Comparison of selection for mutants with reduced susceptibility to ABT-773, erythromycin and rifampicin in respiratory tract pathogens.
Attempts were made to select mutants on agar media containing the new ketolide ABT-773, erythromycin or rifampicin, at concentrations above the MICs, from Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae, including erythromycin-resistant strains. ABT-773 did not select for mutants in four strains, whereas in eight strains the frequencies at 72 h were < or = 10(-9). ABT-773 MICs were 0.015-4 mg/L for mutants, except those selected from inducible Erm(A) S. aureus. Mutants selected on ABT-773 or erythromycin were cross-resistant to ABT-773, erythromycin and, sometimes, clindamycin. The susceptibility profiles indicate that different mutations were selected and that ABT-773 and erythromycin may interact with the ribosome differently.
Nilius
Angela M
AM
Infectious Diseases Research, Abbott Laboratories, Abbott Park, IL 60064-3537, USA. angela.nilius@abbott.com
Hensey-Rudloff
Dena M
DM
Reimann
Megan A
MA
Flamm
Robert K
RK
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics*; D003470:Culture Media; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006193:Haemophilus influenzae / Q000187:drug effects; D048628:Ketolides; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012141:Respiratory Tract Infections / Q000382:microbiology*; D012293:Rifampin / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D003470:Culture Media; D048628:Ketolides; D004917:Erythromycin; C405499:cethromycin; D012293:Rifampin