Département de Néphrologie et Transplantation d'organes, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Laboratoire de Mycologie-Parasitologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
Transpl Infect Dis. 2021 Dec;23(6):e13745. doi: 10.1111/tid.13745. Epub 2021 Oct 26.
Preventive strategies for invasive aspergillosis (IA) have still not been determined in heart transplant recipients whereas IA leads to a high mortality rate at 12 months posttransplantation. The use of voriconazole or echinocandins was proposed but can favor emergence of Aspergillus or Candida sp. resistant strains or promote neurological and liver disorders in some patients.
To assess whether universal prophylaxis with weekly high-dose of liposomal amphotericin-B (L-AmB) can safely prevent IA in heart transplant recipients.
PATIENTS/METHODS: Retrospective before/after study that included 142 patients who received heart transplantation between 2010 and 2019 at the University Hospital of Toulouse (France). Weekly high dose of L-AmB (7.5 mg/kg/week) was used as universal prophylaxis from 2016 because of high environmental exposure to Aspergillus sp. and high incidence of IA.
Cumulative 1-year incidence of IA decreased from 23% to 5% after introduction of L-Amb prophylaxis. Multivariate analysis (Cox model) identified L-AmB prophylaxis as a protective factor against IA (hazard ratio [HR] 0.21 [95% confidence interval 0; 0.92], p = .04), whereas postoperative renal replacement therapy was associated with IA (HR 3.6 [95% confidence interval 1.38; 9.3], p = .001), after correction for confounding effects (induction regimen, methylprednisolone pulses and history of hematological malignancy). The incidence of acute kidney injury requiring renal replacement therapy was similar in the two groups, suggesting a low risk of kidney toxicity when L-AmB is used weekly. No patient developed severe kidney electrolyte loss nor L-AmB-related anaphylaxis.
Once-weekly high-dose L-AmB is safe and may prevent the development of IA after heart transplantation.
预防侵袭性曲霉菌病(IA)的策略在心脏移植受者中仍未确定,而 IA 会导致移植后 12 个月的高死亡率。曾提出使用伏立康唑或棘白菌素,但这可能会导致曲霉菌或念珠菌耐药菌株的出现,或在某些患者中引发神经和肝脏疾病。
评估每周高剂量脂质体两性霉素 B(L-AmB)的预防性应用是否可以安全预防心脏移植受者的 IA。
患者/方法:回顾性的前后研究,纳入了 2010 年至 2019 年在法国图卢兹大学医院接受心脏移植的 142 名患者。由于曲霉菌暴露环境高和 IA 发生率高,自 2016 年开始每周使用 7.5mg/kg/周的高剂量 L-AmB 作为预防性应用。
在引入 L-Amb 预防后,IA 的 1 年累积发生率从 23%降至 5%。多变量分析(Cox 模型)确定 L-AmB 预防是 IA 的保护因素(风险比 [HR] 0.21 [95%置信区间 0;0.92],p =.04),而术后肾脏替代治疗与 IA 相关(HR 3.6 [95%置信区间 1.38;9.3],p =.001),在纠正混杂效应(诱导方案、甲基强的松龙冲击和血液恶性肿瘤史)后。两组急性肾损伤需要肾脏替代治疗的发生率相似,表明每周使用 L-AmB 的肾脏毒性风险较低。没有患者出现严重的肾脏电解质丢失或与 L-AmB 相关的过敏反应。
每周一次的高剂量 L-AmB 是安全的,可能预防心脏移植后 IA 的发生。