Weiss Shay, Altboum Zeev, Glinert Itai, Schlomovitz Josef, Sittner Assa, Bar-David Elad, Kobiler David, Levy Haim
Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel.
Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona, Israel
Antimicrob Agents Chemother. 2015 Dec;59(12):7497-503. doi: 10.1128/AAC.01376-15. Epub 2015 Sep 21.
Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10(5) CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone.
在没有早期使用抗生素治疗的情况下,呼吸道炭疽是一种致命疾病。兔子通过鼻内滴注对炭疽芽孢杆菌孢子高度易感,在感染后2至4天内死亡。本研究旨在测试抗生素疗法在这种相关动物模型中治疗全身性炭疽的效果。将抗生素给药的起始时间推迟到感染后超过24小时,会导致动物出现不同程度菌血症和毒血症的全身性炭疽。据报道,人类症状在接触后第1至7天开始出现,将治疗起始时间推迟24至48小时(抗生素大规模分发的时间范围)可能会导致患病群体。我们评估了抗生素给药的疗效与治疗开始时菌血症水平的关系。在此,我们将克拉霉素、阿莫西林 - 克拉维酸(奥格门汀)、亚胺培南、万古霉素、利福平及利奈唑胺的治疗效果与先前报道的强力霉素和环丙沙星的疗效进行比较。我们证明,阿莫西林 - 克拉维酸、亚胺培南、万古霉素和利奈唑胺的治疗效果与强力霉素和环丙沙星相同,可治愈菌血症水平高达10(5) CFU/ml的兔子。克拉霉素和利福平仅显示作为暴露后预防性治疗有效,但未能治疗炭疽的全身性(菌血症)阶段。此外,我们评估了克林霉素和环丙沙星联合治疗的作用,结果表明与单独使用环丙沙星相比,联合治疗的疗效有所提高。