Eliopoulos G M, Thauvin C, Gerson B, Moellering R C
Antimicrob Agents Chemother. 1985 Mar;27(3):357-62. doi: 10.1128/AAC.27.3.357.
The in vitro activity of A21978C1, a novel cyclic polypeptide antibiotic, was compared with those of vancomycin, teichomycin, and several beta-lactam antibiotics against gram-positive bacteria. The new drug was at least as active as vancomycin against all species of streptococci and staphylococci tested, including methicillin-resistant Staphylococcus aureus and penicillin-resistant pneumococci. Activity of the drug was found to be strongly correlated with the calcium concentration in test media. Against enterococci, A21978C1 was bactericidal at concentrations near the MIC (MIC for 100% of the strains, 2 micrograms/ml), but combining that drug with gentamicin resulted in bactericidal synergism by time-kill methods. Studies were undertaken to examine the mechanism of action of the drug. A21978C1 did not interact with penicillin-binding proteins of bacterial cell membranes. No direct effect of the drug on the synthesis of DNA, RNA, or protein by a susceptible strain of Streptococcus faecalis could be demonstrated. However, A21978C1 inhibited peptidoglycan synthesis in early-log-phase cultures of both Streptococcus faecalis and Staphylococcus aureus.
将新型环多肽抗生素A21978C1的体外活性与万古霉素、替考拉宁及几种β-内酰胺类抗生素针对革兰氏阳性菌的活性进行了比较。该新药对所有测试的链球菌和葡萄球菌，包括耐甲氧西林金黄色葡萄球菌和耐青霉素肺炎球菌，其活性至少与万古霉素相当。发现该药的活性与测试培养基中的钙浓度密切相关。针对肠球菌，A21978C1在接近最低抑菌浓度（100%菌株的最低抑菌浓度为2微克/毫升）时具有杀菌作用，但通过时间杀菌法将该药与庆大霉素联合使用可产生杀菌协同作用。开展了研究以考察该药的作用机制。A21978C1不与细菌细胞膜的青霉素结合蛋白相互作用。未证实该药对粪肠球菌敏感菌株的DNA、RNA或蛋白质合成有直接影响。然而，A21978C1在粪肠球菌和金黄色葡萄球菌的对数生长早期培养物中均抑制肽聚糖合成。
