French G L
Department of Infection, King's College and Guy's and St Thomas Hospital, London, UK.
Clin Microbiol Infect. 2008 Dec;14 Suppl 6:19-29. doi: 10.1111/j.1469-0691.2008.02124.x.
Despite increasing antimicrobial resistance and multiple drug resistance in clinical isolates of both Gram-positive and Gram-negative bacteria, there are few novel antimicrobial agents in development. The few new agents that have been recently licensed have tended to have narrow spectra of activity, focused on Gram-positive pathogens, especially methicillin-resistant Staphylococcus aureus (MRSA). This situation is rightly causing concern among clinicians and public health authorities worldwide. This article reviews available data on three new antibacterials currently in development. The cephalosporin ceftobiprole is active against MRSA, Enterococcus faecalis and penicillin-resistant Streptococcus pneumoniae, but otherwise has a spectrum of activity similar to that of other recent cephalosporins. In a clinical trial, ceftobiprole was non-inferior to vancomycin for the treatment of MRSA-associated complicated skin and skin structure infections (cSSSIs). Doripenem, a new carbapenem, has some activity against MRSA, but otherwise has an anti-Gram-positive spectrum of activity similar to that of imipenem and an anti-Gram-negative spectrum similar to that of meropenem. In a clinical trial, it was non-inferior to meropenem for the treatment of complicated intra-abdominal infections. Iclaprim is a dihydrofolate reductase inhibitor with greatly enhanced activity, as compared with trimethoprim, against a range of Gram-positive and Gram-negative pathogens. The limited literature concerning this agent has concentrated on its potential role in the treatment of infections with Gram-positive bacteria. A clinical trial has demonstrated the non-inferiority of iclaprim, as compared with linezolid, in the treatment of cSSSIs, including those associated with MRSA.
尽管革兰氏阳性菌和革兰氏阴性菌的临床分离株中抗菌药物耐药性和多重耐药性不断增加，但目前正在研发的新型抗菌药物却很少。最近获批的几种新型药物往往活性谱较窄，主要针对革兰氏阳性病原体，尤其是耐甲氧西林金黄色葡萄球菌（MRSA）。这种情况理所当然地引起了全球临床医生和公共卫生当局的关注。本文综述了目前正在研发的三种新型抗菌药物的现有数据。头孢比普对MRSA、粪肠球菌和耐青霉素肺炎链球菌具有活性，但在其他方面其活性谱与其他近期头孢菌素相似。在一项临床试验中，头孢比普在治疗与MRSA相关的复杂性皮肤和皮肤结构感染（cSSSIs）方面不劣于万古霉素。多利培南是一种新型碳青霉烯类药物，对MRSA有一定活性，但在其他方面其抗革兰氏阳性菌活性谱与亚胺培南相似，抗革兰氏阴性菌活性谱与美罗培南相似。在一项临床试验中，它在治疗复杂性腹腔内感染方面不劣于美罗培南。依克拉普明是一种二氢叶酸还原酶抑制剂，与甲氧苄啶相比，对一系列革兰氏阳性和革兰氏阴性病原体的活性大大增强。关于这种药物的有限文献主要集中在其在治疗革兰氏阳性菌感染中的潜在作用。一项临床试验表明，依克拉普明在治疗cSSSIs（包括与MRSA相关的感染）方面与利奈唑胺相比不劣。
