Livermore David M, Andrews Jenny M, Hawkey Peter M, Ho Pak-Leung, Keness Yoram, Doi Yohei, Paterson David, Woodford Neil
Norwich Medical School, University of East Anglia, Norwich, UK.
J Antimicrob Chemother. 2012 Jul;67(7):1569-77. doi: 10.1093/jac/dks088. Epub 2012 Mar 29.
Recent EUCAST advice asserts that, with low breakpoints, susceptibility results for cephalosporins and carbapenems can be reported 'as found', even for strains with extended-spectrum β-lactamases (ESBLs) and carbapenemases. The CLSI has similar advice, but with higher ceftazidime and cefepime breakpoints than those of EUCAST. Pharmacodynamic and animal data are used to support these views, along with some analysis of clinical case series. We contend that such advice is misguided on three counts. First, whilst there are cases on record where cephalosporins and carbapenems have proved effective against infections due to low-MIC ESBL producers and low-MIC carbapenemase producers, respectively, there are similar numbers of cases where such therapy has failed. Second, routine susceptibility testing is less precise than in research analyses, meaning that ESBL and carbapenemase producers with 'real' MICs of 1-8 mg/L will oscillate between susceptibility categories according to who tests them and how. Third, although EUCAST continues to advocate ESBL and carbapenemase detection for epidemiological purposes, the likely consequence of not seeking these enzymes for treatment purposes is that some laboratories will not seek them at all, leading to a loss of critical infection control information. In short, it is prudent to continue to seek ESBLs and carbapenemases directly and, where they are found, generally to avoid substrate drugs as therapy.
欧盟CAST近期的建议称，对于头孢菌素和碳青霉烯类药物，采用低折点时，即使是对产超广谱β-内酰胺酶（ESBLs）和碳青霉烯酶的菌株，药敏结果也可“按实际情况报告”。美国临床和实验室标准协会（CLSI）有类似建议，但头孢他啶和头孢吡肟的折点高于欧盟CAST。药效学和动物实验数据以及一些临床病例系列分析被用于支持这些观点。我们认为该建议在三个方面存在误导。第一，虽然有记录表明头孢菌素和碳青霉烯类药物分别对低MIC的产ESBLs菌株和低MIC的产碳青霉烯酶菌株所致感染有效，但也有同样数量的病例显示这种治疗失败。第二，常规药敏试验不如研究分析精确，这意味着“实际”MIC为1 - 8mg/L的产ESBLs和产碳青霉烯酶菌株会因检测者和检测方式的不同而在药敏类别之间波动。第三，虽然欧盟CAST继续倡导出于流行病学目的检测ESBLs和碳青霉烯酶，但不针对治疗目的检测这些酶的可能后果是一些实验室根本不会去检测，从而导致关键的感染控制信息丢失。简而言之，继续直接检测ESBLs和碳青霉烯酶，并在发现这些酶时通常避免使用底物药物进行治疗是谨慎之举。
