Chiusaroli Lorenzo, Barbieri Elisa, Dell'Anna Lucia, Petris Maria Grazia, Liberati Cecilia, Reggiani Giulia, De Pieri Marica, Mengato Daniele, Marzollo Antonio, Gabelli Maria, Giaquinto Carlo, Biffi Alessandra, Donà Daniele
Department for Women's and Children's Health-Division of Pediatric Infectious Diseases, Padua University Hospital, Padua, Italy.
Department for Women's and Children's Health-Pediatric Hematology, Oncology and Stem Cell Transplant, Padua University Hospital, Padua, Italy.
J Antimicrob Chemother. 2025 Mar 3;80(3):802-809. doi: 10.1093/jac/dkae479.
The prevention of invasive fungal infections (IFIs) is crucial for paediatric haemato-oncological patients. This study evaluates the clinical efficacy and side-effects of posaconazole and liposomal amphotericin B (L-AmB) as primary prophylaxis.
This cohort study included patients aged 3 months to 21 years who received posaconazole or L-AmB (5 mg/kg twice weekly) as prophylaxis from January 2017 to March 2022 at the Hemato-oncological Pediatric Unit, University Hospital of Padua, Italy. Outcomes included adverse events and IFI diagnoses after the start of prophylaxis. Separate analyses were performed for patients with ALL and non-ALL diagnoses, and high-risk and low-risk groups. Cumulative incidence was calculated using the Kaplan-Meier estimator, with significant differences assessed using the log-rank test. Hazard ratios (HR) were estimated using Cox regression.
Fifty-one patients received posaconazole, and 37 received L-AmB. Adverse events occurred in 26% of L-AmB patients and 5.6% of posaconazole patients. IFI breakthrough events were similar in both groups (four events each). In ALL patients, 41% experienced adverse events with L-AmB, compared to 5% with posaconazole. After 1 year, the probability of adverse events was lower in the posaconazole group (54% versus 65%, P < 0.001). Overall, posaconazole was associated with a 91% lower risk of adverse events (HR: 0.07, P < 0.001). Among high-risk patients, IFI breakthrough rates were similar between groups (P = 0.964).
Posaconazole was associated with fewer adverse events than L-AmB, and both drugs showed similar efficacy in preventing IFI breakthroughs, making posaconazole a viable alternative for primary prophylaxis.
侵袭性真菌感染（IFI）的预防对儿科血液肿瘤患者至关重要。本研究评估泊沙康唑和脂质体两性霉素B（L-AmB）作为一级预防的临床疗效和副作用。
本队列研究纳入了2017年1月至2022年3月在意大利帕多瓦大学医院血液肿瘤儿科接受泊沙康唑或L-AmB（5mg/kg，每周两次）预防治疗的3个月至21岁患者。观察指标包括开始预防治疗后的不良事件和IFI诊断。对急性淋巴细胞白血病（ALL）和非ALL诊断患者以及高危和低危组进行了单独分析。使用Kaplan-Meier估计器计算累积发病率，使用对数秩检验评估显著差异。使用Cox回归估计风险比（HR）。
51例患者接受了泊沙康唑治疗，37例接受了L-AmB治疗。L-AmB组26%的患者出现不良事件，泊沙康唑组为5.6%。两组的IFI突破性事件相似（每组各4例）。在ALL患者中，41%的患者使用L-AmB时出现不良事件，而使用泊沙康唑的患者为5%。1年后，泊沙康唑组不良事件的发生率较低（54%对65%，P<0.001）。总体而言，泊沙康唑的不良事件风险降低了91%（HR：0.07，P<0.001）。在高危患者中，两组的IFI突破性发生率相似（P=0.964）。
与L-AmB相比，泊沙康唑的不良事件更少，且两种药物在预防IFI突破性感染方面显示出相似的疗效，这使得泊沙康唑成为一级预防的可行替代药物。
