Goodman J L, Winston D J, Greenfield R A, Chandrasekar P H, Fox B, Kaizer H, Shadduck R K, Shea T C, Stiff P, Friedman D J
University of Minnesota Hospital and Clinics, Minneapolis.
N Engl J Med. 1992 Mar 26;326(13):845-51. doi: 10.1056/NEJM199203263261301.
Superficial and systemic fungal infections are a major problem among severely immunocompromised patients who undergo bone marrow transplantation. We performed a double-blind, randomized, multicenter trial in which patients receiving bone marrow transplants were randomly assigned to receive placebo or fluconazole (400 mg daily). Fluconazole or placebo was administered prophylactically from the start of the conditioning regimen until the neutrophil count returned to 1000 per microliter, toxicity was suspected, or a systemic fungal infection was suspected or proved.
By the end of the treatment period, 67.2 percent of the 177 patients assigned to placebo had a positive fungal culture of specimens from any site, as compared with 29.6 percent of the 179 patients assigned to fluconazole. Among these, superficial infections were diagnosed in 33.3 percent of the patients receiving placebo and in 8.4 percent of the patients receiving fluconazole (P less than 0.001). Systemic fungal infections occurred in 28 patients who received placebo as compared with 5 who received fluconazole (15.8 percent vs. 2.8 percent, P less than 0.001). Fluconazole prevented infection with all strains of candida except Candida krusei. Fluconazole was well tolerated, although patients who received it had a higher mean increase in alanine aminotransferase levels than patients who received placebo. Although there was no significant difference in overall mortality between the groups, fewer deaths were ascribed to acute systemic fungal infections in the group receiving fluconazole than in the group receiving placebo (1 of 179 vs. 10 of 177, P less than 0.001).
Prophylactic administration of fluconazole to recipients of bone marrow transplants reduces the incidence of both systemic and superficial fungal infections.
对于接受骨髓移植的严重免疫功能低下患者，浅表和全身性真菌感染是一个主要问题。我们进行了一项双盲、随机、多中心试验，将接受骨髓移植的患者随机分为两组，分别接受安慰剂或氟康唑（每日400毫克）治疗。从预处理方案开始至中性粒细胞计数恢复至每微升1000个、怀疑出现毒性反应或怀疑或证实发生全身性真菌感染期间，预防性给予氟康唑或安慰剂。
到治疗期结束时，177例分配接受安慰剂治疗的患者中，67.2%的患者任何部位标本的真菌培养呈阳性，而分配接受氟康唑治疗的179例患者中这一比例为29.6%。其中，接受安慰剂治疗的患者中有33.3%被诊断为浅表感染，接受氟康唑治疗的患者中这一比例为8.4%（P<0.001）。接受安慰剂治疗的28例患者发生了全身性真菌感染，而接受氟康唑治疗的患者中有5例发生（15.8%对2.8%，P<0.001）。氟康唑可预防除克鲁斯念珠菌外的所有念珠菌菌株感染。氟康唑耐受性良好，尽管接受该药治疗的患者丙氨酸转氨酶水平的平均升高幅度高于接受安慰剂治疗的患者。尽管两组的总死亡率无显著差异，但接受氟康唑治疗组因急性全身性真菌感染导致的死亡人数少于接受安慰剂治疗组（179例中的1例对177例中的10例，P<0.001）。
对骨髓移植受者预防性给予氟康唑可降低全身性和浅表性真菌感染的发生率。
