PDF(Pubmed)
Abstract：
Inhalation anthrax is the most severe form of Bacillus anthracis infection, often progressing to fatal conditions if left untreated. While recommended antibiotics can effectively treat anthrax when promptly administered, strains engineered for antibiotic resistance could render these drugs ineffective. Telavancin, a semisynthetic lipoglycopeptide antibiotic, was evaluated in this study as a novel therapeutic against anthrax disease. Specifically, the aims were to (i) assess in vitro potency of telavancin against 17 B. anthracis isolates by minimum inhibitory concentration (MIC) testing and (ii) evaluate protective efficacy in rabbits infected with a lethal dose of aerosolized anthrax spores and treated with human-equivalent intravenous telavancin doses (30 mg/kg every 12 hours) for 5 days post-antigen detection versus a humanized dose of levofloxacin and vehicle control. Blood samples were collected at various times post-infection to assess the level of bacteremia and antibody production, and tissues were collected to determine bacterial load. The animals\' body temperatures were also recorded. Telavancin demonstrated potent bactericidal activity against all strains tested (MICs 0.06-0.125 μg/mL). Further, telavancin conveyed 100% survival in this model and cleared B. anthracis from the bloodstream and organ tissues more effectively than a humanized dose of levofloxacin. Collectively, the low MICs against all strains tested and rapid bactericidal in vivo activity demonstrate that telavancin has the potential to be an effective alternative for the treatment or prophylaxis of anthrax infection.
摘要：
吸入性炭疽是最严重的炭疽杆菌感染形式，如果不及时治疗，通常会发展到致命的状况。虽然推荐的抗生素在及时服用时可以有效治疗炭疽，针对抗生素耐药性设计的菌株可能使这些药物无效。Telavancin,一种半合成脂糖肽抗生素，在这项研究中被评估为一种新型的治疗炭疽病的方法。具体来说,其目的是(i)通过最低抑菌浓度(MIC)试验评估泰拉万星对17种炭疽杆菌分离株的体外效力;(ii)与人源化剂量的左氧氟沙星和溶媒对照相比,评估感染致死剂量的雾化炭疽孢子并在抗原检测后用相当于人静脉内泰拉万星剂量(每12小时30mg/kg)治疗5天的兔的保护效力.在感染后的不同时间收集血样，以评估菌血症和抗体产生的水平，并收集组织以确定细菌载量。还记录了动物的体温。Telavancin对所有测试的菌株都表现出有效的杀菌活性（MIC为0.06-0.125μg/mL）。Further,telavancin在该模型中提供了100％的存活率，并且比人源化剂量的左氧氟沙星更有效地从血液和器官组织中清除了炭疽杆菌。总的来说，对所有测试菌株的低MIC和快速的体内杀菌活性表明，telavancin有可能成为治疗或预防炭疽感染的有效替代品。
