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癌症患者中的葡萄牙念珠菌血症:两性霉素B治疗失败的危险因素及预后

Candida lusitaniae fungemia in cancer patients: risk factors for amphotericin B failure and outcome.

作者信息

Atkinson Bradley J, Lewis Russell E, Kontoyiannis Dimitrios P

机构信息

Department of Pharmacy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Med Mycol. 2008 Sep;46(6):541-6. doi: 10.1080/13693780801968571.

DOI:10.1080/13693780801968571
PMID:19180749
Abstract

Candida lusitaniae, a Candida species frequently resistant to amphotericin B (AMB), is a rare cause of candidemia. The clinical significance of this in vitro resistant phenotype, the risk factors for, and the clinical presentation of C. lusitaniae fungemia in comparison with those of Candida albicans have not been completely characterized. We reviewed 13 consecutive cases of C. lusitaniae fungemia in cancer patients and compared them with 41 consecutive cases of C. albicans fungemia (1990-2004). The AMB mutational frequency and rate of fungicidal activity was compared between a bloodstream, AMB-susceptible C. lusitaniae isolate associated with clinical failure and reference C. albicans and Candida glabrata strains. In multivariate analysis, patients having C. lusitaniae fungemia were more likely to have neutropenia (p=0.001), stem cell transplantation (p=0.014) and to have received prior antifungals (p=0.04). Mutational frequencies at clinically-achievable AMB exposures were 8 x 10(5) for C. lusitaniae and <1 x 10(9) for C. albicans and C. glabrata reference strains. Compared to C. albicans and C. glabrata, AMB had much less fungicidal activity against C. lusitaniae in time-kill curve analysis. Clinically, C. lusitaniae fungemia was more frequently associated with stem cell transplant and neutropenia. C. lusitaniae, even originally susceptible to AMB, might be less amenable to AMB therapy.

摘要

葡萄牙念珠菌是一种常对两性霉素B(AMB)耐药的念珠菌属,是念珠菌血症的罕见病因。与白色念珠菌相比,这种体外耐药表型的临床意义、葡萄牙念珠菌菌血症的危险因素及临床表现尚未完全明确。我们回顾了13例癌症患者的连续性葡萄牙念珠菌菌血症病例,并与41例连续性白色念珠菌菌血症病例(1990 - 2004年)进行比较。对一株与临床治疗失败相关的血流中对AMB敏感的葡萄牙念珠菌分离株以及白色念珠菌和光滑念珠菌参考菌株,比较其AMB突变频率和杀菌活性率。多因素分析显示,患有葡萄牙念珠菌菌血症的患者更易出现中性粒细胞减少(p = 0.001)、接受干细胞移植(p = 0.014)以及曾接受过抗真菌治疗(p = 0.04)。在临床可达到的AMB暴露水平下,葡萄牙念珠菌的突变频率为8×10⁵,而白色念珠菌和光滑念珠菌参考菌株的突变频率<1×10⁹。在时间 - 杀菌曲线分析中,与白色念珠菌和光滑念珠菌相比,AMB对葡萄牙念珠菌的杀菌活性要低得多。临床上,葡萄牙念珠菌菌血症更常与干细胞移植和中性粒细胞减少相关。葡萄牙念珠菌即使最初对AMB敏感,可能也较难接受AMB治疗。

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