In Vitro Activities of ME1036 (CP5609), a Novel Parenteral Carbapenem, against Methicillin-Resistant Staphylococci
In Vitro Activities of ME1036 (CP5609), a Novel Parenteral Carbapenem, against Methicillin-Resistant Staphylococci
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ME1036 (CP5609)（一种新型肠外碳青霉烯类药物）对抗耐甲氧西林葡萄球菌的体外活性
DOI：
10.1128/aac.48.8.2831-2837.2004
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发表时间：
2004
影响因子：
4.9
通讯作者：
M. Yonezawa
中科院分区：
文献类型：
--
作者：
Mizuyo Kurazono;T. Ida;Keiko Yamada;Y. Hirai;Takahisa Maruyama;E. Shitara;M. Yonezawa
摘要ME1036，前身为CP5609，是一种新型的肠外碳青霉烯类药物，其C-2位的碳青霉烯基上直接连接有7-酰基咪唑并[5，1-b]噻唑-2-基。本研究评价了ME1036对临床分离的革兰氏阳性菌和革兰氏阴性菌的体外抗菌活性。ME1036对需氧菌、革兰氏阳性菌和革兰氏阴性菌具有广泛的抗菌活性。与其他上市的β-内酰胺类抗生素不同，ME1036对多重耐药的革兰氏阳性细菌，如甲氧西林耐药葡萄球菌和青霉素耐药肺炎链球菌保持了良好的活性。该化合物对耐甲氧西林金黄色葡萄球菌、耐甲氧西林凝固酶阴性葡萄球菌和耐甲氧西林凝固酶阴性葡萄球菌的MIC值分别为2μg/ml、2μg/ml和0.031μg/ml。在对六种MRSA菌株进行的时间杀伤研究中，ME1036在四倍MIC时导致存活的MRSA细胞数量随时间而减少。ME1036对MRSA的抗菌活性与其对青霉素结合蛋白2a的高亲和力有关，ME1036对青霉素结合蛋白2a的半数抑制浓度约为亚胺培南的300倍。总之，ME1036显示了广泛的抗菌谱和高水平的体外抗葡萄球菌活性，包括对β内酰胺类耐药菌株。
ABSTRACT ME1036, formerly CP5609, is a novel parenteral carbapenem with a 7-acylated imidazo[5,1-b]thiazole-2-yl group directly attached to the carbapenem moiety of the C-2 position. The present study evaluated the in vitro activities of ME1036 against clinical isolates of gram-positive and gram-negative bacteria. ME1036 displayed broad activity against aerobic gram-positive and gram-negative bacteria. Unlike other marketed β-lactam antibiotics, ME1036 maintained excellent activity against multiple-drug-resistant gram-positive bacteria, such as methicillin-resistant staphylococci and penicillin-resistant Streptococcus pneumoniae (PRSP). The MICs of this compound at which 90% of isolates were inhibited were 2 μg/ml for methicillin-resistant Staphylococcus aureus (MRSA), 2 μg/ml for methicillin-resistant coagulase-negative staphylococci, and 0.031 μg/ml for PRSP. In time-kill studies with six strains of MRSA, ME1036 at four times the MIC caused a time-dependent decrease in the numbers of viable MRSA cells. The activity of ME1036 against MRSA is related to its high affinity for penicillin-binding protein 2a, for which the 50% inhibitory concentration of ME1036 was approximately 300-fold lower than that of imipenem. In conclusion, ME1036 demonstrated a broad antibacterial spectrum and high levels of activity in vitro against staphylococci, including β-lactam-resistant strains.