Multidrug-resistant Gram-negative bacteria: how to treat and for how long
Multidrug-resistant Gram-negative bacteria: how to treat and for how long
复制标题
DOI：
10.1016/j.ijantimicag.2010.11.014
复制
发表时间：
2010-12-01
影响因子：
10.8
通讯作者：
Giamarellou, Helen
中科院分区：
文献类型：
--
作者：
Giamarellou, Helen
多重耐药(MDR)革兰氏阴性杆菌的出现给医院感染的治疗带来了很大的问题。随着药物供应的减少，唯一的治疗选择是两种复苏的抗菌药(粘菌素和磷霉素)，一种较新的(替格环素)和一种早期的新糖苷(ACHN-490)。多粘菌素自1947年被发现以来，主要以多粘菌素E(Colistin)为代表，最近在治疗最难治疗的耐多药革兰氏阴性病原菌-铜绿假单胞菌、鲍曼不动杆菌和肺炎克雷伯菌方面获得了主要地位。然而，尽管在59-75%的病例中取得了有希望的治疗结果，但已报道的研究有共同的缺点，即缺乏对照组，其回顾性质，治疗的剂量和持续时间可变，70%的病例同时使用其他抗生素，以及缺乏耐药性发展监测。因此，设计良好的前瞻性临床试验的必要性迫在眉睫。磷霉素在体外对耐多药的肠杆菌科细菌具有活性，包括高比例的铜绿假单胞菌；然而，在治疗多药耐药感染的肠外制剂和防止耐药性发展的最佳组合方面缺乏临床经验。替格环素对耐多药的肠杆菌科细菌和鲍曼不动杆菌有较强的抗药性，临床应用效果良好。然而，由于血液水平较低，需要调整剂量。ACHN-490具有良好的体外抗多药耐药肺炎克雷伯菌活性，目前仍处于尿路感染的早期II期试验。同时，严格执行感染控制措施是预防医院感染的基石，不应忽视抗生素管理，例如适当的疗程和降级政策。(C)2010年Elsevier B.V.和国际化疗学会。版权所有。
The emergence of multidrug-resistant (MDR) Gram-negative bacilli creates a big problem for the treatment of nosocomial infections. As the pharmaceutical pipeline wanes, the only therapeutic options are two revived antibacterials (colistin and fosfomycin), a newer one (tigecycline) and an early-phase neoglycoside (ACHN-490). Polymyxins, known since 1947, are mostly represented by polymyxin E (colistin), which has recently gained a principal position in the management of the most difficult-to-treat MDR Gram-negative pathogens - Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. However, despite promising therapeutic results in 59-75% of cases, the reported studies share common drawbacks, i.e. the absence of a control group, their retrospective nature, variable dosing and duration of therapy, simultaneous administration of other antibiotics in >70% and a lack of resistance development monitoring. The necessity for well-designed prospective clinical trials is therefore urgent. Fosfomycin is active in vitro against MDR Enterobacteriaceae, including a high proportion of P. aeruginosa; however, clinical experience is lacking with the parenteral formulation in MDR infection and on the best combinations to prevent resistance development. Tigecycline, which is active against MDR Enterobacteriaceae and A. baumannii, has shown satisfactory clinical experience. However, dosage adjustment is required because of low blood levels. ACHN-490, which has promising in vitro activity against MDR K. pneumoniae, is still in early phase II trials in urinary tract infections. Meanwhile, the strict application of infection control measures is the cornerstone of nosocomial infection prevention, and antibiotic stewardship, exemplified by appropriate duration of therapy and de-escalation policies, should not be overlooked. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.