Department of Biomedical and Biotechnological Sciences, Università di Catania, Via Santa Sofia 97, I-95123 Catania, Italy.
Shionogi Srl, Rome, Italy.
J Glob Antimicrob Resist. 2021 Jun;25:390-398. doi: 10.1016/j.jgar.2021.04.019. Epub 2021 May 18.
Antimicrobial resistance, particularly carbapenem resistance, in Gram-negative pathogens poses a significant healthcare threat. Carbapenem resistance rates in Italy are among the highest in Europe. We report the in vitro activity of cefiderocol, a novel siderophore cephalosporin, and comparator antibiotics against Gram-negative isolates from Italy as part of the SIDERO-WT studies.
Isolates were collected between 2014 and 2018. Minimum inhibitory concentrations (MICs) were determined using International Organization for Standardization and EUCAST guidelines. Antimicrobial susceptibilities were interpreted using EUCAST breakpoints; pharmacodynamic/pharmacokinetic breakpoints were used if EUCAST breakpoints were not specified.
The 2472 isolates [1545 (62.5%) Enterobacterales and 927 (37.5%) non-fermenters] represented a range of infection sources, including nosocomial pneumonia (902; 36.5%), complicated urinary tract infection (374; 15.1%), bloodstream infection (596; 24.1%), complicated intra-abdominal infection (257; 10.4%) and other infection sources (343; 13.9%). Cefiderocol was active against the majority of isolates, regardless of infection source (susceptibility, 94.2-97.3%). A high proportion of non-fermenters (97.6%) and Enterobacterales (95.6%) were cefiderocol-susceptible, although susceptibility was lower in Klebsiella pneumoniae (88.1%). Susceptibility to cefiderocol was significantly (P < 0.01) greater than comparators overall (96.4% vs. 71.3-81.6%) and in non-fermenters (97.6% vs. 44.3-90.3%) across infection sources. Overall 612/2472 isolates (24.8%) were meropenem-resistant (MIC > 8 mg/L), comprising 516/927 (55.7%) non-fermenters and 96/1545 (6.2%) Enterobacterales. Cefiderocol (499/516; 96.7%) activity was greater than colistin (440/516; 85.3%), ceftazidime/avibactam (123/516; 23.8%) and ceftolozane/tazobactam (89/516; 17.2%) in meropenem-resistant non-fermenter isolates.
Susceptibility to cefiderocol was significantly greater than meropenem, colistin, ceftazidime/avibactam and ceftolozane/tazobactam overall, regardless of infection source.
革兰氏阴性病原体的抗生素耐药性，尤其是碳青霉烯类耐药性，对医疗保健构成重大威胁。意大利的碳青霉烯类耐药率在欧洲属于最高之列。我们报告了新型铁载体头孢菌素头孢地尔的体外活性，以及作为 SIDERO-WT 研究一部分的比较抗生素对来自意大利的革兰氏阴性分离株的活性。
分离株于 2014 年至 2018 年期间采集。使用国际标准化组织和欧盟药敏试验委员会指南确定最小抑菌浓度（MIC）。使用欧盟药敏试验委员会的折点来解释抗菌药物敏感性；如果欧盟药敏试验委员会没有指定，则使用药效学/药代动力学折点。
2472 株分离株[1545 株（62.5%）肠杆菌科和 927 株（37.5%）非发酵菌]代表了一系列感染源，包括医院获得性肺炎（902 株；36.5%）、复杂性尿路感染（374 株；15.1%）、血流感染（596 株；24.1%）、复杂性腹腔内感染（257 株；10.4%）和其他感染源（343 株；13.9%）。头孢地尔对大多数分离株均具有活性，无论感染源如何（敏感性，94.2-97.3%）。大多数非发酵菌（97.6%）和肠杆菌科（95.6%）对头孢地尔敏感，尽管肺炎克雷伯菌的敏感性较低（88.1%）。头孢地尔的敏感性总体显著高于比较药物（96.4% vs. 71.3-81.6%），在非发酵菌中也显著高于比较药物（97.6% vs. 44.3-90.3%），无论感染源如何。2472 株分离株中共有 612 株（24.8%）为美罗培南耐药（MIC>8mg/L），其中 516 株（55.7%）为非发酵菌，96 株（6.2%）为肠杆菌科。头孢地尔（499/516；96.7%）的活性大于多粘菌素（440/516；85.3%）、头孢他啶/阿维巴坦（123/516；23.8%）和头孢洛扎/他唑巴坦（89/516；17.2%）在美罗培南耐药非发酵菌分离株中。
无论感染源如何，头孢地尔的敏感性均显著高于美罗培南、多粘菌素、头孢他啶/阿维巴坦和头孢洛扎/他唑巴坦。
