Clinical Application of Customized and Non-customized Bacteriophage Therapy in Patients with Refractory/Resistant Bacterial Infections: A Systematic Review and Meta-analysis.
Yang Liu, Shuhua Thong, Wilfried Moreira, Jia Hao Yeo, Yang Zhong, Zhi-Soon Chong, Tse Hua Nicholas Wong, Shimin Jasmine Chung, Andrea Lay Hoon Kwa
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引用次数: 0
Abstract
Background: Patients with refractory/resistant bacterial infection face high mortality rates. Bacteriophage therapy (PT) is a viable solution, but clinical evidence remains fragmented. This review synthesizes current evidence on PT efficacy, safety, and implementation, with additional analysis by customization strategies: non-customized, customized selection, and customized production.
Method: We examined clinical studies on PTs for refractory/resistant bacterial infections and pooled efficacy and safety outcomes by customization strategy from randomized controlled trials, observational studies, cohorts, case series, and case reports using a random-effects model. Subset sensitivity analyses were conducted, and individual patient data were further analyzed. Risk of bias was assessed for each study.
Result: As of May 14, 2025, 16226 articles were identified, and 130 studies (1115 patients) were included: 559 non-customized, 451 customized selection, and 105 customized production. Risks of bias were low to serious. Clinical improvement (I2 88%) and bacterial eradication (I2 94%) rates were 72% (95% confidence interval [CI], 61-81) and 51% (95%CI, 30-72), respectively. Customized production group had the highest success rates (79% and 87%), albeit at a cost. Time taken for customization often resulted in delays in PT. Higher titers and multiple administration routes were associated with better bacterial eradication. Efficacy improvement compared to control was statistically insignificant. Adverse events were mild-to-moderate. Phage neutralization appeared before, during, and after PT cessation. Impacts on pharmacokinetics remain uncertain. Immunological markers varied across studies.
Conclusions: PT shows promising clinical outcomes, but significant gaps in clinical evidence persist, warranting well-designed trials. Laboratory-based phage monitoring shows promise but requires systematic investigation.
期刊介绍：
The International Journal of Antimicrobial Agents is a peer-reviewed publication offering comprehensive and current reference information on the physical, pharmacological, in vitro, and clinical properties of individual antimicrobial agents, covering antiviral, antiparasitic, antibacterial, and antifungal agents. The journal not only communicates new trends and developments through authoritative review articles but also addresses the critical issue of antimicrobial resistance, both in hospital and community settings. Published content includes solicited reviews by leading experts and high-quality original research papers in the specified fields.
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