Shortridge Virginia D, Zhong Ping, Cao Zhensheng, Beyer Jill M, Almer Laurel S, Ramer Nancy C, Doktor Stella Z, Flamm Robert K
Discovery and Clinical Microbiology, Infectious Diseases Research, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Antimicrob Agents Chemother. 2002 Mar;46(3):783-6. doi: 10.1128/AAC.46.3.783-786.2002.
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.
将新型酮内酯类药物ABT - 773的活性与酮内酯类药物泰利霉素（HMR - 3647）针对600多株革兰氏阳性临床分离株的活性进行了比较，这些分离株包括356株肺炎链球菌、167株金黄色葡萄球菌和136株化脓性链球菌。使用美国国家临床实验室标准委员会（NCCLS）参考肉汤微量稀释法对大环内酯类敏感分离株以及具有核糖体甲基化酶（Erm）、大环内酯外排（Mef）和核糖体突变的大环内酯类耐药分离株进行了测试。两种化合物对大环内酯类敏感分离株均具有极高活性，对于敏感链球菌和葡萄球菌，ABT - 773的90%受试分离株被抑制时的最低抑菌浓度（MIC90s）范围为0.002至0.03微克/毫升，泰利霉素为0.008至0.06微克/毫升。与泰利霉素相比，ABT - 773对大环内酯类耐药肺炎链球菌（Erm MIC90，0.015微克/毫升；Mef MIC90，0.12微克/毫升）的活性增强（泰利霉素的Erm MIC90，0.12微克/毫升；Mef MIC90，1微克/毫升）。两种化合物对具有rRNA或核糖体蛋白突变的菌株均有活性（MIC90，0.12微克/毫升）。ABT - 773对大环内酯类耐药化脓性链球菌也更具活性（ABT - 773的Erm MIC90，0.5微克/毫升；ABT - 773的Mef MIC90，0.12微克/毫升；泰利霉素的Erm MIC90，>8微克/毫升；泰利霉素的Mef MIC90，1.0微克/毫升）。两种化合物对组成型大环内酯类耐药金黄色葡萄球菌均无活性，但对诱导型耐药金黄色葡萄球菌具有良好活性（ABT - 773的MIC90，0.06微克/毫升；泰利霉素的MIC90，0.5微克/毫升）。与泰利霉素相比，ABT - 773对大环内酯类耐药链球菌具有更强的活性。
