Liebowitz L D, Saunders J, Chalkley L J, Koornhof H J
South African Medical Research Council, School of Pathology, University of the Witwatersrand, Johannesburg.
Antimicrob Agents Chemother. 1988 Jan;32(1):24-6. doi: 10.1128/AAC.32.1.24.
Isolates of Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium, and coagulase-positive and -negative staphylococci were investigated for their abilities, in vitro, to develop resistance to LY146032. Exposure of the organisms to incremental concentrations of LY146032 resulted in MICs 8- to 32-fold higher than those for the original isolates. After three passages on antibiotic-free medium, the high MICs were maintained for the coagulase-negative staphylococci and pneumococci, with a twofold decrease observed for the enterococci and a fourfold decrease observed for Staphylococcus aureus. The frequency of spontaneous emergence of resistance was highest with S. pneumoniae (1.2 X 10(-6) at 16 times the original MIC) and lowest with S. aureus (7.0 X 10(-10) at 8 times the original MIC). For bacteria For bacteria surviving time-kill studies MICs were also higher than were those for the original isolates. Exposure to LY146032 in vitro selected for strains with decreased susceptibilities to the antimicrobial agent. However, the emergence of resistance in vivo is unpredictable and can be evaluated only after prolonged clinical use of the drug.
对肺炎链球菌、粪肠球菌、屎肠球菌以及凝固酶阳性和阴性葡萄球菌的分离株进行了体外研究，以考察它们对LY146032产生耐药性的能力。将这些微生物暴露于递增浓度的LY146032中，结果其最低抑菌浓度（MIC）比原始分离株高出8至32倍。在不含抗生素的培养基上传代三次后，凝固酶阴性葡萄球菌和肺炎球菌仍保持高MIC，粪肠球菌的MIC下降了两倍，金黄色葡萄球菌的MIC下降了四倍。耐药性自发出现的频率在肺炎链球菌中最高（在原始MIC的16倍浓度下为1.2×10⁻⁶），在金黄色葡萄球菌中最低（在原始MIC的8倍浓度下为7.0×10⁻¹⁰）。对于在时间-杀菌研究中存活的细菌，其MIC也高于原始分离株。体外暴露于LY146032会选择出对抗菌剂敏感性降低的菌株。然而，体内耐药性的出现是不可预测的，只有在药物长期临床使用后才能进行评估。
