Inhaled liposomal ciprofloxacin protects against lethal tularemia in the common marmoset.

Abstract

is a gram-negative, intracellular bacterium that causes the disease tularemia. Tularemia is prevalent in North America, Europe, and Asia and is typically treated with injected and orally administered antibiotics, including streptomycin, gentamicin, doxycycline, and ciprofloxacin, administered for 10 to 21 days. New therapeutic options are required to reduce the potential of a relapse of disease. Inhaled liposomal-encapsulated ciprofloxacin has demonstrated protection in a murine model of tularemia. The efficacy was further assessed in a nonhuman primate model of tularemia. Mixed-sex common marmosets were challenged withby the inhalational route, and the efficacy of ciprofloxacin delivered by either the inhalational (Apulmiq liposomal formulation) or oral route was compared. Antibiotics were initiated either at 24 h post-challenge (post-exposure prophylaxis) or at the onset of fever (treatment) and continued for 7 days. All control (untreated) animals succumbed to infection by 8 days post-challenge. All animals that received antibiotics, by either route, survived the duration of the study, with bacterial clearance in all but one animal that received inhalational ciprofloxacin. Antibiotic treatment also reduced the physiological and immunological responses observed when compared to animals that received no antibiotics. Histological changes in the lungs were less frequent, although mild, resolving lesions were present in animals treated with ciprofloxacin delivered at the onset of fever by either route.