Noncompromised penicillin-resistant pneumococcal pneumonia CBA/J mouse model and comparative efficacies of antibiotics in this model.
The present study confirms that CBA/J mice are susceptible to several clinical isolates of Streptococcus pneumoniae, including four of five penicillin-susceptible and all five penicillin-resistant strains tested, thus providing the first noncompromised animal model for penicillin-resistant S. pneumoniae pneumonia. In this model, doses of penicillin G of 0.6 mg/kg of body weight given six times at 1-h intervals produced effective pulmonary clearance of a penicillin-susceptible strain (penicillin G MIC, 0.015 microgram/ml), while doses of 40 mg/kg given six times at 1-h intervals were required to clear a penicillin-resistant strain (penicillin G MIC, 1 microgram/ml). Imipenem (MIC, 0.25 microgram/ml) was the most active antibiotic tested against the penicillin-resistant strain, with a calculated dose of 0.42 mg/kg given six times at 1-h intervals, resulting in a 2-log decrease in the number of pulmonary bacteria. Comparable effects were seen with vancomycin (MIC, 0.5 microgram/ml), cefotaxime (MIC, 0.5 microgram/ml), and penicillin G at doses of 3.3, 5.5, and 31.0 mg/kg given six times at 1-h intervals, respectively. The pharmacokinetic profile of vancomycin in infected lungs was superior to those of the other antibiotics, especially in regard to the elimination half-life (215.4 min for vancomycin versus 15.0, 14.5, and 14.5 min for penicillin G, cefotaxime, and imipenem, respectively). Both imipenem and vancomycin allowed 90% survival when 40-mg/kg doses were administered twice a day beginning 5 days after infection. Survival rates with penicillin G (160-mg/kg doses) and cefotaxime (40-mg/kg doses) were 40 and 30%, respectively, while no saline-treated mice survived. The present study shows that the CBA/J mouse pneumonia model may be useful for evaluating antibiotic efficacies against penicillin-resistant pneumococcal pneumonia in immunocompetent individuals. Our data suggest that imipenem and vancomycin may be the most active agents against penicillin-resistant S. pneumoniae pneumonia.
Tateda
K
K
Department of Microbiology, Toho University School of Medicine, Tokyo, Japan. kazu@sirius.med.toho-u.ac.jp
Takashima
K
K
Miyazaki
H
H
Matsumoto
T
T
Hatori
T
T
Yamaguchi
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002439:Cefotaxime / Q000493:pharmacokinetics / Q000627:therapeutic use; D004195:Disease Models, Animal; D015378:Imipenem / Q000493:pharmacokinetics / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D010400:Penicillin G / Q000493:pharmacokinetics / Q000627:therapeutic use; D010403:Penicillin Resistance; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D013045:Species Specificity; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D014640:Vancomycin / Q000493:pharmacokinetics / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D014640:Vancomycin; D015378:Imipenem; D002439:Cefotaxime; D010400:Penicillin G