Clinical Laboratory Center, First Affiliated Hospital of Jinan University, Guangzhou, China.
The Kjellerup Biofilm Laboratory, Department of Civil and Environmental Engineering, University of Maryland, College Park, Maryland, USA.
J Orthop Res. 2024 Feb;42(2):484-490. doi: 10.1002/jor.25692. Epub 2023 Oct 2.
Bacteriophage therapy is a promising adjuvant therapy for the treatment of periprosthetic joint infections. However, there is a paucity of knowledge about the activity of bacteriophages in synovial fluid. Therefore, this study evaluated the activity of a clinically used bacteriophage in synovial fluid as well as the ability of that bacteriophage to prevent the formation of and eradicate bacteria in synovial fluid induced aggregates. The results of this study reinforce that synovial fluid induced aggregates form rapidly in numerous synovial fluid concentrations. More importantly, there was a statistically significant reduction in bacteriophage activity in synovial fluid compared to tryptic soy broth (p < 0.05) and the bacteriophage could not prevent the formation synovial fluid induced aggregates. Also the bacteriophage could not significantly reduce the amount of bacteria in the synovial fluid induced aggregates when compared to controls, and this was not secondary to resistance. Rather the reduced activity seems to be caused by bacteriophages being hindered in the ability to attach to bacterial receptors. We hypothesize this occurred because the viscosity of synovial fluid slowed bacteriophage interactions with planktonic bacteria and the synovial fluid polymers obstructed the bacteriophage attachment receptors thereby preventing attachment to bacteria in the aggregates. These findings have clinical ramifications, supporting the use of bacteriophage therapy as an adjunct to surgical interventions and not in isolation, at the nascent stage. While these findings show a shortcoming of bacteriophage therapy in periprosthetic joint infections, the knowledge gained should spearhead further research to ultimately devise effective and reproducible bacteriophage therapeutics.
噬菌体疗法是治疗人工关节假体周围感染的一种很有前途的辅助治疗方法。然而，关于噬菌体在滑液中的活性知之甚少。因此，本研究评估了一种临床应用的噬菌体在滑液中的活性，以及该噬菌体预防和清除滑液诱导聚集物中细菌的能力。本研究的结果证实，在许多滑液浓度下，滑液诱导的聚集物迅速形成。更重要的是，与胰蛋白酶大豆肉汤相比，噬菌体在滑液中的活性有显著降低（p<0.05），并且噬菌体不能预防滑液诱导聚集物的形成。此外，与对照组相比，噬菌体不能显著减少滑液诱导聚集物中的细菌数量，这并不是由于耐药性所致。相反，噬菌体活性的降低似乎是由于噬菌体在附着到细菌受体的能力上受到阻碍。我们假设这是因为滑液的粘性减缓了噬菌体与浮游细菌的相互作用，并且滑液聚合物阻碍了噬菌体附着受体，从而阻止了噬菌体在聚集物中附着到细菌上。这些发现具有临床意义，支持在早期将噬菌体疗法作为手术干预的辅助手段而不是单独使用。虽然这些发现显示了噬菌体疗法在人工关节假体周围感染中的局限性，但获得的知识应该引领进一步的研究，最终设计出有效和可重复的噬菌体治疗方法。
