Fosfomycin has been shown to have a wide spectrum of activity against multidrug-resistant Gram-negative bacteria; however, breakpoints have been established only for Escherichia coli or Enterobacterales per the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST), respectively. A lack of additional organism breakpoints limits clinical use of this agent and has prompted extrapolation of these interpretive categories to other organisms like Pseudomonas aeruginosa without supporting evidence. Further complicating the utility of fosfomycin is the specified method for MIC determination, namely, agar dilution, which is not widely available and is both labor and time intensive. We therefore sought to determine the susceptibility of a large international collection of P. aeruginosa isolates (n = 198) to fosfomycin and to compare testing agreement rates across four methods: agar dilution, broth microdilution, disk diffusion, and Etest. Results were interpreted according to CLSI E. coli breakpoints, with 49.0 to 85.8% considered susceptible, dependent upon the testing method used. Epidemiological cutoff values were calculated and determined to be 256 μg/ml and 512 μg/ml for agar dilution and broth microdilution, respectively. Agreement rates were analyzed using both agar dilution and broth microdilution with a resulting high essential agreement rate of 91.3% between the two susceptibility testing methods. These results indicate that broth microdilution may be a reliable method for fosfomycin susceptibility testing against P. aeruginosa and stress the need for P. aeruginosa-specific breakpoints.

中文翻译：

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针对国际临床铜绿假单胞菌分离物的四种磷霉素药敏试验方法的性能。

磷霉素已经显示出对多种耐药革兰氏阴性细菌具有广泛的活性。但是，分别根据临床和实验室标准协会（CLSI）和欧洲抗菌药物敏感性测试委员会（EUCAST）为大肠杆菌或肠杆菌建立了断点。缺乏额外的生物断点限制了该药物的临床使用，并促使将这些解释性类别外推至其他生物，如铜绿假单胞菌没有证据。磷霉素的实用性进一步复杂化的是用于测定MIC的特定方法，即琼脂稀释法，这种方法尚不广泛，而且劳动和时间都很繁琐。因此，我们寻求确定国际上大量的铜绿假单胞菌分离物（n = 198）对磷霉素的敏感性，并比较四种方法的测试一致性：琼脂稀释，肉汤微稀释，圆盘扩散和Etest。根据CLSI E. coli解释结果取决于所使用的测试方法，断点的敏感度为49.0％至85.8％。计算出的琼脂稀释度和肉汤微量稀释度的流行病学临界值分别为256μg/ ml和512μg/ ml。使用琼脂稀释液和肉汤微量稀释液分析一致率，两种药敏试验方法之间的基本一致率为91.3％。这些结果表明肉汤微量稀释可能是针对磷铜绿假单胞菌的磷霉素药敏试验的可靠方法，并强调了对铜绿假单胞菌特异的断点的需求。