The efficacy and safety of intra-articular dual-acting antibacterial agent (TNP-2092) for implant infection-associated MRSA

Tianyu Dai; Chi Ma; Fan Zhang; Hui Wang; Zhenkun Ma; Huan Wang; Yinxian Wen; Liaobin Chen

doi:10.1093/infdis/jiad588

The efficacy and safety of intra-articular dual-acting antibacterial agent (TNP-2092) for implant infection-associated MRSA

J Infect Dis. 2023 Dec 26:jiad588. doi: 10.1093/infdis/jiad588. Online ahead of print.

Authors

Tianyu Dai¹, Chi Ma^{1

2}, Fan Zhang¹, Hui Wang³, Zhenkun Ma⁴, Huan Wang⁴, Yinxian Wen^{1

5}, Liaobin Chen^{1

5}

Affiliations

¹ Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
² Department of Orthopedics, The First Affiliated Hospital of Jishou University, Jishou, 416000. China.
³ Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China.
⁴ TenNor Therapeutics (Suzhou) Limited 218 Xinghu Street, Building B7 Room 701, Suzhou Industrial Park, Suzhou 215123, China.
⁵ Joint Disease Research Center of Wuhan University, Wuhan University, Wuhan, China.

PMID: 38147364
DOI: 10.1093/infdis/jiad588

Abstract

Owing to the presence of microbial biofilm on the implant, the eradication of biofilm-associated infections poses a challenge for antibiotic therapies. The study aimed to investigate the efficacy and safety of the novel antibiotic agent TNP-2092 in the context of implant infections. In vivo, the periprosthetic joint infection (PJI) rats treated with antibiotics showed an increase in body weight and decrease in swelling, temperature, and width of knee, versus control group. Meanwhile, inflammatory markers in synovium and serum were decreased in TNP-2092 group, consistent with the pathological results. Moreover, TNP-2092 was effective in eliminating bacteria and disruption biofilm formation, and further alleviated the abnormal bone absorption and reactive bone changes around the prosthesis. In conclusion, intra-articular injection of TNP-2092 is effective and safety in treating knee PJI in rat. The study provides a foundation for the future utilization of TNP-2092 in the management of implant-related infections.

Keywords: Implant infection; Methicillin-resistant Staphylococcus aureus; TNP-2092; microbial biofilm.

Plain language summary

Intra-articular application of the novel semi-synthetic antibiotic agent TNP-2092 (rifamycin covalent bond with quinazone) is safe and effective in treating orthopedic implant infection caused by methicillin-resistant S. aureus in a rat model of knee periprosthetic joint infection.