Rex J H, Bennett J E, Sugar A M, Pappas P G, van der Horst C M, Edwards J E, Washburn R G, Scheld W M, Karchmer A W, Dine A P
University of Texas Medical School at Houston 77030.
N Engl J Med. 1994 Nov 17;331(20):1325-30. doi: 10.1056/NEJM199411173312001.
Amphotericin B has long been the standard treatment for candidemia, but its use is complicated by its toxicity. More recently, fluconazole, a water-soluble triazole with activity against candida species and little toxicity, has become available. We conducted a multicenter randomized trial that compared amphotericin B with fluconazole as treatment for candidemia.
To be eligible, patients had to have a positive blood culture for candida species, a neutrophil count > or = 500 per cubic millimeter, and no major immunodeficiency. Patients were randomly assigned to receive either amphotericin B (0.5 to 0.6 mg per kilogram of body weight per day) or fluconazole (400 mg per day), each continued for at least 14 days after the last positive blood culture. Outcomes were assessed by a group of investigators blinded to treatment assignment.
Of the 237 patients enrolled, 206 met all entry criteria. The most common diagnoses were renal failure, nonhematologic cancer, and gastrointestinal disease. There was no statistically significant difference in outcome: of the 103 patients treated with amphotericin B, 81 (79 percent) were judged to have been treated successfully, as were 72 of the 103 patients treated with fluconazole (70 percent P = 0.22; 95 percent confidence interval for the difference, -5 to 23 percent). The bloodstream infection failed to clear in 12 patients in the amphotericin group and 15 in the fluconazole group; the species most commonly associated with failure was Candida albicans. There were 41 deaths in the amphotericin group and 34 deaths in the fluconazole group (P = 0.20). Intravascular catheters appeared to be the most frequent source of candidemia. There was less toxicity with fluconazole than with amphotericin B.
In patients without neutropenia and without major immunodeficiency, fluconazole and amphotericin B are not significantly different in their effectiveness in treating candidemia.
两性霉素B长期以来一直是念珠菌血症的标准治疗药物，但其使用因毒性而变得复杂。最近，氟康唑这种对念珠菌有活性且毒性小的水溶性三唑类药物已可供使用。我们进行了一项多中心随机试验，比较两性霉素B与氟康唑治疗念珠菌血症的效果。
符合条件的患者必须血培养念珠菌属阳性、中性粒细胞计数≥每立方毫米500且无严重免疫缺陷。患者被随机分配接受两性霉素B（每日每千克体重0.5至0.6毫克）或氟康唑（每日400毫克），在最后一次血培养阳性后每种药物至少持续使用14天。由对治疗分配不知情的一组研究人员评估结果。
在纳入的237例患者中，206例符合所有入选标准。最常见的诊断是肾衰竭、非血液系统癌症和胃肠道疾病。结果无统计学显著差异：在接受两性霉素B治疗的103例患者中，81例（79%）被判定治疗成功，在接受氟康唑治疗的103例患者中，72例（70%）治疗成功（P = 0.22；差异的95%置信区间为-5%至23%）。两性霉素组有12例患者血流感染未清除，氟康唑组有15例；最常与治疗失败相关的菌种是白色念珠菌。两性霉素组有41例死亡，氟康唑组有34例死亡（P = 0.20）。血管内导管似乎是念珠菌血症最常见的来源。氟康唑的毒性低于两性霉素B。
在无中性粒细胞减少且无严重免疫缺陷的患者中，氟康唑和两性霉素B治疗念珠菌血症的有效性无显著差异。
