Luo Jun, Liu Min, Ai Wen, Zheng Xiaoling, Liu Shaowei, Huang Kuo, Zhang Changlin, Li Qianyuan, Luo Chunhua
The First College of Clinical Medical Science, China Three Gorges University, Yichang, China.
Yichang Central People's Hospital, Yichang, China.
Antimicrob Agents Chemother. 2024 Jun 5;68(6):e0044824. doi: 10.1128/aac.00448-24. Epub 2024 May 14.
Phage-antibiotic combination treatment is a novel noteworthy drug delivery method in anti-infection. In the current study, we have isolated a new phage, pB23, against carbapenem-resistant Acinetobacter baumannii 2023. Synergistic antibacterial effect between phage pB23 and meropenem combination could be more stable, using moderate doses of phage (multiplicity of infection ranging from 0.1 to 1,000) based on results of antibacterial activity. Phage pB23 and meropenem combination could effectively clear mature biofilms and prevent biofilm formation of carbapenem-resistant . Phage pB23 and meropenem combination also has good synergistic antibacterial effects against carbapenem-resistant in different growth phases under static culture conditions. The pig skin explant model shows that phage pB23 and meropenem combination has a synergistic effect to remove bacteria from wounds . Phage pB23 and meropenem combination also exhibited a synergistic antibacterial effect using a zebrafish infection mode. The potential promotion of phage proliferation by meropenem and the sensitivity recovery of phage-resistant bacteria to meropenem might elucidate the mechanism of the synergistic antimicrobial activity. In summary, our study illustrates that phage pB23 and meropenem combination could produce synergistic antibacterial effects against carbapenem-resistant under static growth conditions. This study also demonstrates that phage-antibiotic combination will become an effective strategy to enhance antibacterial activity of individual drug and provide a new idea of the drug development for the treatment of infections due to carbapenem-resistant and other multidrug-resistant bacteria.
噬菌体 - 抗生素联合治疗是抗感染领域一种值得关注的新型药物递送方法。在本研究中,我们分离出了一种针对耐碳青霉烯类鲍曼不动杆菌2023的新型噬菌体pB23。根据抗菌活性结果,使用中等剂量的噬菌体(感染复数范围为0.1至1000)时,噬菌体pB23与美罗培南联合使用的协同抗菌效果可能更稳定。噬菌体pB23与美罗培南联合使用可有效清除成熟生物膜并防止耐碳青霉烯类细菌形成生物膜。在静态培养条件下,噬菌体pB23与美罗培南联合使用对处于不同生长阶段的耐碳青霉烯类细菌也具有良好的协同抗菌效果。猪皮肤外植体模型表明,噬菌体pB23与美罗培南联合使用具有协同作用,可从伤口清除细菌。使用斑马鱼感染模型时,噬菌体pB23与美罗培南联合使用也表现出协同抗菌效果。美罗培南对噬菌体增殖的潜在促进作用以及噬菌体耐药菌对美罗培南敏感性的恢复可能阐明了协同抗菌活性的机制。总之,我们的研究表明,在静态生长条件下,噬菌体pB23与美罗培南联合使用可对耐碳青霉烯类细菌产生协同抗菌效果。本研究还表明,噬菌体 - 抗生素联合使用将成为增强单一药物抗菌活性的有效策略,并为治疗耐碳青霉烯类细菌及其他多重耐药菌引起的感染提供新的药物研发思路。