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替莫西林重获生机。

Temocillin revived.

作者信息

Livermore David M, Tulkens Paul M

机构信息

Antibiotic Resistance Monitoring and Reference Laboratory, Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, UK.

出版信息

J Antimicrob Chemother. 2009 Feb;63(2):243-5. doi: 10.1093/jac/dkn511. Epub 2008 Dec 18.

Abstract

Resistance in Gram-negative pathogens is an increasing concern, with carbapenems often appearing as the only acceptable treatment option in serious infections. Reviving older compounds that have fallen into disuse may help to alleviate this burden. Temocillin (6-alpha-methoxy-ticarcillin) is resistant to most if not all classical and extended-spectrum beta-lactamases and to AmpC enzymes. It is also chemically stable, allowing administration by continuous infusion. Pharmacokinetic/pharmacodynamic analysis, aided by Monte-Carlo simulations, suggests a breakpoint of 8 mg/L for the registered maximum dosage of 4 g daily. Temocillin's weaknesses, explaining its limited previous use, are a lack of activity against Gram-positive organisms, anaerobes and Pseudomonas. In settings where these are unlikely or are covered by other agents, temocillin may be useful, potentially 'sparing' carbapenems and having little apparent potential to select for Clostridium difficile.

摘要

革兰氏阴性病原体的耐药性问题日益受到关注,在严重感染中,碳青霉烯类药物常常成为唯一可接受的治疗选择。重新启用已被弃用的旧化合物可能有助于减轻这一负担。替莫西林(6-α-甲氧基替卡西林)对大多数(即便不是全部)经典和超广谱β-内酰胺酶以及AmpC酶具有耐药性。它在化学性质上也很稳定,可通过持续输注给药。借助蒙特卡洛模拟进行的药代动力学/药效学分析表明,对于每日4克的注册最大剂量,其折点为8毫克/升。替莫西林的弱点,也就是其此前使用受限的原因,在于它对革兰氏阳性菌、厌氧菌和铜绿假单胞菌缺乏活性。在这些细菌不太可能出现或者可由其他药物覆盖的情况下,替莫西林可能会有用,有可能“节省”碳青霉烯类药物,并且几乎没有明显的选择艰难梭菌的可能性。

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