Division of Infectious Diseases and Department of Pharmacy, Brigham and Women's Hospital, Boston, Massachusetts 02115-6110, USA.
Clin Ther. 2010 Apr;32(4):637-48. doi: 10.1016/j.clinthera.2010.04.005.
Caspofungin is approved in the United States for empiric antifungal therapy for persistent febrile neutropenia (FN). There are limited data about the use of other echinocandins in this setting.
After a formulary change, we retrospectively evaluated the safety and effectiveness of caspofungin and micafungin as empiric antifungal therapy for FN at Brigham and Women's Hospital (Boston, Massachusetts).
This was a retrospective, observational, sequential cohort study. We identified patients who had received >or=2 doses on concurrent days of either caspofungin (between November 2005 and October 2006) or micafungin (between November 2006 and October 2007) for empiric FN therapy. Patients were included for analysis if they were neutropenic (absolute neutrophil count <500 cells/microL) and febrile (temperature >or=100.5 degrees F [>or=38 degrees C]). Patients without previous exposure to an echinocandin were included; those included in the caspofungin cohort were excluded from the micafungin cohort. Those who had previously received another systemic antifungal agent for FN therapy (except fluconazole for mucosal candidiasis) were excluded. Patients were followed through hospital discharge. Outcomes analyzed were successful treatment of baseline invasive fungal disease (IFD), incidence of breakthrough IFD, overall mortality, and discontinuation because of adverse events (AEs). IFD was diagnosed and classified according to current European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group Consensus Group criteria.
Three hundred twenty-three patients met inclusion criteria (caspofungin, n = 149; micafungin, n = 174). Median age was 49 years in both the caspofungin and micafungin groups; 80 (53.7%) and 99 (56.9%) patients in each group, respectively, were men. Fluconazole prophylaxis had been administered to 30 patients (20.1%) treated with caspofungin and 21 patients (12.1%) treated with micafungin. Caspofungin was administered at 70 mg for one dose, followed by 50 mg daily; micafungin was administered at 100 mg daily. The median duration of therapy and of hospitalization were 10 days and 29 days, respectively, with caspofungin, and 9 days and 28 days with micafungin (both, P = NS between groups). Twelve patients (8.1%) in the caspofungin cohort and 13 (7.5%) in the micafungin cohort died during the study period (P = NS). There were 3 cases (2.0%) of baseline IFD in the caspofungin cohort and 6 (3.4%) in the micafungin cohort (P = NS); 6 were successfully treated (caspofungin, 2 [1.3% of entire group]; micafungin, 4 [2.37% of entire group]; P = NS). Breakthrough IFD was diagnosed in 16 patients (10.7%) receiving caspofungin and 21 (12.1%) receiving micafungin (P = NS). AEs requiring echinocandin discontinuation were uncommon (caspofungin, 2 cases of rash and 1 anaphylactoid infusion reaction [2.0%]; mica-fungin, 1 liver function test elevation >or=5 times the upper limit of normal and 1 maculopapular rash [1.1%]; P = NS).
Micafungin, as empiric antifungal therapy for persistent FN, did not appear to differ significantly from caspofungin in terms of safety profile or efficacy in the adult patients included in this sequential cohort analysis at one institution. ClinicalTrials.gov identifier: NCT00723073.
卡泊芬净在美国被批准用于持续发热性中性粒细胞减少症（FN）的经验性抗真菌治疗。关于其他棘白菌素类药物在这种情况下的使用，数据有限。
在药品目录更改后，我们回顾性评估了卡泊芬净和米卡芬净作为发热性中性粒细胞减少症经验性抗真菌治疗在布莱根妇女医院（马萨诸塞州波士顿）的安全性和有效性。
这是一项回顾性、观察性、连续队列研究。我们确定了在 2005 年 11 月至 2006 年 10 月期间同时接受卡泊芬净（≥2 剂，每日剂量）或 2006 年 11 月至 2007 年 10 月期间米卡芬净（≥2 剂，每日剂量）经验性 FN 治疗的患者。如果患者中性粒细胞减少（绝对中性粒细胞计数<500 细胞/μL）和发热（体温≥100.5°F[≥38°C]），则纳入分析。患者无棘白菌素类药物既往暴露史；卡泊芬净组中排除了接受过该药治疗的患者。那些之前接受过另一种全身抗真菌药物治疗 FN 的患者（除了用于黏膜念珠菌病的氟康唑）被排除在外。那些因不良反应（AE）而停止治疗的患者也被排除在外。患者一直随访至出院。分析的结果是基础侵袭性真菌感染（IFI）的成功治疗、IFI 突破、总体死亡率和因 AE 而停药。IFI 根据欧洲癌症研究和治疗组织/侵袭性真菌感染合作组和美国国家过敏和传染病研究所真菌病研究组共识标准进行诊断和分类。
323 名患者符合纳入标准（卡泊芬净组，n=149；米卡芬净组，n=174）。卡泊芬净组和米卡芬净组患者的中位年龄分别为 49 岁，其中分别有 80（53.7%）和 99（56.9%）名男性。30 名患者（20.1%）接受卡泊芬净治疗，21 名患者（12.1%）接受米卡芬净治疗，均接受氟康唑预防治疗。卡泊芬净的起始剂量为 70 mg，随后每日 50 mg；米卡芬净每日 100 mg。卡泊芬净组的中位治疗持续时间和住院时间分别为 10 天和 29 天，米卡芬净组分别为 9 天和 28 天（均 P=NS）。在研究期间，卡泊芬净组中有 12 名（8.1%）患者和米卡芬净组中有 13 名（7.5%）患者死亡（P=NS）。卡泊芬净组中有 3 例（2.0%）基线 IFI，米卡芬净组中有 6 例（3.4%）（P=NS）；6 例患者成功治疗（卡泊芬净组 2 例[整个组的 1.3%]；米卡芬净组 4 例[整个组的 2.37%]；P=NS）。卡泊芬净组中有 16 名（10.7%）患者和米卡芬净组中有 21 名（12.1%）患者诊断为IFI 突破（P=NS）。需要停止使用棘白菌素的 AE 并不常见（卡泊芬净组有 2 例皮疹和 1 例过敏样输液反应[2.0%]；米卡芬净组有 1 例肝功能试验升高>5 倍正常值上限和 1 例斑丘疹皮疹[1.1%]；P=NS）。
在这项单机构连续队列分析中，米卡芬净作为持续性 FN 的经验性抗真菌治疗，在安全性和疗效方面似乎与卡泊芬净没有显著差异。临床试验注册号：NCT00723073。
