University College London Hospitals NHS Foundation Trust, London, UK.
University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
J Glob Antimicrob Resist. 2021 Dec;27:1-11. doi: 10.1016/j.jgar.2021.07.014. Epub 2021 Jul 27.
The prevalence of Gram-negative bacteria (GNB) demonstrating extensive, multiple antimicrobial resistance is increasing in England, leaving few treatment choices. Cefiderocol is a novel siderophore cephalosporin approved in Europe for the treatment of aerobic GNB infections in adults with limited treatment options. We report pooled data for a clinical isolate set collected in England between 2014-2018.
MICs were determined by broth microdilution according to International Organization for Standardization guidelines. Cefiderocol susceptibility was tested using iron-depleted cation-adjusted Muller-Hinton broth. Susceptibility rates were based on EUCAST breakpoints. In the absence of a species-specific breakpoint, pharmacokinetic/pharmacodynamic breakpoints were used.
Of 1886 isolates from England [74.1% Enterobacterales (18.7% Escherichia coli, 17.2% Klebsiella pneumoniae), 25.9% non-fermenters (18.4% Pseudomonas aeruginosa, 3.7% Acinetobacter baumannii)], 98.7% were cefiderocol-susceptible. Cefiderocol susceptibility in Enterobacterales (99.0%) was significantly (P < 0.01) greater than ceftolozane/tazobactam (94.3%), but similar to meropenem (99.3%) and ceftazidime/avibactam (99.4%). Overall, cefiderocol susceptibility (98.0%) in non-fermenters was significantly (P < 0.01) higher than comparators (range, 84.5-92.4%). Susceptibility to cefiderocol was 98.3-99.6% by infection source and was significantly (P < 0.01) greater than comparators for isolates from patients with nosocomial pneumonia (cefiderocol, 98.3%; comparators range, 79.8-93.8%). Excluding intrinsically meropenem-resistant Stenotrophomonas maltophilia, 47/1846 isolates (2.5%) were meropenem-resistant. A high proportion of meropenem-resistant P. aeruginosa were susceptible to cefiderocol (95.0%). All S. maltophilia isolates (40/40) were cefiderocol-susceptible.
A substantial proportion of clinical isolates from England, representing a wide range of pathogens across multiple infection sources, was cefiderocol-susceptible. Cefiderocol retained activity against meropenem-resistant strains.
在英国，表现出广泛、多重抗微生物耐药性的革兰氏阴性菌（GNB）的流行率正在上升，治疗选择有限。头孢他啶是一种新型的铁载体头孢菌素，在欧洲被批准用于治疗有有限治疗选择的成人需氧 GNB 感染。我们报告了在 2014 年至 2018 年期间在英国收集的临床分离物集的汇总数据。
根据国际标准化组织指南，通过肉汤微量稀释法测定 MIC。使用缺铁阳离子调整的 Muller-Hinton 肉汤测试头孢他啶的敏感性。根据 EUCAST 折点确定敏感性率。在没有特定物种折点的情况下，使用药代动力学/药效学折点。
来自英国的 1886 株分离株[74.1%肠杆菌科（18.7%大肠埃希菌，17.2%肺炎克雷伯菌），25.9%非发酵菌（18.4%铜绿假单胞菌，3.7%鲍曼不动杆菌）]，98.7%对头孢他啶敏感。肠杆菌科中头孢他啶的敏感性（99.0%）显著（P<0.01）大于头孢他啶/他唑巴坦（94.3%），但与美罗培南（99.3%）和头孢他啶/阿维巴坦（99.4%）相似。总体而言，非发酵菌中头孢他啶的敏感性（98.0%）显著（P<0.01）高于对照药物（范围为 84.5-92.4%）。根据感染源，头孢他啶对分离株的敏感性为 98.3-99.6%，显著（P<0.01）高于耐碳青霉烯类铜绿假单胞菌（头孢他啶，98.3%；对照药物范围为 79.8-93.8%）。排除固有耐美罗培南的嗜麦芽窄食单胞菌，1846 株分离株中有 47 株（2.5%）为耐美罗培南。耐美罗培南铜绿假单胞菌中有很大比例对头孢他啶敏感（95.0%）。所有嗜麦芽窄食单胞菌分离株（40/40）均对头孢他啶敏感。
来自英国的大量临床分离株，代表了多种感染源的广泛病原体，对头孢他啶敏感。头孢他啶对耐美罗培南菌株仍具有活性。
