Tetraphase Pharmaceuticals, Inc., Watertown, Massachusetts, USA.
University of Michigan Hospital, Ann Arbor, Michigan, USA.
Surg Infect (Larchmt). 2021 Jun;22(5):556-561. doi: 10.1089/sur.2020.241. Epub 2020 Nov 17.
Eravacycline is a novel, fully synthetic fluorocycline antibiotic that was evaluated for the treatment of complicated intra-abdominal infections (cIAI) in two phase 3 clinical trials. The objective of this analysis was to evaluate the clinical cure and microbiologic response at the test-of-cure (TOC) visit and the safety of eravacycline in patients with cIAI and baseline bacteremia who received eravacycline versus comparators. Pooled data of patients with bacteremia from the Investigating Gram-Negative Infections Treated with Eravacycline (IGNITE) 1 and IGNITE4 studies were analyzed. All patients were randomly assigned in a one-to-one ratio to receive eravacycline 1 mg/kg intravenously every 12 hours, ertapenem 1 g intravensouly every 24 hours (IGNITE1), or meropenem 1 g intravenously every eight hours (IGNITE4) for four to 14 days. Blood and intra-abdominal samples were collected from all patients at baseline. Clinical outcome and microbiologic eradiation at the TOC visit (28 days after randomization) and safety in the microbiologic-intent-to-treat population (micro-ITT) were assessed. Of 415 patients treated with eravacycline and 431 treated with carbapenem comparators, concurrent bacteremia was identified in 32 (7.7%) and 31 (7.2%) patients, respectively. Demographic and baseline characteristics were similar among treatment groups. In the micro-ITT population, the pooled clinical response at the TOC visit for eravacycline was 28 of 32 (87.5%) and was 24 of 31 (77.0%) for comparators among the subgroup with baseline bacteremia (treatment difference 5.9; 95% confidence interval [CI], -6.5 to 17.4). At TOC, microbiologic eradication of pathogens isolated from blood specimens occurred for 34 of 35 (97.1%) pathogens with eravacycline and 35 of 36 (97.2%) pathogens with comparators. The incidence of adverse events was comparable between treated groups and similar to that observed in the non-bacteremic population. Eravacycline demonstrated a similar clinical outcome and microbiologic eradication rate as comparator carbapenems in patients with cIAI and associated secondary bacteremia. Future clinical trials of cIAI should report outcomes of this important clinical cohort (cIAI with concurrent bacteremia) given their high risk for adverse outcomes.
依拉环素是一种新型全合成氟环素抗生素，在两项 3 期临床试验中评估用于治疗复杂性腹腔内感染（cIAI）。本分析的目的是评估 cIAI 和基线菌血症患者在治疗结束时（TOC）访视时的临床治愈率和微生物学应答，以及接受依拉环素和对照药物治疗的患者的安全性。对革兰氏阴性菌感染治疗用依拉环素（IGNITE）1 期和 IGNITE4 期研究中合并菌血症患者的数据进行了汇总分析。所有患者按 1:1 的比例随机分配，接受依拉环素 1mg/kg 静脉注射，每 12 小时一次，厄他培南 1g 静脉注射，每 24 小时一次（IGNITE1），或美罗培南 1g 静脉注射，每 8 小时一次，持续 4 至 14 天。所有患者在基线时均采集血液和腹腔内样本。在 TOC 访视（随机分组后 28 天）时评估临床结局和微生物学清除率，并在微生物学意向治疗人群（micro-ITT）中评估安全性。在接受依拉环素治疗的 415 例患者和接受碳青霉烯类对照药物治疗的 431 例患者中，分别有 32 例（7.7%）和 31 例（7.2%）患者合并菌血症。治疗组之间的人口统计学和基线特征相似。在 micro-ITT 人群中，依拉环素组 TOC 时的总体临床反应为 28/32（87.5%），菌血症亚组为 24/31（77.0%）（治疗差异 5.9；95%置信区间 [CI]，-6.5 至 17.4）。在 TOC 时，从血液标本中分离出的病原体用依拉环素治疗后有 34/35（97.1%），用对照药物治疗后有 35/36（97.2%）清除。治疗组之间的不良事件发生率相似，与非菌血症人群相似。依拉环素在 cIAI 合并继发性菌血症患者中的临床疗效和微生物学清除率与碳青霉烯类对照药物相似。鉴于 cIAI 合并菌血症患者不良结局风险较高，未来的 cIAI 临床试验应报告这一重要临床队列的结果。
