Therapeutic Efficacies of Penicillin G, Cefotaxime, and Imipenem/Cilastatin against Penicillin-Resistant Pneumococcal Pneumonia in CBA/J Mice

Abstract

We compared the therapeutic efficacies of penicillin G (PCG), cefotaxime (CTX), and imipenem/cilastatin (IPM/CS) against penicillin-resistant<i>Streptococcus pneumoniae</i> pneumonia in CBA/J mice. In pneumonia induced by strain TUH39 (PCG MIC; 0.063μg/mL), eight 2.5mg/kg doses of PCG administered at 1.5 hour intervals beginning 36 hours after infection reduced the number of bacteria in the lungs below the limit of detection. In contrast, a similar regimen failed to lower the number of organisms following infection with strain TUM741 (PCG MIC; 1μg/mL); however, PCG doses of 8 × 10 and 8 × 40mg/kg reduced bacterial numbers in a dose-dependent manner. CTX (MIC; 0.5μg/mL) and IPM/CS (MIC; 0.125μg/mL) at 6 × 40mg/kg were more effective than PCG at the same dose against strain TUM741 pneumonia; these antibiotics eradicated bacteria in lungs of 2 out of 5 and 5 out of 5 mice, respectively. In accord with the pulmonary clearance results, survival of mice treated with PCG (6 × 40 and 6 × 160mg/kg), CTX (6 × 40mg/kg) and IPM/CS (6 × 40mg/kg) were 30%, 80%, 40% and 100%, respectively. Pharmacokinetic analysis in lungs revealed that IPM/CS was superior to CTX and PCG in several parameters. These results demonstrate therapeutic responses to CTX, IPM/CS and high-dose PCG in a CBA/J mouse model of penicillin-resistant pneumococcal pneumonia. Results with IPM/CS were particularly favorable, suggesting this antibiotic combination as a potential first-line treatment for penicillin-resistant<i>S. pneumoniae</i> pneumonia.