Relevance of Chlamydia pneumoniae murine pneumonitis model to evaluation of antimicrobial agents.
A mouse model of Chlamydia pneumoniae pneumonitis was established in outbred MF1 mice immunosuppressed with cyclophosphamide. Following intranasal inoculation with 2.2 x 10(3) inclusion-forming units of C. pneumoniae TW-183 per mouse, chlamydiae were culturable from the lungs for at least 29 days. Progressive subacute pneumonitis with perivascular and peribronchial lymphoid cell hyperplasia was observed, and C. pneumoniae organisms were located in consolidated areas of tissue by immunocytochemistry. Mice were treated orally, commencing at 8 days after infection, with clinically achievable concentrations of amoxicillin-clavulanate or ciprofloxacin (three times daily for 7 days), ofloxacin, doxycycline, or erythromycin (twice daily for 7 days), or azithromycin (once daily for 4 days). Despite disparate antichlamydial activity in cell culture and different pharmacokinetic properties in infected animals, all treatments reduced the chlamydial load in the lungs (P < 0.05) when the loads were evaluated by culture at 1 and 10 days after the cessation of dosing, and this was reflected in the histopathological and immunocytochemistry scores. There was no significant difference between these treatments, and C. pneumoniae TW-183 was eradicated from the majority but not from all mice. These results confirm the limited clinical data available to date. In conclusion, a range of oral antimicrobial agents commonly used for the treatment of community-acquired respiratory infection was found to be efficacious in this experimental model of C. pneumoniae pneumonitis, which may therefore be of utility in chemotherapy and follow-up studies.
SmithKline Beecham Pharmaceuticals, Betchworth, Surrey, United Kingdom.
N D
ND
Masson
C D
CD
Toseland
A S
AS
Beale
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D016993:Chlamydophila pneumoniae; D017714:Community-Acquired Infections / Q000188:drug therapy / Q000382:microbiology; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008826:Microbial Sensitivity Tests; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D013045:Species Specificity
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide