头孢托罗匹酯治疗复杂菌血症。
Ceftobiprole for Treatment of Complicated Bacteremia.
机构信息
From the Division of Infectious Diseases, Duke University (T.L.H., N.A.T., V.G.F.), and Duke Clinical Research Institute (T.L.H., V.G.F.) - both in Durham, NC; the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore (S.E.C.); the Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco (S.B.D.); the Division of Infectious Diseases, Department of Medicine, Denver Health, Denver (T.C.J.); Tufts Medicine and Tufts University School of Medicine, Boston (H.W.B.); Zaycev V.T. Institute of General and Emergency Surgery of the National Academy of Medical Sciences of Ukraine, Kharkiv (O.P.), Regional Clinical Hospital, Ivano-Frankivsk Regional Council, Ivano-Frankivsk (I.T.), and Dnipropetrovsk I.I. Mechnikov Regional Clinical Hospital, Dnipro (S.K.) - all in Ukraine; Eurohospital Plovdiv, Plovdiv (B.A.), and University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov," Clinic of Purulent-Septic Surgery, Sofia (I.P.) - both in Bulgaria; LTD Academician Vakhtang Bochorishvili Clinic, Tbilisi, Georgia (M.M.); N.I. Pirogov City Clinical Hospital No. 1, Moscow (A.A.); the Department of Medicine and Division of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas, Buenos Aires (M.E.S.); Basilea Pharmaceutica International, Allschwil, Switzerland (M.A.G., M.E., K.H., D.I., M.J., M.S., J.S.); and the Institute for Medical Microbiology, Immunology, and Hygiene, Medical Faculty and University Hospital Cologne, University of Cologne, and the German Center for Infection Research, Partner Site Bonn-Cologne - both in Cologne, Germany (H.S.).
出版信息
N Engl J Med. 2023 Oct 12;389(15):1390-1401. doi: 10.1056/NEJMoa2300220. Epub 2023 Sep 27.
BACKGROUND
Ceftobiprole is a cephalosporin that may be effective for treating complicated bacteremia, including methicillin-resistant .
METHODS
In this phase 3, double-blind, double-dummy, noninferiority trial, adults with complicated bacteremia were randomly assigned in a 1:1 ratio to receive ceftobiprole at a dose of 500 mg intravenously every 6 hours for 8 days and every 8 hours thereafter, or daptomycin at a dose of 6 to 10 mg per kilogram of body weight intravenously every 24 hours plus optional aztreonam (at the discretion of the trial-site investigators). The primary outcome, overall treatment success 70 days after randomization (defined as survival, bacteremia clearance, symptom improvement, no new bacteremia-related complications, and no receipt of other potentially effective antibiotics), with a noninferiority margin of 15%, was adjudicated by a data review committee whose members were unaware of the trial-group assignments. Safety was also assessed.
RESULTS
Of 390 patients who underwent randomization, 387 (189 in the ceftobiprole group and 198 in the daptomycin group) had confirmed bacteremia and received ceftobiprole or daptomycin (modified intention-to-treat population). A total of 132 of 189 patients (69.8%) in the ceftobiprole group and 136 of 198 patients (68.7%) in the daptomycin group had overall treatment success (adjusted difference, 2.0 percentage points; 95% confidence interval [CI], -7.1 to 11.1). Findings appeared to be consistent between the ceftobiprole and daptomycin groups in key subgroups and with respect to secondary outcomes, including mortality (9.0% and 9.1%, respectively; 95% CI, -6.2 to 5.2) and the percentage of patients with microbiologic eradication (82.0% and 77.3%; 95% CI, -2.9 to 13.0). Adverse events were reported in 121 of 191 patients (63.4%) who received ceftobiprole and 117 of 198 patients (59.1%) who received daptomycin; serious adverse events were reported in 36 patients (18.8%) and 45 patients (22.7%), respectively. Gastrointestinal adverse events (primarily mild nausea) were more frequent with ceftobiprole.
CONCLUSIONS
Ceftobiprole was noninferior to daptomycin with respect to overall treatment success in patients with complicated bacteremia. (Funded by Basilea Pharmaceutica International and the U.S. Department of Health and Human Services; ERADICATE ClinicalTrials.gov number, NCT03138733.).
背景
头孢洛林是一种头孢菌素，可能对治疗包括耐甲氧西林的复杂菌血症有效。
方法
在这项 3 期、双盲、双模拟、非劣效性试验中，患有复杂菌血症的成年人以 1:1 的比例随机分配，接受头孢洛林 500mg 静脉注射，每 6 小时一次，持续 8 天，此后每 8 小时一次，或达托霉素 6 至 10mg/kg 体重静脉注射，每 24 小时一次，加可选的氨曲南（由试验现场研究人员决定）。主要结局为随机分组后 70 天的总体治疗成功率（定义为存活、菌血症清除、症状改善、无新发与菌血症相关的并发症、未接受其他潜在有效抗生素），非劣效性边界为 15%，由数据审查委员会裁定，该委员会成员不了解试验组的分配情况。还评估了安全性。
结果
在 390 名接受随机分组的患者中，有 387 名（头孢洛林组 189 名，达托霉素组 198 名）患有确诊的菌血症并接受了头孢洛林或达托霉素治疗（意向治疗人群）。头孢洛林组 189 名患者中有 132 名（69.8%）和达托霉素组 198 名患者中有 136 名（68.7%）患者总体治疗成功（调整差异为 2.0%，95%置信区间[CI]为-7.1%至 11.1%）。在关键亚组和次要结局方面，头孢洛林组和达托霉素组的结果似乎一致，包括死亡率（分别为 9.0%和 9.1%，95%CI为-6.2%至 5.2%）和微生物清除率（分别为 82.0%和 77.3%，95%CI为-2.9%至 13.0%）。接受头孢洛林的 191 名患者中有 121 名（63.4%）和接受达托霉素的 198 名患者中有 117 名（59.1%）报告了不良事件；36 名患者（18.8%）和 45 名患者（22.7%）报告了严重不良事件。接受头孢洛林治疗的患者更常出现胃肠道不良事件（主要为轻度恶心）。
结论
头孢洛林在治疗复杂菌血症患者方面非劣效于达托霉素。（由 Basilea Pharmaceutica International 和美国卫生与公众服务部资助；ERADICATE ClinicalTrials.gov 编号，NCT03138733。）
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