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比较在有和没有潜在差异的患者中,伊曲康唑与其他抗真菌疗法在侵袭性真菌感染的真实世界使用情况:一项多中心回顾性研究。

Comparing the Real-World Use of Isavuconazole to Other Anti-Fungal Therapy for Invasive Fungal Infections in Patients with and without Underlying Disparities: A Multi-Center Retrospective Study.

作者信息

Batista Marjorie Vieira, Ussetti Maria Piedad, Jiang Ying, Neofytos Dionysios, Cortez Anita Cassoli, Feriani Diego, Schmidt-Filho Jayr, França-Silva Ivan Leonardo Avelino, Raad Issam, Hachem Ray

机构信息

Department of Infectious Diseases, AC Camargo Cancer Center, São Paulo 01509-010, SP, Brazil.

Transplant Department, Puerta de Hierro University Hospital, 28222 Majadahonda, Spain.

出版信息

J Fungi (Basel). 2023 Jan 27;9(2):166. doi: 10.3390/jof9020166.

Abstract

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among immunocompromised patients with underlying malignancies and prior transplants. FDA approved Isavuconazole as a primary therapy for Invasive Aspergillosis (IA) and Mucormycosis. This study aims to compare the real-world clinical outcomes and safety of isavuconazole to voriconazole and an amphotericin B-based regimen in patients with underlying malignancies and a transplant. In addition, the response to anti-fungal therapy and the outcome were compared among patients with a disparity (elderly, obese patients, patients with renal insufficiency and diabetes mellitus) versus those with no disparity. We performed a multicenter retrospective study, including patients with cancer diagnosed with an invasive fungal infection, and treated primarily with isavuconazole, voriconazole or amphotericin B. Clinical, radiologic findings, response to therapy and therapy related adverse events were evaluated during 12 weeks of follow-up. We included 112 patients aged 14 to 77 years, and most of the IFIs were classified into definite (29) or probable (51). Most cases were invasive aspergillosis (79%), followed by fusariosis (8%). Amphotericin B were used more frequently as primary therapy (38%) than isavuconazole (30%) or voriconazole (31%). Twenty one percent of the patients presented adverse events related to primary therapy, with patients receiving isavuconazole presenting less adverse events when compared to voriconazole and amphotericin ( < 0.001; = 0.019). Favorable response to primary therapy during 12 weeks of follow-up were similar when comparing amphotericin B, isavuconazole or voriconazole use. By univariate analysis, the overall cause of mortality at 12 weeks was higher in patients receiving amphotericin B as primary therapy. However, by multivariate analysis, Fusarium infection, invasive pulmonary infection or sinus infection were the only independent risk factors associated with mortality. In the treatment of IFI for patients with underlying malignancy or a transplant, Isavuconazole was associated with the best safety profile compared to voriconazole or amphotericin B-based regimen. Regardless of the type of anti-fungal therapy used, invasive Fusarium infections and invasive pulmonary or sinus infections were the only risk factors associated with poor outcomes. Disparity criteria did not affect the response to anti-fungal therapy and overall outcome, including mortality.

摘要

侵袭性真菌感染(IFI)是患有潜在恶性肿瘤和既往接受过移植的免疫功能低下患者发病和死亡的主要原因。美国食品药品监督管理局(FDA)批准了艾沙康唑作为侵袭性曲霉病(IA)和毛霉病的一线治疗药物。本研究旨在比较艾沙康唑与伏立康唑以及基于两性霉素B的治疗方案在患有潜在恶性肿瘤和接受过移植的患者中的真实世界临床疗效和安全性。此外,还比较了存在差异的患者(老年人、肥胖患者、肾功能不全患者和糖尿病患者)与无差异患者对抗真菌治疗的反应及治疗结果。我们进行了一项多中心回顾性研究,纳入了被诊断为侵袭性真菌感染且主要接受艾沙康唑、伏立康唑或两性霉素B治疗的癌症患者。在12周的随访期间评估临床、影像学检查结果、对治疗的反应以及与治疗相关的不良事件。我们纳入了112名年龄在14至77岁之间的患者,大多数IFI被分类为确诊(29例)或很可能(51例)。大多数病例为侵袭性曲霉病(79%),其次是镰刀菌病(8%)。两性霉素B作为一线治疗药物(38%)的使用频率高于艾沙康唑(30%)或伏立康唑(31%)。21%的患者出现了与一线治疗相关的不良事件,与伏立康唑和两性霉素相比,接受艾沙康唑治疗的患者出现的不良事件较少(<0.001;=0.019)。在比较使用两性霉素B、艾沙康唑或伏立康唑时,随访12周期间对一线治疗的良好反应相似。通过单因素分析,接受两性霉素B作为一线治疗的患者在第12周时的总体死亡率较高。然而,通过多因素分析,镰刀菌感染、侵袭性肺部感染或鼻窦感染是与死亡率相关的唯一独立危险因素。在治疗患有潜在恶性肿瘤或接受过移植的IFI患者时,与伏立康唑或基于两性霉素B的治疗方案相比,艾沙康唑具有最佳的安全性。无论使用何种抗真菌治疗类型,侵袭性镰刀菌感染以及侵袭性肺部或鼻窦感染是与不良结局相关的唯一危险因素。差异标准不影响对抗真菌治疗的反应和总体结局,包括死亡率。

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