中文摘要：耐多药(MDR)铜绿假单胞菌感染对人体健康构成严重威胁。噬菌体-抗生素联合治疗有望对抗此类感染。本研究将5噬菌体铜绿假单胞菌混合物-PAM2H，与抗生素(头孢他啶、环丙沙星、庆大霉素、美罗培南) 联合使用，测试PAM2H能否提高抗生素活性。研究发现体外联合治疗显著增加了耐多药菌株对抗生素的敏感性。噬菌体与头孢他啶(CAZ)、美罗培南、庆大霉素或环丙沙星联合治疗，对这些抗生素敏感的铜绿假单胞菌菌株的数量分别增加了63%、56%、31%和81%。此外，在小鼠背伤模型中，用CAZ和PAM2H联合处理3天后，八只小鼠中有七只在受伤4天后伤口没有发现细菌残留；而用CAZ或PAM2H单独处理的所有小鼠，伤口中均有大约10(7)个菌落形成单位(CFU)。治疗后小鼠伤口恢复的铜绿假单胞菌在蜡虫模型中毒性降低，DNA测序表明联合治疗阻止了编码已知噬菌体受体的基因突变。可见，PAM2H联合抗生素治疗实现了铜绿假单胞菌在体外对抗生素的再敏化，并协同减少体内的细菌负担。
外文摘要：Multidrug-resistant (MDR) Pseudomonas aeruginosa infections pose a serious health threat. Bacteriophage-antibiotic combination therapy is a promising candidate for combating these infections. A 5-phage P. aeruginosa cocktail, PAM2H, was tested in combination with antibiotics (ceftazidime, ciprofloxacin, gentamicin, meropenem) to determine if PAM2H enhances antibiotic activity. Combination treatment in vitro resulted in a significant increase in susceptibility of MDR strains to antibiotics. Treatment with ceftazidime (CAZ), meropenem, gentamicin, or ciprofloxacin in the presence of the phage increased the number of P. aeruginosa strains susceptible to these antibiotics by 63%, 56%, 31%, and 81%, respectively. Additionally, in a mouse dorsal wound model, seven of eight mice treated with a combination of CAZ and PAM2H for three days had no detectable bacteria remaining in their wounds on day 4, while all mice treated with CAZ or PAM2H alone had similar to 10(7) colony forming units (CFU) remaining in their wounds. P. aeruginosa recovered from mouse wounds post-treatment showed decreased virulence in a wax worm model, and DNA sequencing indicated that the combination treatment prevented mutations in genes encoding known phage receptors. Treatment with PAM2H in combination with antibiotics resulted in the re-sensitization of P. aeruginosa to antibiotics in vitro and a synergistic reduction in bacterial burden in vivo.
外文关键词：Pseudomonas aeruginosa；phage therapy；phage-antibiotic synergy； antimicrobial resistance；re-sensitization
作者：Engeman, E；Freyberger, HR；Corey, BW；Ward, AM；He, YX；Nikolich, MP；Filippov, AA；Tyner, SD；Jacobs, AC
作者单位：Walter Reed Army Inst Res；Oak Ridge Inst Sci & Educ ORISE；ICON Plc
期刊名称：PHARMACEUTICALS
期刊影响因子：4.286
出版年份：2021
出版刊次：3
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