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脂质体两性霉素B和艾沙康唑成功治疗一名成年HIV感染者的播散性隐球菌病:病例报告及文献综述

Successful treatment of disseminated cryptococcosis with liposomal amphotericin B and isavuconazole in an adult living with HIV: A case report and literature review.

作者信息

Kawaguchi Takeshi, Kitamura Akiko, Kimura Masatoshi, Rikitake Yuki, Iwao Chihiro, Iwao Kosho, Sumiyoshi Makoto, Kariya Yumi, Matsuda Motohiro, Umekita Kunihiko, Takajo Ichiro, Moriguchi-Goto Sayaka, Yamashita Atsushi, Matsumoto Kana, Miyazaki Taiga

机构信息

Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

出版信息

J Infect Chemother. 2025 Jan;31(1):102534. doi: 10.1016/j.jiac.2024.10.002. Epub 2024 Oct 6.

Abstract

Treating disseminated cryptococcosis in people with human immunodeficiency virus (HIV) is challenging due to the limited availability of effective antifungals. Although isavuconazole has antifungal activity against Cryptococcus neoformans, clinical evidence is sparse because this new drug has not been approved for the treatment of cryptococcosis in the US or Europe. Here, we report a case of HIV-associated cryptococcal meningitis that relapsed during maintenance therapy with fluconazole. A Japanese man in his 20s was diagnosed with HIV-1 infection and cryptococcal meningitis. The patient was intolerant to flucytosine and was treated with liposomal amphotericin B monotherapy for 2 weeks as induction therapy, followed by fluconazole (400 mg/day) for 3 months as consolidation therapy. Four months after starting maintenance therapy with fluconazole (200 mg/day), the patient presented with fever and cough, leading to readmission to our hospital. Biopsies of a nodule in the left lung and a left cervical lymph node led to the diagnosis of disseminated cryptococcosis (pulmonary cryptococcosis and cryptococcal lymphadenitis). Although a combination of fluconazole and liposomal amphotericin B was ineffective, the patient was successfully treated with an induction therapy combining isavuconazole and liposomal amphotericin B, followed by a maintenance therapy with isavuconazole. The patient received isavuconazole orally except for loading doses, achieving stable blood concentration levels. Moreover, we observed that blood levels of amphotericin B increased gradually with repeated administration. Therefore, isavuconazole may have a potential role in the treatment of cryptococcosis, and clinical trials involving larger numbers of cases are needed to confirm its efficacy and safety.

摘要

由于有效抗真菌药物的可获得性有限,治疗人类免疫缺陷病毒(HIV)感染者的播散性隐球菌病具有挑战性。尽管艾沙康唑对新型隐球菌具有抗真菌活性,但临床证据稀少,因为这种新药在美国或欧洲尚未被批准用于治疗隐球菌病。在此,我们报告一例在氟康唑维持治疗期间复发的HIV相关隐球菌性脑膜炎病例。一名20多岁的日本男性被诊断为HIV-1感染和隐球菌性脑膜炎。该患者对氟胞嘧啶不耐受,接受脂质体两性霉素B单药治疗2周作为诱导治疗,随后接受氟康唑(400毫克/天)治疗3个月作为巩固治疗。在开始使用氟康唑(200毫克/天)维持治疗4个月后,患者出现发热和咳嗽,导致再次入院。对左肺结节和左颈淋巴结进行活检后诊断为播散性隐球菌病(肺隐球菌病和隐球菌性淋巴结炎)。尽管氟康唑和脂质体两性霉素B联合治疗无效,但该患者通过艾沙康唑和脂质体两性霉素B联合诱导治疗,随后用艾沙康唑维持治疗获得成功。除负荷剂量外,患者口服艾沙康唑,实现了稳定的血药浓度水平。此外,我们观察到两性霉素B的血药水平随着重复给药而逐渐升高。因此,艾沙康唑可能在隐球菌病治疗中具有潜在作用,需要开展涉及更多病例的临床试验来证实其疗效和安全性。

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