Poulakou Garyphallia, Giamarellou Helen
University General Hospital ATTIKON, National and Kapodistrian University, Athens Medical School, 124 62 Athens, Greece.
Expert Opin Investig Drugs. 2008 May;17(5):749-71. doi: 10.1517/13543784.17.5.749.
Potent new drugs against multidrug-resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter spp. and pan-drug-resistant Klebsiella pneumoniae, which constitute an increasing medical threat, are almost absent from the future pharmaceutical pipeline.
This drug evaluation focuses on the position of doripenem, a novel forthcoming carbapenem. Mechanisms of resistance and new drugs with anti-Gram-negative activity are also briefly reviewed.
Literature search was performed for new carbapenems, new antibiotics, doripenem, metallo-beta-lactamase inhibitors, multidrug-resistant pathogens, antipseudomonal antibiotics and multidrug-resistant epidemiology.
Doripenem possesses a broad spectrum of activity against Gram-negative bacteria, similar to that of meropenem, while retaining the spectrum of imipenem against Gram-positive pathogens. Against P. aeruginosa, doripenem exhibits rapid bactericidal activity with 2 - 4-fold lower MIC values, compared to meropenem. Exploitation of pharmacokinetic/pharmacodynamic applications could offer a treatment opportunity against strains exhibiting borderline resistance to doripenem. Stability against numerous beta-lactamases, low adverse event potential and more potent in vitro antibacterial activity against P. aeruginosa and A. baumanni compared to the existing carbapenems, are its principal features.
针对多重耐药革兰氏阴性菌，即铜绿假单胞菌、不动杆菌属以及构成日益严重医学威胁的泛耐药肺炎克雷伯菌的强效新药，在未来的制药产品线中几乎不存在。
本药物评估聚焦于即将推出的新型碳青霉烯类药物多立培南的地位。还简要回顾了耐药机制及具有抗革兰氏阴性菌活性的新药。
对新型碳青霉烯类药物、新型抗生素、多立培南、金属β-内酰胺酶抑制剂、多重耐药病原体、抗铜绿假单胞菌抗生素及多重耐药流行病学进行文献检索。
多立培南对革兰氏阴性菌具有广谱活性，与美罗培南相似，同时保留了亚胺培南对革兰氏阳性病原体的抗菌谱。与美罗培南相比，多立培南对铜绿假单胞菌表现出快速杀菌活性，其最低抑菌浓度（MIC）值低2至4倍。利用药代动力学/药效学应用可为对多立培南表现出临界耐药的菌株提供治疗机会。与现有碳青霉烯类药物相比，对多种β-内酰胺酶稳定、不良事件潜在风险低以及对铜绿假单胞菌和鲍曼不动杆菌具有更强的体外抗菌活性，是其主要特点。
