposure–response relationship.https://www.mdpi.com/2227-9067/12/4/467posaconazoletherapeutic drug monitoringstem cell transplantationpaediatricbreakthrough infection |
| spellingShingle | Csaba Kassa Katalin Csordás Lídia Hau Orsolya Horváth Krisztián Kállay Gabriella Kertész Márton Kiss János Sinkó Ágnes Wolfort Gergely Kriván Real World Posaconazole Pharmacokinetic Data in Paediatric Stem Cell Transplant Recipients Children posaconazole therapeutic drug monitoring stem cell transplantation paediatric breakthrough infection |
| title | Real World Posaconazole Pharmacokinetic Data in Paediatric Stem Cell Transplant Recipients |
| title_full | Real World Posaconazole Pharmacokinetic Data in Paediatric Stem Cell Transplant Recipients |
| title_fullStr | Real World Posaconazole Pharmacokinetic Data in Paediatric Stem Cell Transplant Recipients |
| title_full_unstemmed | Real World Posaconazole Pharmacokinetic Data in Paediatric Stem Cell Transplant Recipients |
| title_short | Real World Posaconazole Pharmacokinetic Data in Paediatric Stem Cell Transplant Recipients |
| title_sort | real world posaconazole pharmacokinetic data in paediatric stem cell transplant recipients |
| topic | posaconazole therapeutic drug monitoring stem cell transplantation paediatric breakthrough infection |
| url | https://www.mdpi.com/2227-9067/12/4/467 |
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