Closing the gaps: testing the efficacy of carbapenem and cephalosporins in treating late-stage anthrax

Anthrax is a fatal zoonotic disease caused by exposure to Bacillus anthracis spores. Treatment of systemic anthrax is usually efficient when using the right antibiotics as close as possible to exposure, preferably prior to symptoms onset as post exposure prophylaxis (PEP). The efficacy decreases as treatment is initiated later in disease progression. The CDC in its guidelines divides anthrax treatment to three different indications according to the progression of the disease: PEP, systemic and systemic with indications of CNS infection. While the prognosis of PEP or early treatment of systemic anthrax is very good, ingress of the bacteria into the CNS significantly decreases treatment efficacy, creating a substantial clinical challenge. Since anthrax in humans is rare, the CDC recommendations are mainly based on animal model experiments and data obtained from patients infected with other pathogens. Here we use rabbits to test the efficacy of the combined treatment of Meropenem and Doxycycline which is the first choice in the CDC recommendations for treating systemic patients with indication of CNS infection. In addition, we test the efficacy of the first-generation cephalosporin, cefazolin, in treating the different stages of the disease. We found that the combination of Doxycycline and Meropenem is highly effective in treating rabbits in our inhalation and CNS infection models. Cefazoline was efficient only as PEP or systemic stage treatment but not CNS infected animals. Our findings support the CDC recommendation of using a combination of Doxycycline and Meropenem for systemic patients with or without indications for CNS infection. We found that Cefazoline is a decent choice for PEP or early sage systemic disease but recommend considering using this antibiotic only if all other options are not available.