Dalle Frédéric, Lafon Ingrid, L'ollivier Coralie, Ferrant Emmanuelle, Sicard Pierre, Labruère Catherine, Jebrane Ahmed, Laubriet Aline, Vagner Odile, Caillot Denis, Bonnin Alain
Laboratoire de Parasitologie Mycologie, Hôpital du Bocage, BP 77 908, 21079 Dijon Cedex, France.
Haematologica. 2008 Apr;93(4):581-7. doi: 10.3324/haematol.11882. Epub 2008 Mar 5.
Genotyping studies have shown heterogeneity of Candida albicans flora in patients with human immunodeficiency virus infection, with possible co-existence of multiple clones with distinct resistance patterns. We report the result of a prospective study aimed at investigating the dynamics and heterogeneity of C. albicans flora in patients with de novo acute leukemia.
Between 2001 and 2003, 66 consecutive adults with newly diagnosed acute leukemia were monitored for Candida colonization. From 19 patients with repeated multi-site C. albicans colonization, eight were randomly selected and multiple isolates from each individual mucosal site were genotyped sequentially over time using microsatellite markers.
Despite topical use of polyenes, 60.6% of the patients were colonized repeatedly and at multiple sites. Altogether, 2,730 peripheral samples were cultured, 379 (13.9%) of which yielded yeasts. C. albicans was the most common species recovered (68%). From eight randomly selected patients colonized with C. albicans, 429 isolates were genotyped. Seven patients carried a unique genotype which was identical in all body niches and over the period of study. In one case, minor genotypic differences were observed. None of the patients shared C. albicans clones with identical genotypic profiles. Candidemia occurred in one of eight patients and the blood strain genotype did not differ from those of colonizing isolates. The genotypic profile was not altered by topical and/or systemic use of antifungal agents in any of the patients.
In patients with de novo acute leukemia, genetic evolution of the colonizing C. albicans flora and selection of variants or replacement of the original strain upon antifungal drug pressure or nosocomial transmission are rare events.
基因分型研究表明，人类免疫缺陷病毒感染患者的白色念珠菌菌群存在异质性，可能同时存在多个具有不同耐药模式的克隆。我们报告了一项前瞻性研究的结果，该研究旨在调查初发急性白血病患者白色念珠菌菌群的动态变化和异质性。
在2001年至2003年期间，对66例新诊断的急性白血病成年患者进行了念珠菌定植监测。从19例反复出现多部位白色念珠菌定植的患者中随机选取8例，使用微卫星标记对每个个体黏膜部位的多个分离株随时间进行基因分型。
尽管局部使用了多烯类药物，但60.6%的患者反复出现多部位定植。共培养了2730份外周样本，其中379份（13.9%）培养出酵母菌。白色念珠菌是最常见的分离菌种（68%）。对8例随机选取的白色念珠菌定植患者的429株分离株进行了基因分型。7例患者携带单一基因型，在所有身体部位以及研究期间均相同。在1例患者中观察到了微小的基因型差异。没有患者共享基因型相同的白色念珠菌克隆。8例患者中有1例发生了念珠菌血症，血行菌株的基因型与定植分离株的基因型没有差异。在任何患者中，局部和/或全身使用抗真菌药物均未改变基因型谱。
在初发急性白血病患者中，定植的白色念珠菌菌群的基因进化以及在抗真菌药物压力或医院内传播情况下变异株的选择或原始菌株的替代是罕见事件。
