Team "Resist" UMR1184 "Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB), INSERM, Paris-Saclay University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-Producing Enterobacteriales, Le Kremlin-Bicêtre, France.
Team "Resist" UMR1184 "Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB), INSERM, Paris-Saclay University, Faculty of Medicine, Le Kremlin-Bicêtre, France; Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-Producing Enterobacteriales, Le Kremlin-Bicêtre, France; Department of Bacteriology-Hygiene, Bicêtre Hospital, Assistance Publique des Hôpitaux de Paris, Le Kremlin-Bicêtre, France.
Clin Microbiol Infect. 2022 Aug;28(8):1156.e1-1156.e5. doi: 10.1016/j.cmi.2022.04.013. Epub 2022 May 6.
Cefiderocol is a catechol-substituted cephalosporin dedicated to the treatment of infections caused by multidrug resistant gram-negative rods. Cefiderocol susceptibility testing might be complex. We compared cefiderocol susceptibility testing methods on a relevant collection of carbapenem-resistant Enterobacterales.
CE-IVD (European CE marking required for all in vitro diagnostic (IVD)) broth microdilution (BMD) plate (ThermoFisher, Waltham, MA, USA) using regular Mueller-Hinton broth, MIC test strip (Liofilchem, Teramo, Italy), and disk diffusion (Liofilchem) were compared to a frozen BMD plate prepared with iron depleted Mueller-Hinton broth. First, a collection of 100 entirely sequenced carbapenem-resistant Enterobacterales was used to compare these methods. Then, a prospective comparison of disk diffusion and CE-IVD BMD was performed on 827 consecutive carbapenem non-susceptible Enterobacterales including 634 carbapenemase-producers.
Compared to reference method, CE-IVD BMD plate gave 95.0% (95% CI, 88.8-97.9) categorisation agreement (CA), 2.8% (95% CI, 0.4-14.2) very major errors (VME), and 1.6% (95% CI, 0.3-8.7) major errors (ME) with high reproducibility. MIC strip gave only 63% (95% CI, 53.2-71.8) of CA and 94.9% (95% CI, 83.1-98.6) of VME due to critical underestimation of the MICs. Disk diffusion gave 77% (95% CI, 67.9-84.2) CA with additional 8% of the isolates within the area of technical uncertainty of 18-22 mm. Prospectively, disk diffusion gave 81.7% (95% CI, 79.0-84.2) CA, 23.3% (95% CI, 15.1-34.2%)VME, and 4.9% (95% CI, 3.6-6.7) ME. Additionally, 21.3% (95% CI, 18.6-24.2) of CRE were within the area of technical uncertainty.
Commercial CE-IVD BMD (ThermoFisher) is accurate for cefiderocol MIC determination in difficult-to-treat Enterobacterales whereas MIC test strip (Liofilchem), that was formulated for Pseudomonas aeruginosa only, should be avoided. Disk diffusion might be useful for screening, but many of these CRE have to be re-tested using BMD to assess definitive categorization.
头孢他啶是一种专门用于治疗多药耐药革兰氏阴性菌引起的感染的儿茶酚取代头孢菌素。头孢他啶药敏试验可能很复杂。我们比较了针对一组相关的耐碳青霉烯肠杆菌科的头孢他啶药敏试验方法。
比较了 CE-IVD（所有体外诊断（IVD）都需要欧盟 CE 标志）肉汤微量稀释（BMD）板（ThermoFisher，马萨诸塞州沃尔瑟姆，美国），使用常规 Mueller-Hinton 肉汤，微量测试条（Liofilchem，意大利泰拉莫）和纸片扩散（Liofilchem）与用缺铁 Mueller-Hinton 肉汤制备的冷冻 BMD 板。首先，使用 100 株完全测序的耐碳青霉烯肠杆菌科来比较这些方法。然后，对 827 株连续的耐碳青霉烯非敏感肠杆菌科进行了前瞻性比较，包括 634 株碳青霉烯酶产生菌，比较了纸片扩散和 CE-IVD BMD。
与参考方法相比，CE-IVD BMD 板的分类一致性（CA）为 95.0%（95%CI，88.8-97.9），非常大误差（VME）为 2.8%（95%CI，0.4-14.2），主要误差（ME）为 1.6%（95%CI，0.3-8.7），具有高重复性。由于 MIC 严重低估，微量测试条仅提供 63%（95%CI，53.2-71.8）的 CA 和 94.9%（95%CI，83.1-98.6）的 VME。纸片扩散法的 CA 为 77%（95%CI，67.9-84.2），另有 8%的分离物处于 18-22mm 的技术不确定区域内。前瞻性地，纸片扩散法的 CA 为 81.7%（95%CI，79.0-84.2），VME 为 23.3%（95%CI，15.1-34.2%），ME 为 4.9%（95%CI，3.6-6.7）。此外，21.3%（95%CI，18.6-24.2）的 CRE 处于技术不确定区域。
用于治疗困难治疗的肠杆菌科的头孢他啶 MIC 测定的商业 CE-IVD BMD（ThermoFisher）是准确的，而仅针对铜绿假单胞菌制定的 MIC 测试条（Liofilchem）应避免使用。纸片扩散法可能对筛选有用，但其中许多 CRE 需要使用 BMD 进行重新测试，以评估明确的分类。
