Piscaglia Marco, Scaglione Giovanni, Genovese Camilla, Borgonovo Fabio, Brivio Fabio, Rampichini Flavia, Grifantini Renata, Bandera Alessandra, Gori Andrea, Colaneri Marta, Palomba Emanuele
Department of Infectious Diseases, Luigi Ospedale Luigi Sacco, University of Milan, Milan, Italy.
Library of Medicine and Surgery, University of Milan, Milan, Italy.
Infect Dis Ther. 2025 Jul 25. doi: 10.1007/s40121-025-01195-2.
The global spread of multidrug-resistant organisms (MDROs), particularly the World Health Organization (WHO) priority pathogens, poses a major challenge to infection treatment, necessitating alternative therapeutic strategies. Monoclonal antibodies (mAbs) have emerged as a potential approach. This review evaluates the clinical efficacy, safety, and limitations of mAbs targeting critical bacterial pathogens, analyzing factors influencing therapeutic outcomes, and proposing strategies to optimize their clinical application.
A comprehensive analysis of clinical trials investigating antibacterial mAbs was conducted. The review assessed key factors influencing therapeutic outcomes, including trial design, patient heterogeneity, and pharmacokinetics (PK). Comparative analysis was performed to examine differences in efficacy, safety, and limitations across studies. A structured risk of bias assessment was performed using Cochrane Methods' tools.
Owing to the low number of studies against MDROs, all trials about mAbs targeting Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) were included, disregarding resistance profiles. Generally, clinical trials evaluating antibacterial mAbs have shown preliminary evidence. For PA, panobacumab exhibited a favorable safety profile but lacked clear clinical benefits, showing a good survival rate but in a small uncontrolled trial. Rivabazumab reduced bacterial colonization, but did not significantly lower pneumonia incidence. Gremubamab was well tolerated but failed to meet efficacy endpoints. For SA, tosatoxumab and suvratoxumab failed to show statistical significance but may have potential benefits for pneumonia, although phase III trials are needed.
Inconsistent efficacy may stem from complex host-pathogen interactions, biofilm formation, and variations in patient immune status. Future trials should investigate early mAb administration, stratified patient selection, and standardized antibiotic coadministration, poorly addressed thus far. Optimized dosing and mAb combination regimens are promising yet unexplored paths, while high production costs and regulatory issues remain a significant barrier.
多重耐药菌（MDROs）的全球传播，尤其是世界卫生组织（WHO）优先关注的病原体，对感染治疗构成了重大挑战，因此需要 alternative therapeutic strategies。单克隆抗体（mAbs）已成为一种潜在的方法。本综述评估了针对关键细菌病原体的单克隆抗体的临床疗效、安全性和局限性，分析了影响治疗结果的因素，并提出了优化其临床应用的策略。
对研究抗菌单克隆抗体的临床试验进行了全面分析。该综述评估了影响治疗结果的关键因素，包括试验设计、患者异质性和药代动力学（PK）。进行了比较分析，以检查各研究在疗效、安全性和局限性方面的差异。使用Cochrane方法的工具进行了结构化的偏倚风险评估。
由于针对MDROs的研究数量较少，所有关于靶向金黄色葡萄球菌（SA）和铜绿假单胞菌（PA）的单克隆抗体的试验均被纳入，而不考虑耐药情况。总体而言，评估抗菌单克隆抗体的临床试验已显示出初步证据。对于PA，泛巴库单抗显示出良好的安全性，但缺乏明确的临床益处，在一项小型非对照试验中显示出良好的生存率。利伐巴单抗减少了细菌定植，但并未显著降低肺炎发病率。格雷穆单抗耐受性良好，但未达到疗效终点。对于SA，托沙妥单抗和苏夫妥单抗未显示出统计学意义，但可能对肺炎有潜在益处，尽管需要进行III期试验。
疗效不一致可能源于复杂的宿主-病原体相互作用、生物膜形成以及患者免疫状态的差异。未来的试验应研究单克隆抗体的早期给药、分层患者选择和标准化抗生素联合使用，这些问题迄今尚未得到充分解决。优化给药方案和单克隆抗体联合治疗方案是有前景但尚未探索过的途径，而高生产成本和监管问题仍然是一个重大障碍。
