Αρχειοθήκη ιστολογίου

Δευτέρα 16 Απριλίου 2018

Treating Anthrax-Induced Meningitis in Rabbits [PublishAheadOfPrint]

Treatment of Anthrax is challenging, especially during the advanced stages of the disease. Recently the CDC updated its recommendations for post-exposure prophylaxis and treatment of exposed populations (pre and post symptoms onset). These recommendations distinguished, for the first time, between the systemic disease with and without meningitis, a common and serious complication of anthrax. The CDC considers all systemic patients as meningeal unless positively proven otherwise. The treatment of patients suffering from systemic Anthrax with suspected or confirmed meningitis includes the combination of three antibiotics -- a fluoroquinolone (Levofloxacin or Ciprofloxacin), a β-lactam (Meropenem or Imipenem) and a protein-synthesis inhibitor (Linezolid or Clindamycin). In addition, treatment with an antitoxin (αPA antibodies) and Dexamethasone should also be applied. Since the efficacy of most of these treatments was not demonstrated, especially in meningeal animal models, we developed an Anthrax-meningitis model in rabbits and tested several of these recommendations. We demonstrate that in this model, Ciprofloxacin, Linezolid and Meropenem are ineffective as single treatments while Clindamycin is highly effective. Furthermore, combined treatments of Ciprofloxacin and Linezolid, or Ciprofloxacin and Dexamethasone failed in treating meningeal rabbits. We demonstrate that Dexamethasone actually hinders the blood brain barrier penetration of antibiotics, reducing the effectiveness of antibiotic treatment of Anthrax-meningitis in the rabbit model.



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