University of Florida, Orlando, Florida, USA.
Paratek Pharmaceuticals, Inc., King of Prussia, Pennsylvania, USA.
Antimicrob Agents Chemother. 2024 Sep 4;68(9):e0059524. doi: 10.1128/aac.00595-24. Epub 2024 Aug 12.
, the causative agent of anthrax, is among the most likely bacterial pathogens to be used in a biological attack. Inhalation anthrax is a serious, life-threatening form of infection, and the mortality from acute inhaled anthrax can approach 100% if not treated early and aggressively. Food and Drug Administration-approved antibiotics indicated for post-exposure prophylaxis (PEP) or treatment of anthrax are limited. This study assessed the activity and efficacy of omadacycline and comparators against clinical isolates of including a ciprofloxacin-resistant isolate. Minimum inhibitory concentrations (MICs) of omadacycline, ciprofloxacin, and doxycycline were determined against animal and human clinical isolates of , including the ciprofloxacin-resistant Ames strain BAC4-2. Mice were challenged with aerosolized BAC4-2 spores, and survival was monitored for 28 days post-challenge. Treatment was initiated 24 h after aerosol challenge and administered for 14 days. Omadacycline demonstrated activity against 53 isolates with an MIC range of ≤0.008-0.25 µg/mL, and an MIC/MIC of 0.015/0.03 µg/mL. Consistent with this, omadacycline demonstrated efficacy in a PEP mouse model of inhalation anthrax caused by the Ames BAC4-2 ciprofloxacin-resistant isolate. Omadacycline treatment significantly increased survival compared with the vehicle control group and the ciprofloxacin treatment group. As antibiotic resistance rates continue to rise worldwide, omadacycline may offer an alternative PEP or treatment option against inhalation anthrax, including anthrax caused by antibiotic-resistant .
炭疽杆菌是炭疽病的病原体，是最有可能被用于生物攻击的细菌病原体之一。吸入性炭疽是一种严重的、危及生命的感染形式，如果不早期积极治疗，急性吸入性炭疽的死亡率接近 100%。美国食品和药物管理局批准的用于接触后预防（PEP）或炭疽治疗的抗生素有限。本研究评估了奥马环素和对照药物对包括耐环丙沙星分离株在内的临床分离炭疽杆菌的活性和疗效。测定了奥马环素、环丙沙星和强力霉素对动物和人类临床分离炭疽杆菌，包括耐环丙沙星的艾姆斯株 BAC4-2 的最低抑菌浓度（MIC）。用气溶胶化 BAC4-2 孢子对小鼠进行攻击，在攻击后 28 天监测存活情况。在气溶胶攻击后 24 小时开始治疗，并持续 14 天。奥马环素对 53 株分离株具有活性，MIC 范围为≤0.008-0.25 µg/mL，MIC/MIC 为 0.015/0.03 µg/mL。奥马环素在由艾姆斯 BAC4-2 耐环丙沙星分离株引起的吸入性炭疽 PEP 小鼠模型中也显示出疗效。奥马环素治疗组与载体对照组和环丙沙星治疗组相比，显著提高了存活率。随着全球抗生素耐药率的不断上升，奥马环素可能为吸入性炭疽，包括抗生素耐药炭疽杆菌引起的炭疽提供一种替代 PEP 或治疗选择。
