Aerosol treatment with cefoperazone or gentamicin protects granulocytopenic mice from acute Pseudomonas aeruginosa pneumonia

The usefulness of the aerosol route for delivery of either cefoperazone (CEF) or gentamicin (GEN) for the treatment of acute Pseudomonas aeruginosa pneumonia was assessed in mice rendered granulocytopenic by treatment with 200 mg/kg cyclophosphamide. Aerosol delivery of CEF (60 μg/ml final concentration in lung homogenate) was significantly more effective (90% survival) than the single intraperitoneal (i.p.) inoculation of 640 mg/kg CEF (0% survival) (P < 0.001). Similarly, aerosol delivery of gentamicin (11 μg/ml final concentration in lung homogenate) was significantly more effective (100% survival) than single or multiple inoculation of a total i.p. dose of 16 mg/kg (0% survival) (P < 0.001). Pulmonary half-life of both antibiotics after aerosol administration was higher than that obtained after i.p. inoculation.