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/MIC90, ≤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.

中文翻译：

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TNP-2092对假体周围关节感染相关葡萄球菌的体外活性。

葡萄球菌是假体周围关节感染（PJI）的最常见原因。TNP-2092是一种研究性混合药物，由利福霉素和喹唑嗪酮药效基团通过共价接头结合而成。我们确定了与80种PJI相关金黄色葡萄球菌和表皮葡萄球菌分离物相比，环丙沙星和利福平单独使用或联合使用时，TNP-2092的最低抑菌浓度（MIC），最低杀菌浓度（MBC）和最低生物膜杀菌浓度（MBBC）值，达托霉素和万古霉素。TNP-2092对金黄色葡萄球菌具有以下活性：MIC50 / MIC90，≤0.0075/ 0.015μg/ mL；MBC50 / MBC90，0.5 / 4μg/ mL; MBBC50 / MBBC90，0.5 / 2μg/ mL，对表皮葡萄球菌具有以下活性：MIC50 / MIC90，≤0.0075/ 0.015μg/ mL；MBC50 / MBC90，0.015 / 0.125μg/ mL; 和MBBC50 / MBBC90，0.06 / 0.25μg/ mL。1个分离株的TNP-2092 MIC，MBC和MBBC值均> 8μg/ mL，而所有其他分离株的MIC值均≤0.25μg/ mL，MBC和MBBC值均≤4μg/ mL。这项研究的结果表明，TNP-2092具有对抗PJI相关葡萄球菌的体外活性。