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伊曲康唑预防肺移植受者真菌感染的疗效与伏立康唑相当,且耐受性更好。

Isavuconazole Is as Effective as and Better Tolerated Than Voriconazole for Antifungal Prophylaxis in Lung Transplant Recipients.

机构信息

Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

出版信息

Clin Infect Dis. 2021 Aug 2;73(3):416-426. doi: 10.1093/cid/ciaa652.

Abstract

BACKGROUND

Invasive fungal infections (IFIs) are common following lung transplantation. Isavuconazole is unstudied as prophylaxis in organ transplant recipients. We compared effectiveness and tolerability of isavuconazole and voriconazole prophylaxis in lung transplant recipients.

METHODS

A single-center, retrospective study of patients who received isavuconazole (September 2015-February 2018) or voriconazole (September 2013-September 2015) for antifungal prophylaxis. IFIs were defined by EORTC/MSG criteria.

RESULTS

Patients received isavuconazole (n = 144) or voriconazole (n = 156) for median 3.4 and 3.1 months, respectively. Adjunctive inhaled amphotericin B (iAmB) was administered to 100% and 41% of patients in the respective groups. At 1 year, 8% of patients receiving isavuconazole or voriconazole developed IFIs. For both groups, 70% and 30% of IFIs were caused by molds and yeasts, respectively, and breakthrough IFI (bIFI) rate was 3%. Outcomes did not significantly differ for patients receiving or not receiving iAmB. Independent risk factors for bIFI and breakthrough invasive mold infection (bIMI) were mold-positive respiratory culture and red blood cell transfusion >7 units at transplant. Bronchial necrosis >2 cm from anastomosis and basiliximab induction were also independent risk factors for bIMI. Isavuconazole and voriconazole were discontinued prematurely due to adverse events in 11% and 36% of patients, respectively (P = .0001). Most common causes of voriconazole and isavuconazole discontinuation were hepatotoxicity and lack of oral intake, respectively. Patients receiving ≥90 days prophylaxis had fewer IFIs at 1 year (3% vs 9%, P = .02). IFIs were associated with increased mortality (P = .0001) and longer hospitalizations (P = .0005).

CONCLUSIONS

Isavuconazole was effective and well tolerated as antifungal prophylaxis following lung transplantation.

摘要

背景

肺部移植后常发生侵袭性真菌感染(IFI)。伊曲康唑尚未在器官移植受者中进行预防研究。我们比较了伊曲康唑和伏立康唑预防肺部移植受者IFI 的有效性和耐受性。

方法

这是一项单中心、回顾性研究,纳入了 2015 年 9 月至 2018 年 2 月期间接受伊曲康唑(n=144)或伏立康唑(n=156)预防 IFI 的患者。IFI 的定义符合 EORTC/MSG 标准。

结果

患者分别接受伊曲康唑(中位时间 3.4 个月)和伏立康唑(中位时间 3.1 个月)预防治疗。两组患者均有 100%和 41%的患者接受了辅助吸入两性霉素 B(iAmB)治疗。在 1 年时,伊曲康唑或伏立康唑组分别有 8%和 30%的患者发生 IFI。两组患者的 IFI 中,分别有 70%和 30%由霉菌和酵母菌引起,突破性 IFI(bIFI)发生率为 3%。是否接受 iAmB 治疗与两组患者的预后均无显著相关性。bIFI 和突破性侵袭性霉菌感染(bIMI)的独立危险因素为霉菌阳性呼吸道培养和移植时红细胞输注量>7 单位。支气管坏死距吻合口>2cm 和巴利昔单抗诱导也是 bIMI 的独立危险因素。由于不良反应,伊曲康唑和伏立康唑分别有 11%和 36%的患者提前停药(P=0.0001)。伏立康唑和伊曲康唑停药的最常见原因分别是肝毒性和无法口服摄入。接受预防治疗≥90 天的患者在 1 年时 IFI 发生率较低(3%比 9%,P=0.02)。IFI 与死亡率增加(P=0.0001)和住院时间延长(P=0.0005)相关。

结论

伊曲康唑是一种有效的抗真菌预防药物,可用于肺部移植。

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