Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel.
PLoS One. 2020 Feb 13;15(2):e0228917. doi: 10.1371/journal.pone.0228917. eCollection 2020.
As Bacillus anthracis spores pose a proven bio-terror risk, the treatment focus has shifted from exposed populations to anthrax patients and the need for effective antibiotic treatment protocols increases. The CDC recommends carbapenems and Linezolid (oxazolidinone), for the treatment of anthrax, particularly for the late, meningeal stages of the disease. Previously we demonstrated that treatment with Meropenem or Linezolid, either as a single treatment or in combination with Ciprofloxacin, fails to protect rabbits from anthrax-meningitis. In addition, we showed that the failure of Meropenem was due to slow BBB penetration rather than low antibacterial activity. Herein, we tested the effect of increasing the dose of the antibiotic on treatment efficacy. We found that for full protection (88% cure rate) the dose should be increased four-fold from 40 mg/kg to 150 mg/kg. In addition, B. anthracis is a genetically stable bacterium and naturally occurring multidrug resistant B. anthracis strains have not been reported. In this manuscript, we report the efficacy of classical β-lactams as a single treatment or in combination with β-lactamase inhibitors in treating anthrax meningitis. We demonstrate that Ampicillin based treatment of anthrax meningitis is largely efficient (66%). The high efficacy (88-100%) of Augmentin (Amoxicillin and Clavulonic acid) and Unasyn (Ampicillin and Sulbactam) makes them a favorable choice due to reports of β-lactam resistant B. anthracis strains. Tazocin (Piperacillin and Tazobactam) proved inefficient compared to the highly efficient Augmentin and Unasyn.
由于炭疽芽孢杆菌孢子构成了已证实的生物恐怖威胁，治疗重点已经从暴露人群转移到炭疽病患者，因此需要增加有效的抗生素治疗方案。疾病预防控制中心建议使用碳青霉烯类药物和利奈唑胺（恶唑烷酮）治疗炭疽病，特别是针对疾病的晚期脑膜阶段。此前，我们已经证明，无论是单独使用美罗培南还是利奈唑胺，还是与环丙沙星联合使用，都不能保护兔子免受炭疽性脑膜炎的侵害。此外，我们还表明，美罗培南治疗失败的原因是血脑屏障穿透缓慢，而不是抗菌活性低。在此，我们测试了增加抗生素剂量对治疗效果的影响。我们发现，要实现完全保护（88%的治愈率），剂量应从 40mg/kg 增加到 150mg/kg，增加四倍。此外，炭疽杆菌是一种遗传稳定的细菌，尚未报道天然存在的多药耐药炭疽杆菌菌株。在本手稿中，我们报告了经典β-内酰胺类药物作为单一治疗或与β-内酰胺酶抑制剂联合治疗炭疽性脑膜炎的疗效。我们证明氨苄西林治疗炭疽性脑膜炎的疗效很大（66%）。氨苄西林/克拉维酸（Augmentin）和氨苄西林/舒巴坦（Unasyn）的高疗效（88-100%）由于报告了对β-内酰胺类药物耐药的炭疽杆菌菌株，因此成为一种有利的选择。哌拉西林/他唑巴坦（Tazocin）与高效的 Augmentin 和 Unasyn 相比，效果不佳。
