In vitro activity of TNP-2092 against periprosthetic joint infection-associated staphylococci

Abstract

Staphylococci are the most common causes of periprosthetic joint infection (PJI). TNP-2092 is an investigational hybrid drug composed of rifamycin and quinolizinone pharmacophores conjugated via a covalent linker. We determined minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum biofilm bactericidal concentration (MBBC) values of TNP-2092 against 80 PJI-associated Staphylococcus aureus and Staphylococcus epidermidis isolates compared to ciprofloxacin and rifampin alone and in combination, alongside daptomycin and vancomycin. TNP-2092 exhibited the following activity against S. aureus: MIC₅₀/MIC_90, ≤0.0075/0.015 μg/mL; MBC₅₀/MBC₉₀, 0.5/4 μg/mL; and MBBC₅₀/MBBC₉₀, 0.5/2 μg/mL, and the following activity against S. epidermidis: MIC₅₀/MIC₉₀, ≤0.0075/0.015 μg/mL; MBC₅₀/MBC₉₀, 0.015/0.125 μg/mL; and MBBC₅₀/MBBC₉₀, 0.06/0.25 μg/mL. TNP-2092 MIC, MBC, and MBBC values were >8 μg/mL for 1 isolate, while MIC values were ≤0.25 μg/mL and MBC and MBBC values were ≤4 μg/mL for all other isolates. Results of this study show that TNP-2092 has promising in vitro activity against PJI-associated staphylococci.

Keywords: Periprosthetic joint infection; Staphylococcus aureus; Staphylococcus epidermidis; TNP-2092.