Although an increased effectiveness has been suggested when phages and antibiotics are combined, this approach has not been tested against a mature biofilm on an endotracheal tube (ETT) surface. This study evaluated the effect of short- and long-term combined phage-antibiotic therapy in a control of a mature biofilm on an ETT surface. Pseudomonas aeruginosa strains, including susceptible and resistant clinical samples, were used to develop the ETT biofilm. Biofilm was treated with 108PFU/mL of phage_2, phage_18 or 5 μg/mL of ceftolozane/tazobactam, alone or in combination with phages. The sequential combination of the two different phages and ceftolozane/tazobactam was also tested. Biofilm viability was assessed after short (2, 4, 24 h) and long-(48, 72 h) term treatment exposure using colony forming unit measurement. For long-term exposition, a new treatment shot was added every 24 h. In the sequential combination, the phage type was switched at 24 h of treatment. Regarding the susceptible strains, the treatments had limited antibiofilm effect after 2, 4 and 24 h. After 48 and 72 h, administering phages alone had no effect on biofilm viability, indicating the emergence of phage-resistant phenotypes. Nonetheless, the combined phage-antibiotic treatment reduced the biofilm viability in about 5-log, whilst antibiotic alone reduced in about 3-log. The sequential combination of phages and antibiotic reduced the biofilm viability in about 6-log. With respect to the resistant strains, no antibiofilm activity was observed regarding the treatment arms. The combination of phages and ceftolozane/tazobactam showed a synergism strain-dependent, being more apparent in susceptible strains.

中文翻译：

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噬菌体与 Ceftolozane/Tazobactam 在铜绿假单胞菌气管插管生物膜中的协同作用。


尽管已表明噬菌体和抗生素联合使用时效果更高，但这种方法尚未针对气管插管 （ETT） 表面的成熟生物膜进行测试。本研究评估了短期和长期联合噬菌体-抗生素治疗对控制 ETT 表面成熟生物膜的效果。铜绿假单胞菌菌株，包括敏感和耐药临床样本，用于形成 ETT 生物膜。用 108PFU/mL 的 phage_2、phage_18 或 5 μg/mL 的头孢洛扎/他唑巴坦单独或与噬菌体联合处理生物膜。还测试了两种不同噬菌体和 ceftolozane/tazobactam 的顺序组合。使用菌落形成单位测量评估短期 （2 、 4 、 24 小时） 和长期 （48、 72 小时） 治疗暴露后的生物膜活力。对于长期暴露，每 24 小时添加一次新的治疗注射。在序贯组合中，噬菌体类型在处理 24 小时时交换。对于易感菌株，处理在 2 、 4 和 24 小时后抗生物膜作用有限。48 小时和 72 小时后，单独施用噬菌体对生物膜活力没有影响，表明出现噬菌体抗性表型。尽管如此，噬菌体-抗生素联合治疗在约 5 个对数中降低了生物膜活力，而单独使用抗生素在约 3 个对数中降低了生物膜活力。噬菌体和抗生素的连续组合降低了约 6 个对数的生物膜活力。对于耐药菌株，在治疗组未观察到抗生物膜活性。噬菌体和头孢洛扎/他唑巴坦的组合显示出协同菌株依赖性，在易感菌株中更为明显。