Institute for Therapeutic Innovation, University of Florida, Orlando, Florida, USA
Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Antimicrob Agents Chemother. 2017 Aug 24;61(9). doi: 10.1128/AAC.00788-17. Print 2017 Sep.
is considered a likely agent to be used as a bioweapon, and the use of a strain resistant to the first-line antimicrobial treatments is a concern. We determined treatment efficacies against a ciprofloxacin-resistant strain of (Cip Ames) in a murine inhalational anthrax model. Ten groups of 46 BALB/c mice were exposed by inhalation to 7 to 35 times the 50% lethal dose (LD) of Cip Ames spores. Commencing at 36 h postexposure, groups were administered intraperitoneal doses of sterile water for injections (SWI) and ciprofloxacin alone (control groups), or ciprofloxacin combined with two antimicrobials, including meropenem-linezolid, meropenem-clindamycin, meropenem-rifampin, meropenem-doxycycline, penicillin-linezolid, penicillin-doxycycline, rifampin-linezolid, and rifampin-clindamycin, at appropriate dosing intervals (6 or 12 h) for the respective antibiotics. Ten mice per group were treated for 14 days and observed until day 28. The remaining animals were euthanized every 6 to 12 h, and blood, lungs, and spleens were collected for lethal factor (LF) and/or bacterial load determinations. All combination groups showed significant survival over the SWI and ciprofloxacin controls: meropenem-linezolid ( = 0.004), meropenem-clindamycin ( = 0.005), meropenem-rifampin ( = 0.012), meropenem-doxycycline ( = 0.032), penicillin-doxycycline ( = 0.012), penicillin-linezolid ( = 0.026), rifampin-linezolid ( = 0.001), and rifampin-clindamycin ( = 0.032). In controls, blood, lung, and spleen bacterial counts increased to terminal endpoints. In combination treatment groups, blood and spleen bacterial counts showed low/no colonies after 24-h treatments. The LF fell below the detection limits for all combination groups yet remained elevated in control groups. Combinations with linezolid had the greatest inhibitory effect on mean LF levels.
被认为是一种可能被用作生物武器的病原体，而使用对一线抗菌治疗具有耐药性的菌株是一个令人担忧的问题。我们在吸入性炭疽的小鼠模型中确定了针对环丙沙星耐药菌株（Cip Ames）的治疗效果。将 10 组 46 只 BALB/c 小鼠通过吸入暴露于 7 至 35 倍的环丙沙星耐药菌株（Cip Ames 孢子）的 50%致死剂量（LD）。从暴露后 36 小时开始，将各组腹腔内给予无菌注射用水（SWI）和环丙沙星单独治疗（对照组），或环丙沙星联合两种抗菌药物，包括美罗培南-利奈唑胺、美罗培南-克林霉素、美罗培南-利福平、美罗培南-多西环素、青霉素-利奈唑胺、青霉素-多西环素、利福平-利奈唑胺和利福平-克林霉素，在相应抗生素的适当剂量间隔（6 或 12 小时）进行给药。每组 10 只小鼠治疗 14 天并观察至第 28 天。其余动物每 6 至 12 小时安乐死一次，并收集血液、肺和脾脏进行致死因子（LF）和/或细菌载量测定。所有联合组的存活率均显著高于 SWI 和环丙沙星对照组：美罗培南-利奈唑胺（=0.004）、美罗培南-克林霉素（=0.005）、美罗培南-利福平（=0.012）、美罗培南-多西环素（=0.032）、青霉素-多西环素（=0.012）、青霉素-利奈唑胺（=0.026）、利福平-利奈唑胺（=0.001）和利福平-克林霉素（=0.032）。在对照组中，血液、肺和脾脏的细菌计数增加到终点。在联合治疗组中，血液和脾脏的细菌计数在 24 小时治疗后显示低/无菌落。所有联合组的 LF 均低于检测限，但对照组的 LF 仍升高。与利奈唑胺联合使用对平均 LF 水平具有最大的抑制作用。
