Anastassopoulou Cleo, Ferous Stefanos, Petsimeri Aikaterini, Gioula Georgia, Tsakris Athanasios
Department of Microbiology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Department of Microbiology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Pathogens. 2024 Oct 14;13(10):896. doi: 10.3390/pathogens13100896.
The continued rise in antimicrobial resistance poses a serious threat to public health worldwide. The use of phages that can have bactericidal activity without disrupting the normal flora represents a promising alternative treatment method. This practice has been successfully applied for decades, mainly in Eastern Europe, and has recently been used as an emergency therapy for compassionate care in the United States. Here, we provide a comprehensive review of the pre-clinical and clinical applications of phage therapy concerning three major Gram-negative pathogens: , , and . The advantages and the challenges of expanding the usage of phages as an alternative or adjunctive treatment for antimicrobial-resistant bacterial infections are discussed. We emphasize the virologic complexities of using the highly adaptable phage populations as molecular tools, along with antibiotic chemical compounds, to effectively combat rapidly coevolving pathogenic bacteria in the host microenvironment. Pre-clinical studies, isolated clinical reports and a few randomized clinical trials have shown that bacteriophages can be effective in treating multidrug-resistant bacterial infections. The ability of some phages to revert the resistance against antibiotics, and possibly also against the human complement and other phages, appears to be a great advantage of phage therapy despite the inevitable emergence of phage-resistant strains. Bacteriophages (or specific phage-derived products) can enhance antimicrobial efficacy by reducing bacterial virulence via the alteration of basic bacterial structures, primarily of the cellular wall and membrane. Although several issues remain open regarding their effective clinical application, it appears that phage-based therapeutics in combination with antibiotics can provide an effective solution to the spread of antimicrobial resistance.
抗菌耐药性的持续上升对全球公共卫生构成了严重威胁。使用具有杀菌活性且不破坏正常菌群的噬菌体代表了一种有前景的替代治疗方法。这种做法已经成功应用了数十年，主要在东欧，最近在美国也被用作同情用药的紧急疗法。在此，我们对噬菌体疗法针对三种主要革兰氏阴性病原体（ 、 和 ）的临床前和临床应用进行了全面综述。讨论了扩大噬菌体作为抗微生物耐药细菌感染的替代或辅助治疗方法使用的优势和挑战。我们强调了将高度适应性的噬菌体群体作为分子工具与抗生素化合物一起用于有效对抗宿主微环境中快速共同进化的病原菌时的病毒学复杂性。临床前研究、个别临床报告和一些随机临床试验表明，噬菌体可有效治疗多重耐药细菌感染。尽管不可避免地会出现噬菌体抗性菌株，但一些噬菌体能够恢复对抗生素以及可能对人类补体和其他噬菌体的抗性，这似乎是噬菌体疗法的一大优势。噬菌体（或特定的噬菌体衍生产品）可通过改变主要是细胞壁和细胞膜的基本细菌结构来降低细菌毒力，从而提高抗菌效果。尽管它们的有效临床应用仍有几个问题有待解决，但基于噬菌体的疗法与抗生素联合使用似乎可以为抗微生物耐药性的传播提供有效的解决方案。
