P-1111. Efficacy of Intra-Articular Administration of Rifaquizinone in Rodent Models of Implant Infection Associated with Staphylococcus aureus
Authors: Weiss William J , Pulse Mark E , Nguyen Phung , Valtierra David , Peterson Kelly , Ogbonna Adaeze , Beeman Lane , Dai Tianyu , Chen Liaobin , Wang Huan , Ma Zhenkun 
Published: January 2025

Abstract

Background
Rifaquizinone (RFQ, TNP-2092) is a novel multitargeting drug conjugate in development for the treatment of serious or life-threatening bacterial infections including those caused by gram-positive pathogens that have developed or acquired resistance to commonly used antibiotics and those associated with medical devices. RFQ exerts its antibacterial activity by inhibiting RNA polymerase, DNA gyrase, and topoisomerase IV. The current studies were conducted to evaluate the therapeutic efficacy of RFQ following intra-articular (IA) administration in two rodent prosthetic joint infections models with S. aureus.

Methods
Female C57BL/6 mice and male Wistar rats were used. Following surgical insertion of a metal wire into the femoral canal, the surgical site was inoculated with approximately 7 log10 CFU of an S. aureus strain. RFQ and control drugs were IA administered into mice and rats starting 7 days post-surgery once daily for 7 and 14 days, respectively. At 24 hours after the last dose, the wire and femur were aseptically removed and processed for bacterial titers.

Results
In the mice, mean wire and femur counts for the untreated controls at the end of the study were 4.77 and 6.88 log10 CFU, respectively. IA delivered RFQ resulted in mean wire and femur counts that were 2.50-2.72 log10 CFU and 1.71-3.42 log10 CFU lower than the untreated controls, respectively (p ≤ 0.0001). In the rats, mean wire and femur counts for the untreated controls at the end of the study were 6.02 and 5.06 log10 CFU, respectively. RFQ resulted in mean wire and femur counts that were 3.32-5.02 log10 CFU and 1.21-1.96 log10 CFU lower than the untreated controls, respectively (p ≤ 0.01). RFQ administration in the rats resulted in reduced knee swelling and expression of systemic inflammatory markers, a decrease in signs of femoral osteomyelitis and decreased biofilm formation. Doses of RFQ in both species were statistically more effective than vancomycin in reducing the bacterial burden.

Conclusion
The results of these studies indicate that IA injection of RFQ is effective in treating infections related to orthopedic implants. The studies serve as a basis for the use of RFQ in orthopedic practice and the treatment of serious implant-associated infections.

Disclosures
William J Weiss, MS, TenNor Therapeutics (Suzhou) Ltd: Investigator Mark E Pulse, MS, TenNor Therapeutics (Suzhou) Ltd: Investigator Phung Nguyen, BS, TenNor Therapeutics (Suzhou) Ltd: Investigator David Valtierra, Master, TenNor Therapeutics (Suzhou) Ltd: Investigator Kelly Peterson, PhD, TenNor Therapeutics (Suzhou) Ltd: Investigator Adaeze Ogbonna, Bachelor, TenNor Therapeutics (Suzhou) Ltd: Investigator Lane Beeman, Bachelor, TenNor Therapeutics (Suzhou) Ltd: Investigator Tianyu Dai, PhD, TenNor Therapeutics (Suzhou) Ltd: Investigator Liaobin Chen, PhD, TenNor Therapeutics (Suzhou) Ltd: Investigator Huan Wang, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee Zhenkun Ma, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee