Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits

Abstract

Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10 5 CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone.

In vitro anti‐proliferative and in silico docking studies of heteroleptic copper(II) complexes of pyridazine‐based ligands and ciprofloxacin

“…Fluoroquinolones are formed by the substitution of a fluorine atom at position 6 and a piperazine ring at position 7 of the quinolonecarboxylic acid, which have enhanced pharmacokinetic profiles compared to quinolones . The antibiotic ciprofloxacin (1‐cyclopropyl‐6‐fluoro‐1,4‐dihydro‐4‐oxo‐7‐(piperazin‐1‐yl)quinolone‐3‐carboxylic acid) is a synthetic, broad‐spectrum, second‐generation, orally or parentally administered fluoroquinolone that has been used to treat victims infected by anthrax since 2001 . Ciprofloxacin shows anti‐proliferative and apoptotic activities in lymphoblastoid T cells (Jurkat cells), colon carcinoma (CC‐531, SW‐403 and HT‐29) and non‐small‐cell lung cancer (NCI‐H460 and A549) cell lines.…”

“…[2] The antibiotic ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(piperazin-1-yl)quinolone-3-carboxylic acid) is a synthetic, broad-spectrum, second-generation, orally or parentally administered fluoroquinolone that has been used to treat victims infected by anthrax since 2001. [3] Ciprofloxacin shows anti-proliferative and apoptotic activities in lymphoblastoid T cells (Jurkat cells), [4] colon carcinoma (CC-531, SW-403 and HT-29) [5] and non-small-cell lung cancer (NCI-H460 and A549) [6] cell lines. Ciprofloxacin exhibits a potentiating effect on cancer stem cell-like features in human non-small-cell lung cancer cells, which provokes an awareness of appropriate therapeutic strategy in cancer patients.…”

Treating Anthrax-Induced Meningitis in Rabbits

“…In 2001, PEP with ciprofloxacin or doxycycline prevented the development of anthrax in individuals with suspected or confirmed exposure (22). In addition, this treatment was effective in exposed mice (23), Guinea pigs (24), rabbits (25,26), and NHPs (27). The efficacy of treating systemic anthrax decreased with disease progression in humans (28) and animal models (24,26).…”

“…In addition, this treatment was effective in exposed mice (23), Guinea pigs (24), rabbits (25,26), and NHPs (27). The efficacy of treating systemic anthrax decreased with disease progression in humans (28) and animal models (24,26). Diagnosing meningitis in animal models is complicated and relies mainly on cerebrospinal fluid (CSF) testing for bacteria, immune cells, or elevated protein content.…”

“…We have since improved the model by infecting the rabbits by injecting the bacteria directly into the CSF via the cisterna magna (i.e., intra-cisterna magna [ICM] injection), thereby reducing the invasiveness of the infection protocol, as well as allowing drug administration via the same route. In this report, we describe the testing of ciprofloxacin, meropenem, linezolid, and clindamycin (which were found to be efficacious in treating systemic anthrax [23,24,26]) as single or combined treatments, as well as the effect of combining dexamethasone with the ciprofloxacin treatment in our animal model of induced anthrax meningitis.…”