Pachl Jan, Svoboda Petr, Jacobs Frédérique, Vandewoude Koenraad, van der Hoven Ben, Spronk Peter, Masterson Gary, Malbrain Manu, Aoun Mickael, Garbino Jorge, Takala Jukka, Drgona Lubos, Burnie James, Matthews Ruth
Charles University, Prague, Czech Republic.
Clin Infect Dis. 2006 May 15;42(10):1404-13. doi: 10.1086/503428. Epub 2006 Apr 12.
Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species.
A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10.
Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P<.001). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P<.001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P<.001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated.
Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.
Mycograb（NeuTec制药公司）是一种针对热休克蛋白90的人重组单克隆抗体，在实验室研究中发现它与两性霉素B对多种念珠菌具有协同作用。
开展了一项双盲随机研究，以确定在培养确诊的侵袭性念珠菌病患者中，脂质体两性霉素B联合Mycograb是否优于两性霉素B联合安慰剂。患者接受脂质体两性霉素B制剂加5天疗程的Mycograb或安慰剂治疗，根据念珠菌种类（白色念珠菌与非白色念珠菌）进行分层。纳入标准包括试验开始时存在活动性感染的临床证据，以及在研究治疗开始后3天内从具有临床意义的部位采集的标本培养出念珠菌。主要疗效变量为第10天时对治疗的总体反应（临床和真菌学缓解）。
在来自欧洲和美国的139例入组患者中，117例被纳入改良意向性治疗人群。两性霉素B组61例患者中有29例（48%）在第10天时获得完全总体缓解，而Mycograb联合治疗组56例患者中有47例（84%）获得完全总体缓解（优势比[OR]为5.8；95%置信区间[CI]为2.41 - 13.79；P <.001）。还满足以下疗效标准：临床反应（52%对86%；OR为5.4；95% CI为2.21 - 13.39；P <.001）、真菌学反应（54%对89%；OR为7.1；95% CI为2.64 - 18.94；P <.001）、念珠菌所致死亡率（18%对4%；OR为0.2；95% CI为0.04 - 0.80；P =.025）以及培养确诊的感染清除率（风险比为2.3；95% CI为1.4 - 3.8；P =.001）。Mycograb耐受性良好。
Mycograb联合脂质体两性霉素B可使侵袭性念珠菌病患者的临床和培养确诊结局得到显著改善。
