Jiang Jianping, Komarow Lauren, Hill Carol, Boutzoukas Angelique E, Hanson Blake, Arias Cesar A, Bonomo Robert A, Evans Scott, Doi Yohei, Satlin Michael J, Weston Gregory, Cober Eric, Valderrama-Beltran Sandra Liliana, Mendoza Soraya Salcedo, Liu Zhengyin, Fries Bettina C, Tambyah Paul Ananth, Chambers Henry F, Fowler Vance G, van Duin David, Kreiswirth Barry N, Chen Liang
Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey.
The Biostatistics Center, George Washington University, Rockville, Maryland.
J Infect Dis. 2025 Jul 11;231(6):1489-1501. doi: 10.1093/infdis/jiae616.
Despite the global public health threat posed by carbapenem-resistant Enterobacter spp, clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp infections.
Hospitalized patients enrolled in the CRACKLE-2 study (ClinicalTrials.gov, NCT03646227) from 2016 to 2018 with cultures positive for carbapenemase-producing Enterobacter spp were included. Clinical and microbiologic data were collected from health records. Whole genome sequencing was performed, and the population structures of selected predominant clones were analyzed.
We enrolled 136 hospitalized patients with carbapenemase-producing Enterobacter spp from 30 hospitals in 7 countries. Among the 136 isolates, 11 Enterobacter spp were identified, with most isolates belonging to E xiangfangensis (n = 81 [60%]) and E hoffmannii (n = 17 [13%]) and carrying blaKPC (n = 106 [78%]) and blaNDM (n = 12 [9%]). Clinical characteristics and outcomes were similar among patients with E xiangfangensis, E hoffmannii, or the other Enterobacter spp. Thirty-day mortality was 20%, and older age at enrollment (adjusted odds ratio, 1.42 [95% confidence interval, 1.08-1.87]) was associated with increased mortality. Sequence type (ST) 171 E xiangfangensis, ST78 E hoffmannii, and ST93 E xiangfangensis were the predominant clones, and the acquisition of fluoroquinolone resistance-associated mutations and carbapenemase-encoding plasmids contributed to their formation and global dissemination.
Our findings demonstrate that E xiangfangensis and E hoffmannii are common species among international carbapenemase-producing Enterobacter spp, potentially linked to the clonal spread of a few predominant clones that have acquired fluoroquinolone resistance and carbapenemase-encoding plasmids.
尽管耐碳青霉烯类肠杆菌属细菌对全球公共卫生构成威胁，但关于国际分离株的临床和分子流行病学研究仍然匮乏。从历史上看，肠杆菌属的分类一直具有挑战性，这限制了我们对产碳青霉烯酶肠杆菌属细菌感染的临床特征和结局的理解。
纳入2016年至2018年参加CRACKLE-2研究（ClinicalTrials.gov，NCT03646227）且培养出产碳青霉烯酶肠杆菌属细菌阳性的住院患者。从健康记录中收集临床和微生物学数据。进行全基因组测序，并分析选定主要克隆的群体结构。
我们纳入了来自7个国家30家医院收治的136例产碳青霉烯酶肠杆菌属细菌感染的住院患者。在136株分离株中，鉴定出11种肠杆菌属细菌，大多数分离株属于湘芳肠杆菌（n = 81 [60%]）和霍氏肠杆菌（n = 17 [13%]），并携带blaKPC（n = 106 [78%]）和blaNDM（n = 12 [9%]）。湘芳肠杆菌、霍氏肠杆菌或其他肠杆菌属细菌感染患者的临床特征和结局相似。30天死亡率为20%，入院时年龄较大（调整优势比为1.42 [95%置信区间为1.08 - 1.87]）与死亡率增加相关。序列类型（ST）171的湘芳肠杆菌、ST78的霍氏肠杆菌和ST93的湘芳肠杆菌是主要克隆，获得氟喹诺酮耐药相关突变和碳青霉烯酶编码质粒促进了它们的形成和全球传播。
我们的数据表明，湘芳肠杆菌和霍氏肠杆菌是国际上产碳青霉烯酶肠杆菌属细菌中的常见菌种，可能与少数获得氟喹诺酮耐药性和碳青霉烯酶编码质粒的主要克隆的克隆传播有关。
