Synergistic Mechanisms and Applications of Phage-Antibiotic Combination Therapy
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摘要: 抗生素滥用导致耐药菌迅速增加，细菌感染难以有效控制，对人类健康构成严重威胁。随着抗生素耐药性问题的日益加剧和新抗生素研发滞后，寻找更有效的治疗策略成为全球公共卫生领域的迫切需求。噬菌体作为潜在治疗方案，近年来受到广泛关注，但噬菌体存在宿主范围狭窄、溶源性现象等局限性。噬菌体-抗生素协同作用通过增强噬菌体裂解活性，减少抗生素剂量，显著降低耐药风险，展现出卓越的抗菌效果。综述了噬菌体-抗生素协同作用的机制及研究进展，以期进一步推动噬菌体与抗生素联合疗法的研究与应用，为应对抗生素耐药性问题提供新的解决方案。Abstract: The overuse of antibiotics has led to a rapid increase of antibiotic-resistant bacteria, making bacterial infections difficult to control effectively and posing a serious threat to human health. As antibiotic resistance problems become increasingly severe and the development of new antibiotics lags, finding more effective treatment strategies has become an urgent need in global public health. Bacteriophages, as a potential therapeutic option, have attracted increasing attention in recent years; however, bacteriophages have limitations such as a narrow host range and lysogeny. Synergistic effects between bacteriophages and antibiotics enhance bacteriophage lytic activity, reduce antibiotic dosage, significantly lower the risk of resistance development, and demonstrate superior antimicrobial efficacy. This review summarizes the mechanisms and research progress of bacteriophage-antibiotic synergy, aiming to further advance research and clinical application of combined bacteriophage-antibiotic therapy and provide new solutions to address the problem of antibiotic resistance.
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Key words:
- Bacteriophage /
- Antibiotic /
- Combination therapy /
- Resistance /
- Synergistic effects
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图 1 噬菌体-抗生素协同作用机制
注：（1）噬菌体通过作用于细菌外排泵靶点，恢复细菌对抗生素的敏感性；（2）噬菌体编码的多糖去聚合酶等酶类降解生物膜结构，增强抗生素渗透；（3）β-内酰胺类抗生素干扰青霉素结合蛋白，引起细菌丝状化，增强噬菌体的吸附与裂解效率；（4）抗生素通过激活细菌RecA介导的SOS应答，增强细菌裂解和噬菌体增殖。
Figure 1. Synergistic mechanisms of phage–antibiotic therapy
表 1 临床实践中噬菌体-抗生素的联合治疗
Table 1. Phages and antibiotics in clinical practice
Infection Case presentation Phage Antibiotic Clinical outcome Reference 1 Multidrug resistant A. baumannii and K. pneumoniae infection A 42-year-old patient with a trauma-related left tibial infection with drug resistant A. baumannii and K. pneumoniae ϕAbKT21phi3 and ϕKpKT21phi1 Meropenem and colistin Rapid tissue healing and positive culture eradication. The patient’s leg did not have to be amputated and he is undergoing rehabilitation
[35]2 Pandrug-resistant K. pneumoniae A 30-year-old patient with a fracture-associated pandrug-resistant K. pneumoniae infection. phage M1 Meropenem and colistin followed by ceftazidime/avibactam The patient regained the ability to walk and resume activities，with no recurrence of Klebsiella pneumoniae infection.
[36]3 Pseudomonas aeruginosa infection A 75-year-old woman with arteriosclerosis and comorbidities developed Pseudomonas aeruginosa infection after femoropopliteal bypass surgery in the right inguinal area. fNenPA2p2、fNenPA2p4 and fGstaPae02 Meropenem Infection markers normalized. PET-CT showed clinical improvement. No further Pseudomonas aeruginosa septicemia occurred during the 10-month follow-up. [37] 4 Methicillin-Susceptible Staphylococcus Aureus infection A 29-year-old woman with type-1 neurofibromatosis developed an MSSA surgical site infection with a skin fistula one month after ceramic cranioplasty，leading to septic shock and free flap necrosis. two different
bacteriophagesDalbavancin Within two weeks of combination therapy，purulent discharge gradually decreased to no exudate. At 8 months after treatment，the patient remains healthy with no infection recurrence. [38] 5 multidrug resistant Acinetobacter baumannii （MDR-A） respiratory infection A 52-year-old critically ill patient with MDR A. baumannii respiratory infection A.baumannii phage AbW4878Ø1 Tigecycline、Trimethoprim/sulfametoxazole Successfully treated with antibiotics and intravenous and nebulized PT. [39]
6multidrug resistant （MDR） P. aeruginosa pneumonia infection A 26-year-old cystic fibrosis （CF） patient awaiting lung transplantation with multidrug resistant （MDR） P. aeruginosa pneumonia AB-PA01 iprofloxacin、piperacillin–tazobactam and doripenem No worsening or recurrence of pneumonia and cystic fibrosis within 100 days after phage therapy.
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