The activity of grepafloxacin in two murine models of Mycobacterium avium infection

The activity against Mycobacterium avium complex (MAC) of varying doses of grepafloxacin (GRE; 25 mg/kg, 50 mg/kg, 100 mg/kg, and 200 mg/kg) were compared to clarithromycin (CLA; 100 mg/kg and 200 mg/kg), ethambutol (EMB; 100 mg/kg), and rifabutin (RBT; 10 mg/kg) using an intranasal (IN) Infection model compared to an intravenous (IV) Infection model. Beige mice (C57BL6/J-Lyst bg J/+) were infected intranasally with about 10(6) organisms and for the IV model about 10(7) organisms. Treatment for both models was started 1 week postinfection and given by gavage 5 days/week for 4 weeks. At the initiation of therapy, an early control group was killed to determine the initial organism load. Three days following the completion of therapy, drug-treated groups of mice and the late control group were killed and the response to therapy measured. The most effective agents were CLA and RBT. GRE and EMB had modest activities in both the IN and the IV models. A matched comparison between IN and IV challenges for each of the agents used revealed greater suppression of MAC in the IN model compared to the IV model.