Efficacy of Doxycycline as monotherapy or in combination with Levofloxacin in treating late-stage systemic anthrax in NHP

Abstract Bacillus anthracis spores pose a major biosecurity threat, in light of their use in several documented bio-terror attacks and the fact that it was weaponized. The absence of specific and accurate treatment instructions in the 2001 anthrax letter attacks and the poor prognosis of patient receiving noneffective treatment, emphasized the need for reliable guidelines for treating exposed(prophylaxis) or symptomatic populations. The recent 2024 CDC guidelines for treating systemic anthrax recommend a combined treatment of a tetracycline (Minocycline or Doxycycline) with Meropenem or a fluoroquinolone. These recommendations differ from the 2001 or 2015 updates, and in the absence of significant clinical data, rely on animal studies. Previously we demonstrated, based on a rabbit model, that these recommendations are efficient in treating various stages of anthrax, ranging from post exposure prophylaxis, through systemic to involvement of the CNS. Herein we confirm our rabbit results by demonstrating the efficacy of Doxycycline as a monotherapy or in combination with Levofloxacin in treating late-stage systemic anthrax in non-human primates (NHP), in a trigger to treat type of experiment. Our experiments show high efficacy of the mono or combined therapy. Altogether, these results support the CDC guidelines by demonstrating the efficacy of this treatment in a second highly relevant NHP model. Competing Interest Statement The authors have declared no competing interest. Footnotes ↵+ H.L. haiml{at}iibr.gov.il, S.W. shayw{at}iibr.gov.il The manuscript text was extended to clarify and discus the results.