Ultrasound combined with voriconazole for treating acute fungal periprosthetic joint infection caused by Candida albicans

Aims

Currently, fungal periprosthetic joint infection (FPJI) following joint arthroplasty remains a major therapeutic challenge worldwide. Therefore, this study aims to investigate a novel and promising therapeutic approach.

Methods

In the in vitro experiment, ultrasound and voriconazole (VOR) were used alone or in combination against Candida albicans . In the in vivo experiment, 100 male Sprague-Dawley rats were randomly divided into ten groups, with ten rats in each group: control group (underwent sham surgery), prosthesis group (uninfected prosthesis implanted), model group (prosthesis implanted and infected with C. albicans ); the remaining seven groups were treated using separate therapeutic methods for infections: ultrasound, intra-articular (IA) (IA VOR injection), IA + ultrasound, intravenous (IV) (IV VOR injection), IV + ultrasound, IA + IV, and IA + IV + ultrasound groups. Relevant tests and examinations were performed during and after the 14-day treatment.

Results

In vitro, the combination of ultrasound and VOR showed the most pronounced antifungal effect. In vivo, IA VOR injection is better for maintaining high local VOR concentrations. Based on this, the combination of ultrasound and IA VOR demonstrated superior outcomes across multiple endpoints, including serum biochemical markers, weightbearing scores, reactive bone changes, inflammation, and local knee skin temperature, as well as reduced colony counts on soft tissues, bone, and implants. In contrast, IV VOR showed minimal improvement across these parameters. Moreover, in rats subjected to any VOR and ultrasound treatment, no pathological changes in major metabolic organs or abnormal serum markers were observed. Additionally, no skin pathological changes were found after ultrasound exposure.

Conclusion

The combination of ultrasound and IA injection of VOR represents a novel and promising therapeutic strategy for C. albicans -induced FPJI.

Cite this article: Bone Joint Res  2026;15(7):752–766.