PDF(Pubmed)
Abstract：
High-energy trauma with severe bone fractures can be complicated by infection, leading to the development of osteomyelitis. Pseudomonas aeruginosa is an important causative agent of such infections because of its high virulence profile and ability to develop resistance against a wide range of antimicrobials quickly. P. aeruginosa biofilms cause treatment failure and relapsing infections. Bacteriophages are viruses that can be used to treat biofilm-associated infections. Moreover, the combination of phages with certain antimicrobials have demonstrated synergistic and additive effects. We present a case of a 21-year-old patient with relapsing multidrug-resistant (MDR) P. aeruginosa femur osteomyelitis that developed after a road accident, with a proximal right femoral Grade III B open fracture and severe soft tissue damage. Despite extensive antimicrobial treatment and multiple surgical interventions with wound debridement, the infection persisted, with subsequent development of femoral osteomyelitis with a fistula. Patient care management included femoral head excision with wound debridement, intravenous (IV) ceftazidime-avibactam, and the local application of the lytic Pseudomonas bacteriophage cocktail BFC 1.10. Nine months after the intervention, the patient did not show any clinical, radiological, or laboratory signs of inflammation; therefore, hip replacement was performed. Nevertheless, recurrent P. aeruginosa infection evolved at the distal side of the femur and was successfully treated with conventional antimicrobials. In this case, wound debridement combined with antibiotics and bacteriophages resulted in bacterial eradication of proximal femoral segment, avoiding leg amputation, but failed to treat osteomyelitis in distal bone segment. An in vitro assessment of the isolated MDR P. aeruginosa strain for biofilm formation and phage susceptibility was performed. Additionally, the antimicrobial effects of ceftazidime-avibactam and BFC 1.10 were determined on planktonic cell growth and bacterial biofilm prevention was evaluated. The isolated bacterial strains were susceptible to the bacteriophage cocktail. Strong biofilm formation was detected 6 h after inoculation. Ceftazidime-avibactam combined with BFC 1.10 was most effective in preventing planktonic cell growth and biofilm formation. In both cases, the required concentration of ceftazidime-avibactam decreased two-fold. This study demonstrates the possible use of bacteriophages and antibiotics in difficult-to-treat bone and soft tissue infections, where the additive effects of phages and antibiotics were observed.
摘要：
高能量创伤伴严重骨折可并发感染，导致骨髓炎的发展。铜绿假单胞菌是此类感染的重要致病因子,因为其具有高毒力特性和快速产生对多种抗微生物剂的抗性的能力。铜绿假单胞菌生物膜导致治疗失败和复发性感染。噬菌体是可用于治疗生物膜相关感染的病毒。此外，噬菌体与某些抗微生物剂的组合已显示出协同和累加效应。我们介绍了一名21岁的复发性多药耐药（MDR）铜绿假单胞菌股骨骨髓炎患者，该患者在道路交通事故后发展。右股骨近端IIIB级开放性骨折和严重的软组织损伤。尽管广泛的抗菌治疗和伤口清创的多种手术干预，感染持续存在，随后发展为伴有瘘管的股骨骨髓炎。患者护理管理包括股骨头切除和伤口清创术，静脉注射(IV)头孢他啶-阿维巴坦，和裂解假单胞菌噬菌体鸡尾酒BFC的局部应用1.10。干预后九个月，病人没有表现出任何临床，放射学,或炎症的实验室迹象；因此，进行了髋关节置换.然而，复发性铜绿假单胞菌感染在股骨远端发展，并成功使用常规抗菌药物治疗。在这种情况下,伤口清创术联合抗生素和噬菌体导致股骨近端细菌根除，避免截肢,但未能治疗远端骨段骨髓炎。对分离的MDR铜绿假单胞菌菌株的生物膜形成和噬菌体敏感性进行体外评估。此外,测定了头孢他啶-阿维巴坦和BFC1.10对浮游细胞生长的抗菌作用,并评估了细菌生物膜的预防作用.分离的细菌菌株对噬菌体混合物敏感。接种后6小时检测到强烈的生物膜形成。头孢他啶-阿维巴坦联合BFC1.10在预防浮游细胞生长和生物膜形成方面最有效。在这两种情况下，头孢他啶-阿维巴坦的所需浓度降低了2倍。这项研究表明，噬菌体和抗生素可能用于难以治疗的骨骼和软组织感染，观察到噬菌体和抗生素的加性效应。
