Tängdén Thomas, Carrara Elena, Hellou Mona Mustafa, Yahav Dafna, Paul Mical
Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden.
Division of Infectious Diseases, Department of Diagnostic and Public Health, University of Verona, Verona, Italy.
Clin Microbiol Infect. 2025 Mar;31(3):354-359. doi: 10.1016/j.cmi.2024.09.025. Epub 2024 Oct 5.
Following intense efforts to revive the dry antibiotic research and development pipeline, a few highly awaited antibiotics with activity against multidrug-resistant (MDR) bacteria were recently approved.
We aim to highlight gaps in the evidence generated for new antibiotics by the time of their approval and to review the consequent limitations of treatment guidelines for priority MDR bacteria. We also report on the availability of the new antibiotics, reimbursement strategies allowing the use of these antibiotics in hospitals, and antibiotic stewardship efforts.
We searched PubMed for phase 3 randomized controlled trials, guidelines, and publications on access, usage, regulatory aspects and antimicrobial stewardship of antibiotics approved for use against MDR bacteria between 2013 and 2023. Other sources included governmental and professional documents regarding policies for reimbursement and use of the new antibiotics.
Several gaps in the evidence available regarding the new antibiotics are described related to the trials' target populations, comparators, management algorithm within the trial, non-inferiority hypotheses, and assessment of resistance development within the studies. We highlight the risk of current guidelines to increase the usage of new antibiotics and consequently accelerate resistance development. Updated mapping of antibiotic availability reveals critical inequality in access to the new antibiotics. Finally, strategies used nationally in Europe to provide access to the new antibiotics are not sufficiently balanced by antibiotic stewardship efforts to calibrate the judicious use of the new antibiotics.
Antibiotic resistance is an immediate threat. The present review highlights areas where more systematic and uniform strategies across countries and geographical regions are warranted to improve evidence, availability, and use of new broad-spectrum antibiotics.
在为重振枯竭的抗生素研发渠道付出巨大努力之后，最近有几种备受期待的、对多重耐药（MDR）细菌有活性的抗生素获得批准。
我们旨在强调新抗生素获批时所产生证据中的差距，并审视针对重点MDR细菌的治疗指南随之而来的局限性。我们还报告新抗生素的可及性、允许在医院使用这些抗生素的报销策略以及抗生素管理措施。
我们在PubMed上搜索了2013年至2023年间获批用于治疗MDR细菌的抗生素的3期随机对照试验、指南以及关于其可及性、使用、监管方面和抗菌药物管理的出版物。其他资料来源包括有关新抗生素报销和使用政策的政府文件和专业文件。
描述了关于新抗生素现有证据中的几个差距，涉及试验的目标人群、对照、试验中的管理算法、非劣效性假设以及研究中耐药性发展的评估。我们强调当前指南存在增加新抗生素使用从而加速耐药性发展的风险。更新后的抗生素可及性图谱揭示了获取新抗生素方面的严重不平等。最后，欧洲各国在提供新抗生素可及性方面所采用的策略，在通过抗生素管理措施来校准新抗生素的合理使用方面未达到充分平衡。
抗生素耐药性是一个紧迫的威胁。本综述突出了一些领域，在这些领域需要在国家和地理区域层面采取更系统、统一的策略，以改善新的广谱抗生素的证据、可及性和使用情况。
