微生物学
抗生素
噬菌体疗法
铜绿假单胞菌
噬菌体
生物膜
抗生素耐药性
美罗培南
化学
抗菌剂
细菌
生物
大肠杆菌
生物化学
遗传学
基因
作者
Baixing Chen,Luis Ponce Benavente,Marco Chittò,Jacek K. Wychowaniec,Virginia Post,Matteo D’Este,Caroline Constant,Stephan Zeiter,Wenli Feng,Mercedes González Moreno,Andrej Trampuž,Jeroen Wagemans,Jolien Onsea,R. Geoff Richards,Rob Lavigne,T. Fintan Moriarty,Willem‐Jan Metsemakers
标识
DOI:10.1016/j.jconrel.2023.10.029
摘要
Bacteriophage (phage) therapy has shown promise in treating fracture-related infection (FRI); however, questions remain regarding phage efficacy against biofilms, phage-antibiotic interaction, administration routes and dosing, and the development of phage resistance. The goal of this study was to develop a dual antibiotic-phage delivery system containing hydrogel and alginate microbeads loaded with a phage cocktail plus meropenem and evaluate efficacy against muti-drug resistant Pseudomonas aeruginosa. Two phages (FJK.R9–30 and MK.R3–15) displayed enhanced antibiotic activity against P. aeruginosa biofilms when tested in combination with meropenem. The antimicrobial activity of both antibiotic and phage was retained for eight days at 37 °C in dual phage and antibiotic loaded hydrogel with microbeads (PA-HM). In a mouse FRI model, phages were recovered from all tissues within all treatment groups receiving dual PA-HM. Moreover, animals that received the dual PA-HM either with or without systemic antibiotics had less incidence of phage resistance and less serum neutralization compared to phages in saline. The dual PA-HM could reduce bacterial load in soft tissue when combined with systemic antibiotics, although the infection was not eradicated. The use of alginate microbeads and injectable hydrogel for controlled release of phages and antibiotics, leads to the reduced development of phage resistance and lower exposure to the adaptive immune system, which highlights the translational potential of the dual PA-HM. However, further optimization of phage therapy and its delivery system is necessary to achieve higher bacterial killing activity in vivo in the future.
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