Bodmann Klaus-Friedrich, Hagel Stefan, Oliva Alessandra, Kluge Stefan, Mularoni Alessandra, Galfo Valentina, Falcone Marco, Pletz Mathias W, Lindau Simone, Käding Nadja, Kielstein Jan T, Zoller Michael, Tascini Carlo, Kintrup Sebastian, Schädler Dirk, Spies Claudia, De Rosa Francesco G, Radnoti Szilvia, Bandera Alessandra, Luzzati Roberto, Allen Sam, Sarmati Loredana, Cascio Antonio, Kapravelos Nikolaos, Subudhi Chinari P K, Dimopoulos George, Vossen Matthias G, Bal Abhijit M, Venditti Mario, Mastroianni Claudio M, Borrmann Thomas, Mayer Christian
Kliniken Nordoberpfalz AG, Klinikum Weiden, Weiden, Germany.
Institute for Infectious Diseases and Infection Control, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany.
Infect Dis Ther. 2025 Apr;14(4):765-791. doi: 10.1007/s40121-025-01125-2. Epub 2025 Mar 19.
Intravenous fosfomycin (FOS) is a broad-spectrum antibiotic primarily used in combination therapy to treat severe infections caused by both Gram-positive (GP) and Gram-negative (GN) pathogens, including multi-drug resistant (MDR) bacteria. The aim of this study, the largest to date, was to evaluate the effectiveness, safety, usage patterns, and patient characteristics of FOS in a real-world setting.
Interim analysis of an ongoing, prospective, non-interventional, multicentre study in five European countries, involving centres in Germany, Italy, the United Kingdom, Greece, and Austria.
A total of 716 patients were enrolled between January 2017 and November 2023 (mean age: 62.8 years, APACHE II: 18.3, SOFA: 6.7). Main indications for FOS were bacteraemia/sepsis (23.6%), complicated urinary tract infections (18.0%), and bone and joint infections (17.4%). Other indications included hospital-acquired/ventilator-associated pneumonia (11.0%), complicated skin and soft tissue infections (9.1%), bacterial meningitis/central nervous system (CNS) infections (7.8%), and infective endocarditis (6.4%). Most common pathogens identified were Staphylococcus aureus (31.4%, including methicillin-resistant S. aureus), Klebsiella spp. (including K. pneumoniae) (17.2%), Escherichia coli (14.2%), coagulase-negative staphylococci (12.9%), other Enterobacterales (10.9%), and Pseudomonas aeruginosa (8.4%). In 34.6% of patients, an MDR pathogen was involved. Carbapenem resistance (CR) was high in Klebsiella spp. infections (59/123, 48.0%). In most patients, FOS was used in combination therapy (90.2%). The median dose was 15 g/day. Overall, clinical success and clinical response were favourable with 75.3% and 83.4% at the end of FOS treatment. Clinical success rates in infections caused by MDR or CR pathogens were 78.0% and 81.8%, respectively. Microbiological cure was achieved in 82.4% of all patients. Electrolyte imbalances were the most frequently observed adverse drug reactions, while gastrointestinal disorders were rare.
The results from this study suggest that FOS is a safe and effective option as combination partner in the treatment of patients with severe infections caused by both GP and GN pathogens, including deep-seated infections and/or involvement of MDR bacteria.
ClinicalTrials.gov identifier, NCT02979951.
静脉注射磷霉素（FOS）是一种广谱抗生素，主要用于联合治疗由革兰氏阳性（GP）和革兰氏阴性（GN）病原体引起的严重感染，包括多重耐药（MDR）细菌。本研究是迄今为止规模最大的一项研究，旨在评估FOS在实际临床环境中的有效性、安全性、使用模式和患者特征。
对一项正在进行的、前瞻性、非干预性、多中心研究进行中期分析，该研究在五个欧洲国家开展，涉及德国、意大利、英国、希腊和奥地利的研究中心。
2017年1月至2023年11月期间共纳入716例患者（平均年龄：62.8岁，急性生理学与慢性健康状况评分系统II [APACHE II]：18.3，序贯器官衰竭评估 [SOFA]：6.7）。FOS的主要适应证为菌血症/脓毒症（23.6%）、复杂性尿路感染（18.0%）以及骨和关节感染（17.4%）。其他适应证包括医院获得性/呼吸机相关性肺炎（11.0%）、复杂性皮肤和软组织感染（9.1%）、细菌性脑膜炎/中枢神经系统（CNS）感染（7.8%）以及感染性心内膜炎（6.4%）。鉴定出的最常见病原体为金黄色葡萄球菌（31.4%，包括耐甲氧西林金黄色葡萄球菌）、克雷伯菌属（包括肺炎克雷伯菌）（17.2%）、大肠埃希菌（14.2%）、凝固酶阴性葡萄球菌（12.9%）、其他肠杆菌科细菌（10.9%）以及铜绿假单胞菌（8.4%）。34.6%的患者感染了MDR病原体。克雷伯菌属感染中碳青霉烯耐药（CR）率较高（59/123，48.0%）。大多数患者接受了联合治疗（90.2%）。中位剂量为15克/天。总体而言，FOS治疗结束时临床成功率和临床反应良好，分别为75.3%和83.4%。MDR或CR病原体引起的感染的临床成功率分别为78.0%和81.8%。所有患者中82.4%实现了微生物学治愈。电解质失衡是最常观察到的药物不良反应，而胃肠道疾病较为罕见。
本研究结果表明，FOS作为联合用药治疗由GP和GN病原体引起的严重感染患者是一种安全有效的选择，包括深部感染和/或MDR细菌感染。
ClinicalTrials.gov标识符，NCT02979951。
