Shorr Andrew F, Jones Mark E, Friedmann Silke, Ionescu Daniel, Saulay Mikael, Smart Jennifer I, Engelhardt Marc
Pulmonary and Critical Care Medicine, Medstar Washington Hospital, Washington, Columbia, United States of America.
Basilea Pharmaceutica International Ltd, Allschwil, Switzerland.
PLoS One. 2025 Jun 24;20(6):e0326758. doi: 10.1371/journal.pone.0326758. eCollection 2025.
Ceftobiprole is an advanced-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus, resistant pneumococci, and Enterobacterales. In a Phase 3 study in community-acquired bacterial pneumonia (CABP) performed prior to the current US Food and Drug Administration (FDA) guidance, clinical cure at the test-of-cure visit (TOC) was the primary endpoint. We present a re-analysis using early clinical success as the primary endpoint per the 2020 FDA CABP Guidance.
In this multicenter, double-blind study, patients with CABP requiring hospitalization were randomized to intravenous ceftobiprole (500 mg q8h) or ceftriaxone (2000 mg q24h) ± linezolid (600 mg q12h) for 3-14 days. The primary endpoint was clinical success at Day 3 (improvement in ≥2 symptoms of chest pain, cough, productive sputum, difficulty breathing). A 12.5% non-inferiority margin was used.
Of the original 638 patients, 618 (97%) had ≥ 2 symptoms and were included in the Day 3 Intent-to-Treat (ITT) population for the re-analysis. The Day 3 modified ITT population consisted of 187 patients (29%) meeting additional FDA Guidance including Patient Outcomes Research Team (PORT) classification ≥III. Ceftobiprole was non-inferior to ceftriaxone for clinical success for Day 3 ITT (71.0% vs 71.1%) and Day 3 modified ITT (71.1% vs 66.7%) populations. The 28-day all-cause mortality was 1.6% (ceftobiprole) vs 2.6% (ceftriaxone) in the Day 3 ITT population and 2.1% vs 7.8% in the Day 3 modified ITT population.
Ceftobiprole was non-inferior to ceftriaxone ± linezolid for clinical success at Day 3 according to the current 2020 FDA CABP Guidance.
头孢比普是一种新一代头孢菌素，对耐甲氧西林金黄色葡萄球菌、耐药肺炎球菌和肠杆菌科细菌具有活性。在美国食品药品监督管理局（FDA）当前发布指南之前进行的一项社区获得性细菌性肺炎（CABP）3期研究中，治疗结束访视（TOC）时的临床治愈是主要终点。我们根据2020年FDA的CABP指南，以早期临床成功作为主要终点进行了重新分析。
在这项多中心、双盲研究中，需要住院治疗的CABP患者被随机分为静脉注射头孢比普（500mg，每8小时一次）或头孢曲松（2000mg，每24小时一次）±利奈唑胺（600mg，每12小时一次），疗程为3 - 14天。主要终点是第3天的临床成功（胸痛、咳嗽、咳痰、呼吸困难等至少2项症状改善）。采用12.5%的非劣效界值。
在最初的638例患者中，618例（97%）有至少2项症状，被纳入第3天意向性治疗（ITT）人群进行重新分析。第3天改良ITT人群由187例患者（29%）组成，符合包括患者预后研究小组（PORT）分类≥III在内的其他FDA指南。对于第3天ITT人群（71.0%对71.1%）和第3天改良ITT人群（71.1%对66.7%），头孢比普在临床成功方面不劣于头孢曲松。在第3天ITT人群中，28天全因死亡率为1.6%（头孢比普）对2.6%（头孢曲松），在第3天改良ITT人群中为2.1%对7.8%。
根据2020年FDA的CABP指南，头孢比普在第3天的临床成功方面不劣于头孢曲松±利奈唑胺。
