Racenis Karlis, Rezevska Dace, Madelane Monta, Lavrinovics Ervins, Djebara Sarah, Petersons Aivars, Kroica Juta
Department of Biology and Microbiology, Riga Stradins University, Riga, Latvia.
Center of Nephrology, Pauls Stradins Clinical University Hospital, Riga, Latvia.
Front Med (Lausanne). 2022 Apr 25;9:851310. doi: 10.3389/fmed.2022.851310. eCollection 2022.
High-energy trauma with severe bone fractures can be complicated by infection, leading to the development of osteomyelitis. 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. 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) 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 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 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 assessment of the isolated MDR 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.
伴有严重骨折的高能创伤可能并发感染，导致骨髓炎的发生。由于其高毒力特征以及能够迅速对多种抗菌药物产生耐药性，是此类感染的重要病原体。生物膜会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，噬菌体与某些抗菌药物的联合已显示出协同和相加作用。我们报告一例21岁患者，其在道路交通事故后发生复发性耐多药（MDR）股骨骨髓炎，伴有右股骨近端III B级开放性骨折和严重软组织损伤。尽管进行了广泛的抗菌治疗以及多次伤口清创手术干预，但感染仍持续存在，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及伤口清创、静脉注射（IV）头孢他啶 - 阿维巴坦以及局部应用溶菌性噬菌体鸡尾酒BFC 1.10。干预九个月后，患者未出现任何临床、放射学或实验室炎症迹象；因此，进行了髋关节置换。然而，股骨远端出现复发性感染，并通过传统抗菌药物成功治疗。在本病例中，伤口清创联合抗生素和噬菌体导致股骨近端节段细菌根除，避免了截肢，但未能治疗远端骨节段的骨髓炎。对分离出的耐多药菌株进行了生物膜形成和噬菌体敏感性评估。此外，测定了头孢他啶 - 阿维巴坦和BFC 1.10对浮游细胞生长的抗菌作用，并评估了对细菌生物膜的预防作用。分离出的细菌菌株对噬菌体鸡尾酒敏感。接种后6小时检测到强烈的生物膜形成。头孢他啶 - 阿维巴坦与BFC 1.10联合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，所需的头孢他啶 - 阿维巴坦浓度降低了两倍。本研究证明了噬菌体和抗生素在难以治疗的骨和软组织感染中的可能应用，其中观察到了噬菌体和抗生素的相加作用。
