Mouton Johan W, Vinks Alexander A
Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
Curr Opin Crit Care. 2007 Oct;13(5):598-606. doi: 10.1097/MCC.0b013e3282e2a98f.
Continuous infusion of beta-lactam antibiotics is becoming increasingly popular. The background and current clinical evidence are discussed. Tools to apply continuous infusion are analyzed.
One randomized controlled trial in an ICU setting and two nonrandomized controlled trials have shown continuous infusion to be more beneficial than intermittent infusion. One randomized controlled trial in chronic obstructive pulmonary disorder patients, however, showed no difference between the two treatments. The stability of most beta-lactams for use during continuous infusion has been documented.
Killing of bacteria by beta-lactam antibiotics is maximal at around four times the minimum inhibitory concentration in vitro. To ensure an optimal effect when treating severe infections, free unbound concentrations at or above four times the minimum inhibitory concentration should be maintained. Although continuous infusion has been demonstrated to be superior in animal studies, randomized clinical trials have failed to confirm this in humans, primarily because of suboptimal design. A better designed randomized clinical trial, set up as a pilot study, recently demonstrated a favorable outcome with continuous infusion. A major issue during continuous infusion is the stability of the antibiotic, which may limit its application. The calculation of the infusion rate necessary to obtain the desired free drug concentration is relatively straightforward.
β-内酰胺类抗生素持续输注正变得越来越普遍。本文将讨论其背景及当前临床证据,并分析应用持续输注的工具。
一项在重症监护病房环境下进行的随机对照试验以及两项非随机对照试验表明,持续输注比间歇输注更有益。然而,一项针对慢性阻塞性肺疾病患者的随机对照试验显示,两种治疗方法之间没有差异。大多数β-内酰胺类抗生素在持续输注期间的稳定性已有文献记载。
β-内酰胺类抗生素在体外达到约四倍最低抑菌浓度时对细菌的杀灭作用最强。为确保在治疗严重感染时达到最佳效果,应维持游离未结合浓度在四倍最低抑菌浓度或以上。尽管在动物研究中已证明持续输注更具优势,但随机临床试验未能在人体中证实这一点,主要原因是设计欠佳。一项设计更好的随机临床试验作为初步研究,最近显示持续输注有良好结果。持续输注期间的一个主要问题是抗生素的稳定性,这可能会限制其应用。计算获得所需游离药物浓度所需的输注速率相对简单。