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急性白血病患者播散性两性霉素 B 耐药性镰刀菌病:两例报告。

Disseminated amphotericin-resistant fusariosis in acute leukemia patients: report of two cases.

机构信息

Department of Infection Diseases, Brigadeiro Hospital, Av. Jandira, 79/231, São Paulo, SP, 04080-000, Brazil.

出版信息

Mycopathologia. 2013 Feb;175(1-2):107-14. doi: 10.1007/s11046-012-9585-0. Epub 2012 Oct 18.

Abstract

Disseminated fusariosis has emerged as a significant, usually fatal infection in immunocompromised hosts despite antifungal treatment. We describe here two patients with acute leukemia who developed disseminated amphotericin-resistant fusariosis, and review of six studies of cases series in the literature. Two Fusarium solani strains were isolated from blood and skin cultures of one patient, and one strain from the blood culture of the second patient. Both patients died despite antifungal treatment. Strains were identified by sequencing of ITS1 and ITS4 regions. Random amplified polymorphic DNA analysis of the three F. solani isolates showed a low degree of similarity. Screening for Fusarium spp. contaminants within our facility was negative. Using the CLSI M-38-A2 broth dilution method and E tests(®), we found that the MICs were low for voriconazole (0.12 and 0.5 mg/L, respectively), unexpectedly high for amphotericin B (≥8 and ≥32 μg/mL, respectively) and itraconazole (≥16 mg/ml). Patients with leukemia or persistent neutropenia should be assessed for disseminated fungal infections, including biopsy and skin cultures. Antifungal susceptibility tests are important due to the possibility of the strains being amphotericin resistant. Treatments must be aggressive, with high doses of antifungals or combined therapy.

摘要

播散性镰孢菌病已成为免疫功能低下宿主中一种重要的、通常致命的感染,尽管进行了抗真菌治疗。我们在此描述了两名发生播散性两性霉素 B 耐药镰孢菌病的急性白血病患者,并对文献中 6 项病例系列研究进行了回顾。一名患者的血液和皮肤培养物中分离出 2 株茄病镰刀菌,另一名患者的血液培养物中分离出 1 株。尽管进行了抗真菌治疗,但两名患者均死亡。通过 ITS1 和 ITS4 区域的测序鉴定了菌株。对 3 株 F. solani 分离株的随机扩增多态性 DNA 分析显示出低度相似性。对我们机构内的 Fusarium spp. 污染物进行筛查为阴性。使用 CLSI M-38-A2 肉汤稀释法和 E 试验(®),我们发现伏立康唑的 MIC 较低(分别为 0.12 和 0.5mg/L),两性霉素 B(分别为≥8 和≥32μg/mL)和伊曲康唑(≥16mg/ml)的 MIC 出乎意料地高。患有白血病或持续性中性粒细胞减少症的患者应评估是否发生播散性真菌感染,包括活检和皮肤培养。由于菌株可能具有两性霉素耐药性,因此抗真菌药敏试验很重要。治疗必须积极,使用高剂量的抗真菌药物或联合治疗。

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