Weerdenburg Heather, Walker Hannah, Haeusler Gabrielle M, Cole Theresa, Curtis Nigel, Duffull Stephen, Gwee Amanda
Department of Pharmacy, Children's Cancer Centre, General Medicine and Allergy and Immunology, Royal Children's Hospital, Parkville, Australia.
Antimicrobials, Clinical Paediatrics, and Infectious Diseases Groups, Murdoch Children's Research Institute, Parkville, Australia.
J Antimicrob Chemother. 2025 Apr 2;80(4):897-907. doi: 10.1093/jac/dkae473.
Posaconazole is used to prevent and treat invasive fungal infections (IFIs) in immunocompromised children, including those undergoing cancer treatment or HSCT. Despite differences in pharmacokinetics and IFI epidemiology between children and adults, therapeutic targets established in adult studies are often applied to children.
This systematic review evaluated the correlation between serum posaconazole concentrations and clinical outcomes of IFI prophylaxis and treatment in children with malignancies or HSCT recipients.
Four databases (Cochrane, Embase, MEDLINE and PubMed) were searched for studies involving children (≤18 years old) receiving cancer treatment or HSCT that reported posaconazole serum concentrations and treatment outcomes. Animal studies, those primarily in adult (>18 years old) populations, non-malignant conditions (excluding HSCT), case reports, letters, editorials, conference abstracts and narrative reviews were excluded. Bias was assessed using the Newcastle-Ottawa scale.
Nineteen studies were included: 12 reported outcomes of posaconazole prophylaxis; two of treatment; and five of both. For prophylaxis, breakthrough IFIs occurred in 1%-12% of children. All but one occurred with serum concentrations of ≤0.7 mg/L. For treatment, no clear association was observed between a trough concentration of >1.0 mg/L and treatment efficacy, with poor outcomes reported for serum concentrations ranging between 0.2 and 4.8 mg/L. Overall, quality of evidence was poor (medium to high risk of bias for 18 papers, low risk for 1 paper) and there was variation in IFI definitions across studies.
This review supports current recommendations for posaconazole prophylaxis in paediatric oncology and HSCT recipients. The absence of a clear correlation found between serum trough concentrations and treatment efficacy highlights the need for further studies to determine optimal therapeutic targets for treatment.
泊沙康唑用于预防和治疗免疫功能低下儿童的侵袭性真菌感染（IFI），包括正在接受癌症治疗或造血干细胞移植（HSCT）的儿童。尽管儿童和成人在药代动力学和IFI流行病学方面存在差异，但成人研究中确立的治疗靶点常常应用于儿童。
本系统评价评估了泊沙康唑血清浓度与恶性肿瘤儿童或HSCT受者IFI预防和治疗临床结局之间的相关性。
检索了四个数据库（Cochrane、Embase、MEDLINE和PubMed），查找涉及接受癌症治疗或HSCT的儿童（≤18岁）且报告了泊沙康唑血清浓度和治疗结局的研究。排除动物研究、主要针对成人（>18岁）人群的研究、非恶性疾病（不包括HSCT）、病例报告、信函、社论、会议摘要和叙述性综述。使用纽卡斯尔-渥太华量表评估偏倚。
纳入19项研究：12项报告了泊沙康唑预防的结局；2项报告了治疗的结局；5项报告了两者的结局。对于预防，1%-12%的儿童发生突破性IFI。除1例之外，所有突破性IFI均发生在血清浓度≤0.7mg/L时。对于治疗，未观察到谷浓度>1.0mg/L与治疗疗效之间存在明确关联，血清浓度在0.2至4.8mg/L之间时报告的结局较差。总体而言，证据质量较差（18篇论文存在中度至高偏倚风险，1篇论文存在低偏倚风险），且各研究中IFI的定义存在差异。
本综述支持目前关于泊沙康唑在儿科肿瘤学和HSCT受者中预防的建议。血清谷浓度与治疗疗效之间未发现明确相关性，这凸显了进一步研究以确定治疗的最佳治疗靶点的必要性。
