The comparative activity of azithromycin, macrolides and amoxycillin against streptococci in experimental infections.
Since serious sequelae may follow streptococcal infections, eradication is viewed as necessary for successful therapy. Studies were therefore conducted to compare the effectiveness of azithromycin with other macrolide antibiotics and amoxycillin to eliminate these organisms in experimental localized infections. In a Streptococcus pneumoniae lung infection induced by transtracheal challenge, the pathogen was not recovered after therapy with azithromycin (ED50 7.9 mg/kg), while clarithromycin was not effective (ED50 > 100 mg/kg). However, in a S. pneumoniae middle ear infection, azithromycin and clarithromycin were effective (ED50 2.9 and 6.3 mg/kg, respectively) in eradicating the pathogen from this closed space infection. Against a localized Streptococcus pyogenes infection (implanted inoculated disc), azithromycin effectively eradicated the pathogen, while clarithromycin, roxithromycin and erythromycin did not. Eradication of a viridans streptococcus or Streptococcus gordonii (formerly Streptococcus sanguis) from heart tissue in experimental bacterial endocarditis was also evaluated. Azithromycin given prophylactically or therapeutically was efficacious in eliminating the viridans streptococcus and S. gordonii in the bacterial endocarditis model of infection; erythromycin was only marginally effective in the same studies. All studies provided evidence of the bactericidal action of azithromycin in vivo and demonstrated the ability of the compound to eradicate streptococcal pathogens in localized infections.
Central Research Division, Pfizer Inc., Groton, CT 06340.
A E
AE
Girard
C R
CR
Cimochowski
J A
JA
Faiella
D000658:Amoxicillin / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin; D017291:Clarithromycin / Q000494:pharmacology; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000188:drug therapy / Q000382:microbiology; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005849:Gerbillinae; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010033:Otitis Media / Q000188:drug therapy / Q000382:microbiology; D011008:Pneumococcal Infections / Q000188:drug therapy; D011014:Pneumonia / Q000188:drug therapy; D051381:Rats; D015575:Roxithromycin / Q000494:pharmacology; D013290:Streptococcal Infections / Q000188:drug therapy*; D013297:Streptococcus pyogenes
D000900:Anti-Bacterial Agents; D015575:Roxithromycin; D004917:Erythromycin; D000658:Amoxicillin; D017963:Azithromycin; D017291:Clarithromycin