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.

Keywords: Burkholderia mallei; co-trimoxazole; finafloxacin; glanders; mouse models.

FIGURE 1

The percentage survival of mice following challenge with aerosolized B. mallei. Mice were challenged with a mean retained dose of 1.52 × 10⁴ CFU of B. mallei by the inhalational route and treated with finafloxacin (37.5 mg/kg) every 8 h or co-trimoxazole (78 mg/kg) every 12 h by the oral route. Control animals received vehicle by the oral route every 8 h. Regimens were initiated at 24 h post-challenge and continued for 14 days.

FIGURE 2

The bacterial load in organs of mice challenged with B. mallei and treated with antibiotics. Bacterial counts (CFU/g) in the spleen, livers and lungs of mice following 1 day of antibiotic treatment (A), 14 days of antibiotic treatment (B) or at the end of study day 65 (brains also harvested) (C). Therapy was initiated at 24 h post-challenge and continued for 14 days. Treatment was with finafloxacin (37.5 mg/kg) every 8 h or co-trimoxazole (78 mg/kg) every 12 h delivered by the oral route. LoD, limit of detection ***p < 0.001, *p < 0.05.

FIGURE 3

The weight loss and clinical scores of mice challenged with B. mallei and treated with antibiotics. Mice were challenged with a mean retained dose of 1.52 × 10⁴ CFU of B. mallei. Therapy was initiated at 24 h post-challenge with finafloxacin (37.5 mg/kg) every 8 h or co-trimoxazole (78 mg/kg) every 12 h by the oral route. Control animals received vehicle by the oral route. Treatment was continued for 14 days. The mean percentage weight loss when compared to the original bodyweight is shown for each treatment group (A) and the mean clinical score (B).