Abstract

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.

Highlights

  • Bacillus anthracis, the etiological cause of Anthrax, is a gram-positive spore forming bacterium

  • Efficacy of Ampicillin and Augmentin in treating anthrax central nervous system (CNS) infections To test the efficacy of Ampicillin and Augmentin (Amoxicillin/Clavulanate) we used our rabbit CNS infection model

  • Rabbits were infected by intra-cisterna magna (ICM) injection with capsular vegetative Vollum strain bacteria

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Summary

Introduction

The etiological cause of Anthrax, is a gram-positive spore forming bacterium. Anthrax is a zoonotic disease that usually afflicts herbivores and is usually transferred to humans by contact with contaminated animal products [1, 2]. The infecting form of B. anthracis is the spore that can infect the host via three major routes; skin, gastrointestinal tract and the respiratory system [3]. The route of infection determines the type of disease and the outcome of the infection. Contact of spores with damaged skin will cause a local lesion (eschar), that in the absence of treatment will remain local and resolve spontaneously in 70–. February 13, 2020 β-lactam treatment of Anthrax-induced meningitis

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