Mannala Gopala K, Rupp Markus, Walter Nike, Youf Raphaelle, Bärtl Susanne, Riool Martijn, Alt Volker
Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany.
Department for Psychosomatic Medicine, University Hospital Regensburg, Regensburg, Germany.
Bone Joint Res. 2024 Aug 2;13(8):383-391. doi: 10.1302/2046-3758.138.BJR-2023-0340.R1.
Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in .
For the haematogenous infection, larvae were implanted with a Kirschner wire (K-wire), infected with , and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses.
In the haematogenous infection, a single combined dose of phages and gentamicin, and repetitive injections with gentamicin or in combination with phages, resulted in significantly improved survival rates. In the early-stage biofilm infection, only repetitive combined administration of phages and gentamicin led to a significantly increased survival. Additionally, a significant reduction in number of bacteria was observed in the larvae after receiving repetitive doses of phages and/or gentamicin in both infection models.
Based on our results, a single dose of the combination of phages and gentamicin is sufficient to prevent a haematogenous implant-related infection, whereas gentamicin needs to be administered daily for the same effect. To treat early-stage implant-related infection, repetitive doses of the combination of phages and gentamicin are required.
噬菌体感染细菌、在细菌内复制,并通过裂解从宿主中释放出来。在此,我们评估重复剂量的噬菌体191219和庆大霉素对血源性和早期生物膜植入相关感染的影响。
对于血源性感染,将克氏针(K线)植入幼虫体内,感染[具体细菌名称未给出],随后给予噬菌体和/或庆大霉素。对于早期生物膜植入感染,K线在植入前用[具体细菌名称未给出]悬液预孵育。24小时后,幼虫接受噬菌体和/或庆大霉素。在两个模型中,幼虫还接受高达五天的每日剂量噬菌体和/或庆大霉素。通过五天的生存分析和重复给药两天后的细菌定量培养来确定效果。
在血源性感染中,噬菌体和庆大霉素的单次联合剂量,以及庆大霉素单独或与噬菌体联合的重复注射,均导致生存率显著提高。在早期生物膜感染中,只有噬菌体和庆大霉素的重复联合给药导致生存率显著提高。此外,在两个感染模型中,幼虫在接受噬菌体和/或庆大霉素的重复剂量后,观察到细菌数量显著减少。
根据我们的结果,噬菌体和庆大霉素的单次联合剂量足以预防血源性植入相关感染,而庆大霉素需要每日给药才能达到相同效果。要治疗早期植入相关感染,需要噬菌体和庆大霉素联合的重复剂量。