title: Comparison of in vitro activities of ABT-773 and telithromycin against macrolide-susceptible and -resistant streptococci and staphylococci.
abstract: The activity of a new ketolide, ABT-773, was compared to the activity of the ketolide telithromycin (HMR-3647) against over 600 gram-positive clinical isolates, including 356 Streptococcus pneumoniae, 167 Staphylococcus aureus, and 136 Streptococcus pyogenes isolates. Macrolide-susceptible isolates as well as macrolide-resistant isolates with ribosomal methylase (Erm), macrolide efflux (Mef), and ribosomal mutations were tested using the NCCLS reference broth microdilution method. Both compounds were extremely active against macrolide-susceptible isolates, with the minimum inhibitory concentrations at which 90% of the isolates tested were inhibited (MIC90s) for susceptible streptococci and staphylococci ranging from 0.002 to 0.03 microg/ml for ABT-773 and 0.008 to 0.06 microg/ml for telithromycin. ABT-773 had increased activities against macrolide-resistant S. pneumoniae (Erm MIC90, 0.015 microg/ml; Mef MIC90, 0.12 microg/ml) compared to those of telithromycin (Erm MIC90, 0.12 microg/ml; Mef MIC90, 1 microg/ml). Both compounds were active against strains with rRNA or ribosomal protein mutations (MIC90, 0.12 microg/ml). ABT-773 was also more active against macrolide-resistant S. pyogenes (ABT-773 Erm MIC90, 0.5 microg/ml; ABT-773 Mef MIC90, 0.12 microg/ml; telithromycin Erm MIC90, >8 microg/ml; telithromycin Mef MIC90, 1.0 microg/ml). Both compounds lacked activity against constitutive macrolide-resistant Staphylococcus aureus but had good activities against inducibly resistant Staphylococcus aureus (ABT-773 MIC90, 0.06 microg/ml; telithromycin MIC90, 0.5 microg/ml). ABT-773 has superior activity against macrolide-resistant streptococci compared to that of telithromycin.
authors.affiliation: Discovery and Clinical Microbiology, Infectious Diseases Research, Abbott Laboratories, Abbott Park, Illinois 60064, USA. dee.shortridge@abbott.com
authors.forename: Virginia D
authors.initials: VD
authors.lastname: Shortridge
authors.forename: Ping
authors.initials: P
authors.lastname: Zhong
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Cao
authors.forename: Jill M
authors.initials: JM
authors.lastname: Beyer
authors.forename: Laurel S
authors.initials: LS
authors.lastname: Almer
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Ramer
authors.forename: Stella Z
authors.initials: SZ
authors.lastname: Doktor
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D048628:Ketolides; D018942:Macrolides; D008826:Microbial Sensitivity Tests; D012141:Respiratory Tract Infections / Q000382:microbiology; D012270:Ribosomes / Q000378:metabolism; D013210:Staphylococcus / Q000187:drug effects* / Q000378:metabolism; D013291:Streptococcus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D004917:Erythromycin; C405499:cethromycin; C106791:telithromycin