Jamjian C, Biedenbach D J, Jones R N
Department of Pharmaceutical Care, University of Iowa Hospitals and Clinics, Iowa City 52242, USA.
Antimicrob Agents Chemother. 1997 Feb;41(2):454-9. doi: 10.1128/AAC.41.2.454.
Ketolides, a novel macrolide subclass, possess a mode of action that is similar to that of structurally related macrolide-lincosamide-streptogramin (MLS) compounds. By using reference in vitro tests, the in vitro activity of RU-64004 was compared to those of six other MLS compounds against more than 800 clinical pathogens, including 356 gram-positive organisms. The spectrum of activity of the ketolide was most similar to that of clindamycin versus staphylococci and streptococci and superior to those of all macrolides tested against oxacillin-resistant staphylococci and vancomycin-resistant (vanA, vanB, and vanC) enterococcal isolates. The activity of the ketolide was greater than those of the macrolides, azalides, or clindamycin tested against vancomycin-susceptible enterococci (MICs at which 90% of isolates are inhibited [MIC90S], 0.25 to 4 micrograms/ml), penicillin-resistant pneumococci (MIC90, 0.25 micrograms/ml), and most beta-hemolytic streptococci. All Streptococcus pneumoniae and beta-hemolytic streptococcus strain were inhibited by ketolide concentrations of < or = 0.25 micrograms/ml. Against 165 erythromycin-resistant strains, RU-64004 inhibited (MICs, < or = 0.5 micrograms/ml) approximately one-third of staphylococci, all streptococci, and slightly more than one-half of the enterococci. Quinupristin-dalfopristin (a streptogramin combination) was active against all tested isolates with the exception of non-Enterococcus faecium enterococci, against which the ketolide exhibited greater potency (MIC50S, 0.03 to 2 micrograms/ml). The ketolide was also active against Haemophilus influenzae (MIC90, 2 micrograms/ml), Moraxella catarrhalis (MIC90, 0.12 micrograms/ml), pathogenic Neisseria spp. (MIC90, 0.5 micrograms/ml), and many gram-positive anaerobes (MIC90, 0.5 micrograms/ml). RU-64004 may enhance the role of macrolide drugs in the treatment of some serious infections caused by MLS-resistant gram-positive organisms.
酮内酯类是新型大环内酯子类，其作用方式与结构相关的大环内酯-林可酰胺-链阳菌素（MLS）化合物相似。通过使用参考体外试验，将RU-64004与其他六种MLS化合物针对800多种临床病原体（包括356种革兰氏阳性菌）的体外活性进行了比较。酮内酯的活性谱与克林霉素针对葡萄球菌和链球菌的活性谱最为相似，且优于所有测试的大环内酯类药物针对耐苯唑西林葡萄球菌和耐万古霉素（vanA、vanB和vanC）肠球菌分离株的活性。酮内酯针对万古霉素敏感肠球菌（90%分离株被抑制时的MIC[MIC90S]，0.25至4微克/毫升）、耐青霉素肺炎链球菌（MIC90，0.25微克/毫升）和大多数β溶血性链球菌的活性大于所测试的大环内酯类、氮杂内酯类或克林霉素。所有肺炎链球菌和β溶血性链球菌菌株在酮内酯浓度≤0.25微克/毫升时均被抑制。针对165株耐红霉素菌株，RU-64004抑制（MIC，≤0.5微克/毫升）约三分之一的葡萄球菌、所有链球菌以及略超过一半的肠球菌。奎奴普丁-达福普汀（一种链阳菌素组合）对所有测试分离株均有活性，但对非粪肠球菌的肠球菌除外，针对该菌酮内酯表现出更强的效力（MIC50S，0.03至2微克/毫升）。酮内酯对流感嗜血杆菌（MIC90，2微克/毫升）、卡他莫拉菌（MIC90，0.12微克/毫升）、致病性奈瑟菌属（MIC90，0.5微克/毫升）以及许多革兰氏阳性厌氧菌（MIC90，0.5微克/毫升）也有活性。RU-64004可能会增强大环内酯类药物在治疗某些由耐MLS革兰氏阳性菌引起的严重感染中的作用。
