title: Lack of emergence of significant resistance in vitro and in vivo to the new azalide antibiotic azithromycin.
abstract: In vitro experiments were performed in which 6 to 12 strains of Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae and Enterobacteriaceae were passaged nine times in sub-lethal concentrations of azithromycin or control antibiotics. Streptococcus pyogenes and Staphylococcus aureus quickly became resistant to rifampin as the MIC90 increased from 0.1 to greater than 50 micrograms/ml for both species. The MIC90 of azithromycin, erythromycin, amoxicillin and cefaclor increased by three dilutions for Staphylococcus aureus. The MIC values of azithromycin for Streptococcus pyogenes, Haemophilus influenzae and Enterobacteriaceae strains did not change significantly. However, for Haemophilus influenzae and the Enterobacteriaceae strains, the MIC values of erythromycin and oral cephalosporins increased four-fold. In the in vivo experiments, mice infected with Staphylococcus aureus or Escherichia coli contaminated sutures were administered azithromycin for three days, and on day 6 viable bacterial cells were recovered from the infection site. The sustained tissue concentrations of azithromycin indicated that the organisms would have been continuously exposed to azithromycin at the site of infection. Colonies isolated from azithromycin-treated and non-treated mice were cultured and their susceptibility to azithromycin compared. The azithromycin MIC values for Staphylococcus aureus cultures from treated and non-treated animals were identical. The azithromycin MICs for Escherichia coli recovered from treated animals were on average, less than one dilution higher than for control cultures. Emergence of significant resistance to azithromycin in the laboratory was not observed with the pathogens tested.
authors.affiliation: Central Research Division, Pfizer Inc., Groton, CT 06340.
authors.forename: J A
authors.initials: JA
authors.lastname: Retsema
authors.forename: A E
authors.initials: AE
authors.lastname: Girard
authors.forename: L A
authors.initials: LA
authors.lastname: Brennan
authors.forename: C R
authors.initials: CR
authors.lastname: Cimochowski
authors.forename: J A
authors.initials: JA
authors.lastname: Faiella
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017963:Azithromycin; D001431:Bacteriological Techniques; D004352:Drug Resistance, Microbial; D004755:Enterobacteriaceae / Q000187:drug effects; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D013536:Suture Techniques
chemical_list: D000900:Anti-Bacterial Agents; D004917:Erythromycin; D017963:Azithromycin