Omadacycline hydrochloride (PTK0796 hydrochloride) is an aminomethylcycline tetracycline antibiotic[1]. Omadacycline hydrochloride inhibits bacterial protein synthesis by binding the primary tetracycline binding site on the 30S subunit of the bacterial ribosome [2]. Omadacycline hydrochloride overcomes common tetracycline resistance mechanisms and has been widely used to inhibit drug-resistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant and macrolide-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococci (VRE), and Clostridium difficile [3].
In vitro, Omadacycline hydrochloride treatment significantly inhibited the activity of P. falciparum strain 3D7 with an IC50 value of 8.443±0.618µM at 3 days and 0.248±0.109µM at 6 days[4]. Treatment of THP-1-derived macrophages with Omadacycline hydrochloride (100µg/ml) 30 minutes before lipopolysaccharide (LPS) stimulation resulted in a significant decrease in IL-6, CXCL-1, and MMP-9 expression and inhibited IL-8-induced neutrophil chemotaxis[5].
In vivo, Omadacycline hydrochloride treatment via intraperitoneal injection at a dose of 20mg/kg/day for 3 days decreased the parasite load and increased the survival of P. berghei infectious murine model[6]. Omadacycline hydrochloride (5mg/kg) administered intraperitoneally every 12 hours for 6 days inhibited the production of multiple proinflammatory cytokines and reduced neutrophil infiltration in the lungs, improving survival in a mouse model of post-influenza MRSA [7].
References:
[1] Karlowsky J A, Steenbergen J, Zhanel G G. Microbiology and preclinical review of omadacycline[J]. Clinical Infectious Diseases, 2019, 69(Supplement_1): S6-S15.
[2] Zhanel G G, Esquivel J, Zelenitsky S, et al. Omadacycline: a novel oral and intravenous aminomethylcycline antibiotic agent[J]. Drugs, 2020, 80(3): 285.
[3] Burgos R M, Rodvold K A. Omadacycline: a novel aminomethylcycline[J]. Infection and Drug Resistance, 2019: 1895-1915.
[4] de Carvalho L P, Groeger-Otero S, Kreidenweiss A, et al. Boromycin has rapid-onset antibiotic activity against asexual and sexual blood stages of Plasmodium falciparum[J]. Frontiers in Cellular and Infection Microbiology, 2022, 11: 802294.
[5] Sanders M, Beringer P. Immunomodulatory activity of omadacycline in vitro and in a murine model of acute lung injury[J]. mSphere, 2024, 9(11): e00671-24.
[6] Madejczyk M S, Leed S E, Kudyba K, et al. In vitro activity and in vivo efficacy of omadacycline against Plasmodium species[J]. Malaria Journal, 2025, 24(1): 194.
[7] Gomi S, Price E, Burgoyne H, et al. Omadacycline exhibits anti-inflammatory properties and improves survival in a murine model of post-influenza MRSA pneumonia[J]. Antimicrobial Agents and Chemotherapy, 2025, 69(9): e00469-25.
Omadacycline hydrochloride (PTK0796 hydrochloride)是一种氨甲基环素类四环素抗生素[1]。Omadacycline hydrochloride通过结合细菌核糖体30S亚基上的主要四环素结合位点抑制细菌蛋白质合成[2]。Omadacycline hydrochloride能够克服常见的四环素耐药机制，已广泛应用于抑制耐药革兰氏阳性病原体，包括耐甲氧西林金黄色葡萄球菌（MRSA）、耐青霉素和耐大环内酯类肺炎链球菌、耐万古霉素肠球菌（VRE）以及艰难梭菌[3]。
在体外，Omadacycline hydrochloride处理3天和6天可分别抑制恶性疟原虫3D7株活性，IC50值为8.443±0.618µM和0.248±0.109µM[4]。脂多糖（LPS）刺激前30分钟用100µg/ml的Omadacycline hydrochloride预处理THP-1来源的巨噬细胞能显著降低IL-6、CXCL-1和MMP-9表达，并抑制IL-8诱导的中性粒细胞趋化[5]。
在体内，伯氏疟原虫感染小鼠模型每日腹腔注射Omadacycline hydrochloride（20mg/kg/天；持续3天）可降低寄生虫负荷并提高生存率[6]。流感后MRSA肺炎小鼠模型每12小时腹腔注射5mg/kg剂量的Omadacycline hydrochloride（持续6天）能抑制多种促炎细胞因子产生并减少肺部中性粒细胞浸润，提高生存率[7]。