Efficacy of finafloxacin in a murine model of inhalational glanders

Abstract

Burkholderia mallei, the causative agent of glanders, is principally a disease of equines, although it can also infect humans and is categorized by the U.S. Centers for Disease Control and Prevention as a category B biological agent. Human cases of glanders are rare and thus there is limited information on treatment. It is therefore recommended that cases are treated with the same therapies as used for melioidosis, which for prophylaxis, is co-trimoxazole (trimethoprim/sulfamethoxazole) or co-amoxiclav (amoxicillin/clavulanic acid). In this study, the fluoroquinolone finafloxacin was compared to co-trimoxazole as a post-exposure prophylactic in a murine model of inhalational glanders. BALB/c mice were exposed to an aerosol of B. mallei followed by treatment with co-trimoxazole or finafloxacin initiated at 24 h post-challenge and continued for 14 days. Survival at the end of the study was 55% or 70% for mice treated with finafloxacin or co-trimoxazole, respectively, however, this difference was not significant. However, finafloxacin was more effective than co-trimoxazole in controlling bacterial load within tissues and demonstrating clearance in the liver, lung and spleen following 14 days of therapy. In summary, finafloxacin should be considered as a promising alternative treatment following exposure to B. mallei.

Assessment of the Virulence of the Burkholderia mallei Strain BAC 86/19 in BALB/c Mice

“…Since glanders is primarily a respiratory or cutaneous disease [7], a switch was decided, thus altering the route of infection. The aerosol infection model is feasible [23,30] but can represent a risk to laboratory workers, as cases of human glanders have been related to this occupation [31]. Moreover, it depends on using specific apparatus, and depending on the equipment and technique used to generate the aerosol, it could be hard to generate a previous quantification of the inoculated CFU.…”

Burkholderia (Mallei and Pseudomallei) Related Zoonosis Drastic Zoonotic and Biological Warfare Potential

“…Autogenous vaccine (once) and Trimethoprim-sulphadiazine (20 mg/kg B/W P/O) for 1 month alter the disease course if given to infected horses (Al-Ani and Roberson 2007). A study in mice showed that Finafloxacin controls B. mallei at the organ level and also controls the signs which are going to develop (Barnes et al 2022). Bacteria are sensitive to co-Trimoxazole, Danofloxacin, Norfloxacin, and Chloramphenicol.…”