University of Cincinnati College of Medicine, Cincinnati, Ohio.
Ohio State University School of Medicine, Columbus.
JAMA Surg. 2017 Mar 1;152(3):224-232. doi: 10.1001/jamasurg.2016.4237.
Eravacycline is a novel, fully synthetic fluorocycline antibiotic of the tetracycline class with in vitro activity against clinically important gram-negative, gram-positive aerobic, and facultative bacteria including most of those resistant to cephalosporins, fluoroquinolones, β-lactam/β-lactamase inhibitors, multidrug resistant strains and carbapenem-resistant Enterobacteriaceae, and most anaerobic pathogens.
To evaluate the efficacy and safety of eravacycline compared with ertapenem in adult hospitalized patients with complicated intra-abdominal infections (cIAIs).
DESIGN, SETTING, AND PARTICIPANTS: This was a phase III, randomized, double-blind, multicenter study that evaluated the efficacy and safety of eravacycline in comparison with ertapenem in patients with cIAI requiring surgical or percutaneous intervention. The test-of-cure evaluation was conducted 25 to 31 days after the first dose of the study drug and the follow-up visit was conducted 38 to 50 days after the first dose of the study drug. All patients recruited into this study were hospitalized. Five hundred forty-one patients were recruited for this study; 270 patients were randomized to receive eravacycline, and 271 patients were randomized to receive ertapenem. Patients had to meet all of the following criteria: hospitalized for cIAI requiring intervention; 18 years or older; evidence of systemic inflammatory response; pain caused by cIAI; able to provide informed consent; and diagnosis of cIAI with sonogram or radiographic imaging or visual confirmation. Analyses were done in intent-to-treat and evaluable populations.
Patients received eravacycline, 1.0 mg/kg every 12 hours, or ertapenem, 1.0 g every 24 hours, for a minimum of four 24-hour dosing cycles.
Clinical outcome assessments were made at the end of treatment, test of cure, and follow-up visits and were classified as clinical cure, clinical failure, or indeterminate/missing.
In total, 541 patients were randomly assigned to treatment: 270 in the eravacycline group and 271 in the ertapenem group. The mean ages were 54.9 years and 55.4 years for the eravacycline and ertapenem groups, respectively. Most patients were white (263 of 270 patients [97.4%] in the eravacycline group and 260 of 271 patients [95.9%] in the ertapenem group). For the microbiological intent-to-treat population, the rates of clinical cure at the test-of-cure visit were 86.8% in the eravacycline group and 87.6% in the ertapenem group. The difference in clinical cure rates between the groups was -0.80% (95% CI, -7.1% to 5.5%), meeting the prespecified noninferiority margin and allowing for statistical noninferiority of eravacycline to ertapenem to be declared for this study. Both study drugs were well tolerated.
Overall, eravacycline demonstrated noninferiority to ertapenem for the treatment of patients with cIAI.
Clinicaltrials.gov Identifier: NCT01844856.
依拉环素是一种新型的全合成氟环素类四环素类抗生素，具有体外活性，可对抗临床重要的革兰氏阴性、革兰氏阳性需氧菌和兼性细菌，包括大多数对头孢菌素、氟喹诺酮类、β-内酰胺/β-内酰胺酶抑制剂、多药耐药株和碳青霉烯类耐药肠杆菌科以及大多数厌氧菌病原体耐药的细菌。
评估依拉环素与厄他培南在住院治疗复杂性腹腔内感染（cIAI）患者中的疗效和安全性。
设计、地点和参与者：这是一项 III 期、随机、双盲、多中心研究，评估了依拉环素与厄他培南在需要手术或经皮干预的 cIAI 患者中的疗效和安全性。治疗后评估在研究药物首剂后 25 至 31 天进行，随访在研究药物首剂后 38 至 50 天进行。所有纳入本研究的患者均住院治疗。本研究共招募了 541 名患者；270 名患者随机接受依拉环素治疗，271 名患者随机接受厄他培南治疗。患者必须符合以下所有标准：因 cIAI 住院需要干预；年龄 18 岁或以上；有全身炎症反应的证据；因 cIAI 而感到疼痛；能够提供知情同意；诊断为 cIAI，有 sonogram 或放射影像学或视觉确认。分析在意向治疗和可评估人群中进行。
患者接受依拉环素，1.0mg/kg，每 12 小时一次，或厄他培南，1.0g，每 24 小时一次，至少接受四个 24 小时给药周期。
在治疗结束时、治疗后评估时和随访时进行临床疗效评估，分类为临床治愈、临床失败或不确定/缺失。
共有 541 名患者被随机分配至治疗组：依拉环素组 270 例，厄他培南组 271 例。依拉环素组和厄他培南组的平均年龄分别为 54.9 岁和 55.4 岁。大多数患者为白人（依拉环素组 270 例患者中有 263 例[97.4%]，厄他培南组 271 例患者中有 260 例[95.9%]）。在微生物学意向治疗人群中，治疗后评估时依拉环素组的临床治愈率为 86.8%，厄他培南组为 87.6%。两组间临床治愈率的差异为-0.80%（95%CI，-7.1%至 5.5%），符合预设的非劣效性边界，允许宣布依拉环素在本研究中对厄他培南具有非劣效性。两种研究药物均具有良好的耐受性。
总体而言，依拉环素在治疗复杂性腹腔内感染患者方面显示出与厄他培南非劣效性。
ClinicalTrials.gov 标识符：NCT01844856。
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