Adjunct phage treatment enhances the effectiveness of low antibiotic concentration against Staphylococcus aureus biofilms in vitro

Phage therapy is drawing more interest as antibiotic resistance becomes an ever more serious threat to public health. Bacterial biofilms represent a major obstacle in the fight against bacterial infections as they are inherently refractory to many types of antibiotics. Treating biofilms with phage has shown promise in a handful of experimental and case studies. However, quantification of the effect of phage combined with antibiotics is needed to pave the way for larger clinical trials. Here we explore the effect of using phage in combination with a total of nine antibiotics, applied simultaneously or as a pretreatment before antibiotics are applied to in vitro biofilms of Staphylococcus aureus. Most antibiotics alone were ineffective at low concentration (2xMIC), but the addition of phage to treatment regimens led to substantial improvements in efficacy. At high concentration (10xMIC), antibiotics alone were effective, and in most cases the addition of phage to treatment regimens did not improve efficacy. Using phage with rifampin was also very effective at reducing the outgrowth of resistant strains during the course of treatment.

随着抗生素耐药性对公共卫生构成日益严重的威胁，噬菌体疗法正受到越来越多的关注。细菌生物被膜是抗击细菌感染的主要障碍，因为它们本身对多种类型的抗生素具有耐药性。在一些实验和案例研究中，用噬菌体治疗生物被膜已显示出前景。然而，需要对噬菌体与抗生素联合使用的效果进行量化，以便为更大规模的临床试验铺平道路。在此，我们研究了将噬菌体与总共九种抗生素联合使用的效果，这些抗生素同时使用，或者在应用于金黄色葡萄球菌体外生物被膜之前作为预处理使用。大多数抗生素在低浓度（2倍最小抑菌浓度）下单独使用是无效的，但在治疗方案中添加噬菌体可显著提高疗效。在高浓度（10倍最小抑菌浓度）下，抗生素单独使用是有效的，并且在大多数情况下，在治疗方案中添加噬菌体并不能提高疗效。在治疗过程中，将噬菌体与利福平一起使用在减少耐药菌株的增殖方面也非常有效。