Susceptibility and resistance emergence studies with macrolides.
An extended elimination half-life and good tissue penetration enable oral azithromycin to attain high and prolonged concentrations in infected tissues, yielding high antibacterial activity in vivo. It has been suggested, however, that prolonged subinhibitory concentrations of azithromycin from 2 to 4 weeks after therapy may lead to the emergence of azithromycin resistance in vivo, compared with other macrolide antibiotics. Data from two types of in vitro susceptibility studies, an animal tissue infection model, and a clinical pediatric study demonstrate that prolonged tissue concentrations of azithromycin are unlikely to lead to the emergence of resistance in the clinical setting. Further, data from in vitro susceptibility studies indicate that resistance to macrolides, and azithromycin in particular, is significantly over-estimated for bacterial strains incubated in the presence of CO2.
Retsema
J A
JA
Pfizer Inc., Central Research Division, Groton, CT 06340, USA.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000502:physiology; D002648:Child; D002986:Clinical Trials as Topic; D004352:Drug Resistance, Microbial; D006801:Humans; D008826:Microbial Sensitivity Tests; D012141:Respiratory Tract Infections / Q000382:microbiology*; D013291:Streptococcus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D002245:Carbon Dioxide; D017963:Azithromycin