Shakil S, Danishuddin M, Khan A U
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
J Chemother. 2009 Nov;21(5):482-92. doi: 10.1179/joc.2009.21.5.482.
Doripenem is a new 1-beta-methyl carbapenem with broad-spectrum activity against clinically important pathogens. Its activity matches imipenem or ertapenem against Gram-positive bacteria and meropenem against Gram-negative bacteria. It may offer slightly more activity than meropenem against selected pathogens. It does not require the addition of cilastatin. Doripenem is stable to hydrolysis by most of the beta-lactamases, excluding carbapenem-hydrolyzing beta-lactamases. We performed dockings of imipenem, meropenem, ertapenem and doripenem with imipenem-hydrolyzing beta-lactamase, Sme1, separately. Energy calculations revealed that the complex involving doripenem was much less stable. Hence doripenem resists attack by carbapenem-hydrolyzing beta-lactamases at least to some extent. Empiric therapy with doripenem may be useful in hospital settings where multidrug resistance has emerged. However, the proper place for this drug in current antibiotic prescribing practices needs to be determined.
多利培南是一种新型的1-β-甲基碳青霉烯类药物,对临床上重要的病原体具有广谱活性。它对革兰氏阳性菌的活性与亚胺培南或厄他培南相当,对革兰氏阴性菌的活性与美罗培南相当。对某些病原体,它可能比美罗培南的活性略高。它不需要添加西司他丁。多利培南对大多数β-内酰胺酶的水解作用稳定,但不包括碳青霉烯水解β-内酰胺酶。我们分别将亚胺培南、美罗培南、厄他培南和多利培南与亚胺培南水解β-内酰胺酶Sme1进行对接。能量计算表明,涉及多利培南的复合物稳定性要低得多。因此,多利培南至少在一定程度上能抵抗碳青霉烯水解β-内酰胺酶的攻击。在已出现多重耐药性的医院环境中,多利培南经验性治疗可能有用。然而,这种药物在当前抗生素处方实践中的合适位置尚需确定。