Efficacy of Continuous Versus Intermittent Administration of Penicillin G in Streptococcus Pneumoniae Pneumonia in Normal and Immunodeficient Rats

An experimental Streptococcus pneumoniae pneumonia was used to study the influence of continuous versus intermittent administration of penicillin G on therapeutic efficacy in normal rats and in rats whose phagocytic capacities were impaired by decomplementation with cobra venom factor. Response to antibiotic treatment was evaluated with respect to numbers of bacteria in left lung, blood and pleural fluid. Penicillin treatment was started 36 h after bacterial inoculation, and continued for four days. With intermittent intramuscular administration of penicillin normal rats were cured after daily doses of 4 mg/kg at 12 h intervals, whereas decomplemented rats recovered only after daily doses of 100 or 102 mg/kg at 12 h or 8 h intervals, respectively. When penicillin was administered by way of continuous infusion, daily doses of 3.5 mg/kg were required for a cure of infections in both normal rats and in decomplemented rats. This treatment resulted in a constant level of 0.05 micrograms of penicillin per ml, which was slightly above the minimum bactericidal concentration for the infecting strain. These findings show that maintenance of bactericidal levels of penicillin were particularly important in curing severe infection in rats with impaired defense.