Galani Irene, Karaiskos Ilias, Souli Maria, Papoutsaki Vassiliki, Gkoufa Aikaterini, Antoniadou Anastasia, Giamarellou Helen
Infectious Diseases Laboratory, 4th Department of Internal Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece.
1st Internal Medicine & Infectious Diseases Department, Hygeia General Hospital, 15123 Athens, Greece.
Antibiotics (Basel). 2025 Feb 21;14(3):223. doi: 10.3390/antibiotics14030223.
The incidence of Ceftazidime/Avibactam (CZA)-resistant isolate co-producing carbapenemase 2 (KPC-2) and Vietnamese extended-spectrum β-lactamase 25 (VEB-25) has been on the rise in Greece over the past five years. This study investigates the isolation of ST323 isolates co-resistant to CZA and cefiderocol (FDC) from colonized and infected patients in a single hospital in Athens. CZA-resistant strains were isolated from 5 ICU patients from 27 December 2023 to 22 January 2024. Antimicrobial susceptibility was tested against a panel of agents. Whole-genome sequencing of the isolates was carried out to identify the acquired resistance genes and mutations that were associated with CZA and FDC resistance. The isolates belonged to ST323 and harbored and . The isolates had a minimum inhibitory concentration (MIC) of >256 mg/L for CZA and 32 mg/L for FDC, due to the disrupted catecholate siderophore receptor Fiu. was located on an IncC non-conjugative plasmid and on a ~14 kb multidrug resistance (MDR) region comprising 15 further acquired resistance genes. Transformation studies showed that the -carrying plasmid provided resistance to most of the β-lactams tested, including CZA. The isolates remained susceptible to carbapenems, imipenem/relebactam, and meropenem/vaborbactam. The plasmid harbored the citrate-dependent iron (III) uptake system (), which increased the MIC of FDC from ≤0.08 mg/L to 2 mg/L. The gene was associated with IncC plasmids which are important contributors to the spread of key antibiotic resistance genes. Strict infection control measures must be elaborated upon to prevent the spread of extensively drug-resistant organisms such as those described here.
在过去五年中，希腊对头孢他啶/阿维巴坦（CZA）耐药且同时产碳青霉烯酶2（KPC - 2）和越南超广谱β-内酰胺酶25（VEB - 25）的分离株的发生率一直在上升。本研究调查了在雅典一家医院中，从定植和感染患者中分离出的对CZA和头孢地尔（FDC）均耐药的ST323分离株。2023年12月27日至2024年1月22日期间，从5名重症监护病房患者中分离出了对CZA耐药的菌株。对一组抗菌药物进行了药敏试验。对分离株进行全基因组测序，以鉴定与CZA和FDC耐药相关的获得性耐药基因和突变。这些分离株属于ST323，携带了[此处原文缺失具体基因信息]和[此处原文缺失具体基因信息]。由于儿茶酚盐铁载体受体Fiu被破坏，这些分离株对CZA的最低抑菌浓度（MIC）>256 mg/L，对FDC的MIC为32 mg/L。[此处原文缺失具体基因信息]位于IncC非接合质粒和一个约14 kb的多药耐药（MDR）区域上，该区域还包含另外15个获得性耐药基因。转化研究表明，携带[此处原文缺失具体基因信息]的质粒对包括CZA在内的大多数测试β-内酰胺类药物具有耐药性。这些分离株对碳青霉烯类、亚胺培南/瑞来巴坦和美罗培南/万巴巴坦仍敏感。该质粒携带了柠檬酸盐依赖性铁（III）摄取系统（[此处原文缺失具体基因信息]），它将FDC的MIC从≤0.08 mg/L提高到了2 mg/L。[此处原文缺失具体基因信息]基因与IncC质粒相关，IncC质粒是关键抗生素耐药基因传播的重要因素。必须制定严格的感染控制措施，以防止此类广泛耐药生物体的传播。
