Reducing Staphylococcus Aureus Burden in Synovial Fluid

Neil Zhao, Thomas Jefferson University


Septic arthritis is a debilitating disease that affects ~20,000 people yearly in the United States. The mortality rate is ~11% and medical expenses can run up to more than $1.6 billion annually. Standard treatment for septic arthritis involves aggressive joint lavage, followed by local and systemic antibiotics, and often necessitates arthrotomy and surgical debridement. Staphylococcus aureus (S. aureus) is the most common causative pathogen of septic arthritis. Infections mediated by S. aureus have a recurrence rate of up to ~45%, which can be attributed to S. aureus forming antibiotic tolerant aggregates in synovial fluid (SynF). Much of the treatment failure and disease recurrence in cases of septic arthritis is attributable to this phenomenon of bacterial aggregation in SynF. Within this thesis, three approaches to reducing S. aureus burden in SynF despite antibiotic tolerance are explored. We elucidated the anti-staphylococcal effect of berberine (BBR), an alkaloid that can be isolated from plants in the Berberidaceae family. We applied ultrasound-targeted microbubble destruction (UTMD) to sensitize S. aureus aggregates to antibiotics. And we explored the development of an aggregate extraction technique using the fibrinogen sol-gel transition to create a fibrin glue. Both BBR and UTMD + antibiotics achieved more than twice the log reduction in S. aureus colony forming units (CFUs) than antibiotics alone. We used the fibrin glue as an alternate method of sterilization, with perhaps more efficacy against bacterial aggregates than antibiotics. All three treatment options also further clarified the phenotype of S. aureus aggregates in terms of metabolic activity, structural composition, and mechanisms of antibiotic tolerance. This thesis will provide an impetus for exploring adjunct treatments for septic arthritis that can be used in conjunction with standard antibiotic therapy to address issues of antibiotic tolerance in SynF.

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Recommended Citation

Zhao, Neil, "Reducing Staphylococcus Aureus Burden in Synovial Fluid" (2022). ETD Collection for Thomas Jefferson University. AAI28966387.