Wingard J R, Merz W G, Rinaldi M G, Johnson T R, Karp J E, Saral R
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322.
N Engl J Med. 1991 Oct 31;325(18):1274-7. doi: 10.1056/NEJM199110313251803.
In early 1990 fluconazole was introduced as a prophylactic antifungal agent after bone marrow transplantation. During the same year Candida krusei emerged as the chief candida pathogen among patients with bone marrow transplants.
To determine whether there was a correlation between the introduction of fluconazole and the increased incidence of C. krusei, we conducted a retrospective study based on the medical, mycologic, and autopsy records of all adult inpatients who had undergone bone marrow transplantation (n = 296) or who had leukemia (n = 167) at the study center during 1989 and 1990.
The 84 patients who received antifungal prophylaxis with fluconazole had a sevenfold greater frequency of C. krusei infection than the 335 patients who did not receive fluconazole (8.3 percent vs. 1.2 percent, P = 0.002), despite having a lower frequency of disseminated C. albicans and C. tropicalis infections (0 vs. 6.0 percent, P = 0.02). Ten of the 11 C. krusei infections were controlled by a combination of amphotericin B and flucytosine. Colonization by C. krusei was found in 40.5 percent of the patients who received fluconazole but in only 16.7 percent of those who did not receive it (P less than 0.0001). Colonization was independently associated with the prophylactic use of both fluconazole (odds ratio, 3.50; P less than 0.001) and norfloxacin (odds ratio, 2.53; P = 0.04). C. krusei was not susceptible to fluconazole in vitro.
In patients at high risk for disseminated candida infections, suppression of bacterial flora and the more common candida pathogens may permit some less pathogenic, but natively resistant candida species, such as C. krusei, to emerge as systemic pathogens.
1990年初，氟康唑作为骨髓移植后的预防性抗真菌药物被引入。同年，克柔念珠菌成为骨髓移植患者中主要的念珠菌病原体。
为了确定氟康唑的引入与克柔念珠菌发病率增加之间是否存在关联，我们基于1989年和1990年在研究中心接受骨髓移植（n = 296）或患有白血病（n = 167）的所有成年住院患者的医疗、真菌学和尸检记录进行了一项回顾性研究。
接受氟康唑抗真菌预防的84例患者克柔念珠菌感染频率比未接受氟康唑的335例患者高7倍（8.3%对1.2%，P = 0.002），尽管播散性白色念珠菌和热带念珠菌感染频率较低（0对6.0%，P = 0.02）。11例克柔念珠菌感染中有10例通过两性霉素B和氟胞嘧啶联合治疗得到控制。接受氟康唑的患者中有40.5%发现有克柔念珠菌定植，而未接受氟康唑的患者中只有16.7%有定植（P < 0.0001）。定植与氟康唑（比值比，3.50；P < 0.001）和诺氟沙星（比值比，2.53；P = 0.04）的预防性使用独立相关。克柔念珠菌在体外对氟康唑不敏感。
在播散性念珠菌感染高危患者中，抑制细菌菌群和较常见的念珠菌病原体可能会使一些致病性较低但天然耐药的念珠菌物种，如克柔念珠菌，成为系统性病原体。
