P-1097. Efficacy of Rifaquizinone in a Murine Model of Prosthetic Joint Infection (PJI) with Fluoroquinolone-Sensitive and -Resistant <i>Staphylococcus aureus</i>

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. Current studies sought to evaluate the therapeutic efficacy of RFQ following intraperitoneal (IP) administration for 7- to14-day treatment in a murine model of S. aureus prosthetic joint infection (PJI). Methods K-wire was implanted in right hindlimb femurs of C57/BL6 mice followed by infection with 6.5-6.9 log10 CFU of a fluoroquinolone-sensitive (UNT005-4) or -resistant (UNT002-3) S. aureus strain. Doses of RFQ, ciprofloxacin, vancomycin, and vehicle were IP administered BID for 7 or 14 consecutive days starting 7 or 21 days after infection. Infected wires and femurs were collected and processed for CFU counts from untreated groups at the start of treatment and treated/vehicle groups within 18 hours of the final administered dose. Results In the 7 day UNT005-4 infection study, mean wire and femur counts for the infection group were 4.77 log10 CFU and 7.89 log10 CFU on Day 7 and for vehicle treatment were 5.02 log10 CFU and 6.83 log10 CFU on Day 14. Comparatively, RFQ at doses of 10, 25, and 62.5 mg/kg for 7 days treatment significantly reduced mean wire and femur counts by &amp;gt; 2.40 and &amp;gt; 1.60 log10 CFU. In the 21 day UNT005-4 infection study, compared to the infection and vehicle treatment, the same doses of RFQ administered for 14 days significantly reduced mean counts by &amp;gt;1.02 log10 CFU for wires and &amp;gt; 0.88 log10 CFU for femurs. In the 21 day UNT002-3 infection study, RFQ administered for 14 days significantly reduced mean counts by &amp;gt; 1.50 log10 CFU for wire and &amp;gt; 0.9 log10 CFU for femur. As expected, reduction in mean counts following 7 or 14 days of ciprofloxacin and vancomycin treatments were less than RFQ. Conclusion RFQ IP administered doses significantly reduced wire- and femur-associated counts for both S. aureus strains, and despite UNT002-3 resistant to ciprofloxacin treatment, the RFQ remained efficacious in the murine PJI model. Disclosures 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 Zhenkun Ma, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee Huan Wang, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee William J Weiss, MS, TenNor Therapeutics (Suzhou) Ltd: Investigator