DiNubile Mark J, Lupinacci Robert J, Strohmaier Kim M, Sable Carole A, Kartsonis Nicholas A
Department of Medical Communication, Merck Research Laboratories, West Point, PA 19486, USA.
J Crit Care. 2007 Sep;22(3):237-44. doi: 10.1016/j.jcrc.2006.11.004. Epub 2007 Apr 10.
The objectives of this study were to contrast risk factors, microbiology, and outcomes in patients with invasive candidiasis treated in an intensive care unit (ICU) with those in patients with invasive candidiasis treated outside an ICU and to describe therapeutic results with caspofungin in ICU patients.
We retrospectively identified patients with documented invasive candidiasis who received their first dose of the study drug in the ICU as part of a double-blind randomized trial. Participants were not stratified at entry by their ICU status. Patients received caspofungin (50 mg/d after a 70-mg loading dose) or conventional amphotericin B (0.6-1.0 mg/kg per day) for 10 to 14 days. A favorable response required resolution of signs and symptoms as well as eradication of Candida pathogens.
Of the 224 patients, 97 (43%) received their first dose of the study drug in the ICU. Most patients had well-recognized risk factors for invasive candidiasis, including broad-spectrum antibiotics, central venous catheters, and hyperalimentation. Recent surgery was more common whereas malignancy, neutropenia, and immunosuppression were less common among ICU patients than among non-ICU patients. Candidemia was demonstrated in 81% of ICU patients and in 84% of non-ICU patients. Favorable response rates in the ICU patients vs the non-ICU patients were 68% (95% confidence interval [CI] = 53%, 82%) vs 77% (95% CI = 67%, 87%) for caspofungin and 56% (95% CI = 43%, 69%) vs 67% (95% CI = 55%, 79%) for amphotericin B. After accounting for differences in APACHE (Acute Physiology and Chronic Health Evaluation) II score, neutropenia status, and geographic region, we found that patients initiating the study therapy in an ICU were still more likely to die than patients initiating study therapy outside an ICU. For ICU patients, all-cause mortality rates were 45% (95% CI = 30%, 60%) for caspofungin recipients and 40% (95% CI = 28%, 53%) for amphotericin B recipients, whereas candidiasis-attributable mortality rates were 5% (95% CI = 0%, 12%) for caspofungin recipients and 11% (95% CI = 3%, 19%) for amphotericin B recipients. Overall, drug-related adverse events were reported less often among the ICU patients than among the non-ICU patients.
In ICU patients treated with antifungal therapy, invasive candidiasis is associated with substantial mortality, but most deaths cannot be directly attributed to this infection.
本研究的目的是对比在重症监护病房（ICU）接受治疗的侵袭性念珠菌病患者与在ICU以外接受治疗的侵袭性念珠菌病患者的危险因素、微生物学特征及治疗结果，并描述卡泊芬净对ICU患者的治疗效果。
我们回顾性确定了作为双盲随机试验一部分在ICU接受首剂研究药物治疗的确诊侵袭性念珠菌病患者。参与者在入组时未根据其ICU状态进行分层。患者接受卡泊芬净（70mg负荷剂量后50mg/d）或传统两性霉素B（0.6 - 1.0mg/kg/d）治疗10至14天。良好反应要求体征和症状消退以及念珠菌病原体根除。
在224例患者中，97例（43%）在ICU接受首剂研究药物治疗。大多数患者有公认的侵袭性念珠菌病危险因素，包括广谱抗生素、中心静脉导管和胃肠外营养。近期手术在ICU患者中更常见，而恶性肿瘤、中性粒细胞减少和免疫抑制在ICU患者中比在非ICU患者中少见。81%的ICU患者和84%的非ICU患者证实有念珠菌血症。卡泊芬净治疗的ICU患者与非ICU患者的良好反应率分别为68%（95%置信区间[CI]=53%，82%）和77%（95%CI = 67%，87%），两性霉素B治疗的分别为56%（95%CI = 43%，69%）和67%（95%CI = 55%，79%）。在考虑急性生理与慢性健康状况评估（APACHE）II评分、中性粒细胞减少状态和地理区域的差异后，我们发现与在ICU以外开始研究治疗的患者相比，在ICU开始研究治疗的患者死亡可能性仍然更高。对于ICU患者，卡泊芬净接受者的全因死亡率为45%（95%CI = 30%，60%），两性霉素B接受者为40%（95%CI = 28%，53%），而卡泊芬净接受者念珠菌病归因死亡率为5%（95%CI = 0%，12%），两性霉素B接受者为11%（95%CI = 3%，19%）。总体而言，ICU患者中报告的药物相关不良事件比非ICU患者少。
在接受抗真菌治疗的ICU患者中，侵袭性念珠菌病与相当高的死亡率相关，但大多数死亡不能直接归因于这种感染。
