Efficacy of a novel perfluorocarbon-based intrapulmonary drug delivery system

Introduction: We sought to determine the efficacy of a novel intrapulmonary perfluorocarbon (PFC) based antibiotic delivery system in a rat model of pneumococcal pneumonia. Methods: Wistar rats (400-500 g) were inoculated with 8x10' type 3 pneumococcus via direct intratracheal (IT) injection. Twenty-four h after inoculation, rats received no treatment (control, n=15), 10 mg IM ampicillin (AMP, n =10), 10 ml lavage with an AMP containing (1 mg/ml) microparticulate dispersion in PFC (AMPPFC; Alliance Pharmaceutical Corp.; n=ll). Animals were monitored daily for survival for 10 days. AMP concentrations, were determined in serum and lung homogenates using a bioassay. The log-rank test with Bonferroni's correction was used to determine differences in mortality among groups. The null hypothesis was rejected for a critical p<0.017. Results: Mortality was significantly higher in controls than AMPPFC (100% vs 18%, p < 0.017). There was a trend favoring treatment with AMPPFC compared to AMP (18% vs 70% mortality, p<0.019). The table shows serum and lung antibiotic concentrations (n=2) Time (h) AMP (jig/ml) AMPPFC Qig/ml) Serum Lung Serum Lung 1 15 2 15 500 2 1 1 2 120 3 0 0 1 60 4 0 0 2 50 8 0 0 0 15 24 0 0 0 10 48 0 0 0 3 72 0 0 0 2 Conclusions: PFC-based IT antibiotic microparticulate formüations may be more effect than systemic antibiotic therapy alone in the treatment of severe pneumonia

Liquid ventilation with perflubron in the treatment of rats with pneumococcal pneumonia.

OBJECTIVE: To determine the efficacy of liquid ventilation using a medical-grade perfluorocarbon (perflubron) combined with parenteral or intratracheal antibiotics in a rat model of pneumonia. DESIGN: Prospective, laboratory investigation. SETTING: Experimental laboratory in a university medical center. SUBJECTS: Wistar rats (n = 112). INTERVENTIONS: One day after intratracheal inoculation with Streptococcus pneumoniae, rats received one of five experimental treatments or no treatment (control): modified liquid ventilation (MLV), intramuscular ampicillin, MLV plus intramuscular ampicillin, MLV with intratracheal ampicillin, or MLV plus ampicillin PulmoSpheres. MEASUREMENTS AND MAIN RESULTS: Animals receiving MLV plus intramuscular ampicillin, MLV with intratracheal ampicillin, or MLV plus ampicillin PulmoSpheres had significantly improved 10-day survival rates (85%, 72%, and 72%, respectively) compared with all other groups (0% to 25%). CONCLUSIONS: MLV in combination with either intramuscular, intratracheal, or PulmoSpheres ampicillin improved survival as compared with MLV alone or the same dose of antibiotics delivered intramuscularly