Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic approaches.
Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic approaches.
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DOI：
10.1517/14656566.2014.914172
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发表时间：
2014-07
影响因子：
3.2
通讯作者：
Giamarellou H
中科院分区：
文献类型：
--
作者：
Karaiskos I;Giamarellou H
简介：在多重耐药、广泛耐药（XDR）甚至泛耐药革兰氏阴性微生物的时代，医学界正面临无法治疗的感染的威胁，特别是由产碳青霉烯酶的细菌，即肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌引起的感染。因此，所有目前可用的抗生素，以及为不久的将来的化合物，提出和讨论。 涵盖的领域：目前的知识有关的作用机制，体外活性和相互作用，药代动力学/药效学，临床疗效和毒性问题的复苏和新的抗菌药物克服目前的耐药机制，包括粘菌素，替加环素，磷霉素，替莫西林，碳青霉烯类，抗生素仍在开发中，为不久的将来，如普拉佐霉素，eravacycline和碳青霉烯酶抑制剂进行了讨论。 专家意见：粘菌素在体外和体内对重症宿主中产XDR碳青霉烯酶的微生物具有活性，而替加环素（铜绿假单胞菌除外）具有相似的活性谱。目的观察联合用药治疗肺炎克雷伯菌感染和呼吸机相关性肺炎的疗效。肺炎克雷伯氏菌产碳青霉烯酶似乎是强制性的，而在铜绿假单胞菌和A.鲍曼不动杆菌它的疗效值得怀疑。磷霉素对铜绿假单胞菌和克雷伯菌有活性。肺炎，虽然有前途，但在XDR感染方面经验不足。新的有效化合物的体内有效性仍然需要III期临床试验的评估，特别是在XDR感染中。
Introduction: In the era of multidrug-resistant, extensively drug-resistant (XDR) and even pandrug-resistant Gram-negative microorganisms, the medical community is facing the threat of untreatable infections particularly those caused by carbapenemase-producing bacteria, that is, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. Therefore, all the presently available antibiotics, as well as for the near future compounds, are presented and discussed. Areas covered: Current knowledge concerning mechanisms of action, in vitro activity and interactions, pharmacokinetic/pharmacodynamics, clinical efficacy and toxicity issues for revived and novel antimicrobial agents overcoming current resistance mechanisms, including colistin, tigecycline, fosfomycin, temocillin, carbapenems, and antibiotics still under development for the near future such as plazomicin, eravacycline and carbapenemase inhibitors is discussed. Expert opinion: Colistin is active in vitro and effective in vivo against XDR carbapenemase-producing microorganisms in the critically ill host, whereas tigecycline, with the exception of P. aeruginosa, has a similar spectrum of activity. The efficacy of combination therapy in bacteremias and ventilator-associated pneumonia caused by K. pneumoniae carbapenemase producers seems to be obligatory, whereas in cases of P. aeruginosa and A. baumannii its efficacy is questionable. Fosfomycin, which is active against P. aeruginosa and K. pneumoniae, although promising, shares poor experience in XDR infections. The in vivo validity of the newer potent compounds still necessitates the evaluation of Phase III clinical trials particularly in XDR infections.