Jahanbakhsh S, Howland J, Ndayishimiye Uwineza M O, Thwaites M T, Pillar C M, Serio A W, Anastasiou D M, Hufnagel D A
Microbiologics Antibiotic and Microbiome Research Center, Kalamazoo, MI, USA.
Paratek Pharmaceuticals, Inc., King of Prussia, PA, USA.
JAC Antimicrob Resist. 2023 Sep 15;5(5):dlad104. doi: 10.1093/jacamr/dlad104. eCollection 2023 Oct.
Omadacycline is an aminomethylcycline antibiotic in the tetracycline class that was approved by the US FDA in 2018 for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. It is available in both IV and oral formulations. Omadacycline has broad-spectrum activity and clinical efficacy against infections caused by Gram-positive and Gram-negative pathogens. Omadacycline is being evaluated in a 3 month placebo-controlled Phase 2 clinical trial of oral omadacycline versus placebo in adults with non-tuberculous mycobacteria (NTM) pulmonary disease caused by (NCT04922554).
To determine if omadacycline has intracellular antimicrobial activity against NTM, bacteria that can cause chronic lung disease, in an model of intracellular infection.
Two strains of were used to infect THP-1 macrophages. Intracellular was then challenged with omadacycline and control antibiotics at multiples of the MIC over time to evaluate intracellular killing.
At 16 × the MIC at 72 h, omadacycline treatment of intracellular NTM yielded a log reduction in cfu of 1.1 (91.74% reduction in cfu) and 1.6 (97.65% reduction in cfu) consistent with killing observed with tigecycline, whereas amikacin and clarithromycin at 16 × the MIC did not show any reduction in cfu against the intracellular .
Omadacycline displayed intracellular activity against within macrophages. The activity was similar to that of tigecycline; as expected, intracellular killing was not observed with clarithromycin and amikacin.
奥马环素是一种四环素类氨甲基环素抗生素，于2018年获美国食品药品监督管理局批准用于治疗社区获得性细菌性肺炎以及急性细菌性皮肤和皮肤结构感染。它有静脉注射和口服两种剂型。奥马环素对革兰氏阳性和革兰氏阴性病原体引起的感染具有广谱活性和临床疗效。目前正在进行一项为期3个月的安慰剂对照2期临床试验，比较口服奥马环素与安慰剂对由非结核分枝杆菌（NTM）引起的非结核分枝杆菌肺病成人患者的疗效（NCT04922554）。
在细胞内感染模型中，确定奥马环素对可导致慢性肺病的NTM是否具有细胞内抗菌活性。
使用两株NTM感染THP-1巨噬细胞。然后用奥马环素和对照抗生素以高于最低抑菌浓度（MIC）的倍数对细胞内NTM进行不同时间的攻击，以评估细胞内杀菌情况。
在72小时时，当药物浓度为MIC的16倍时，奥马环素治疗细胞内NTM使菌落形成单位（cfu）对数减少1.1（cfu减少91.74%）和1.6（cfu减少97.65%），这与替加环素观察到的杀菌效果一致，而当药物浓度为MIC的16倍时，阿米卡星和克拉霉素对细胞内NTM的cfu没有显示出任何减少。
奥马环素在巨噬细胞内对NTM显示出细胞内活性。该活性与替加环素相似；正如预期的那样，克拉霉素和阿米卡星未观察到细胞内杀菌作用。
