Division of Infectious Diseases, Department of Medicine, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA.
Department of Pathology and Laboratory Medicine, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA.
Microbiol Spectr. 2022 Aug 31;10(4):e0252221. doi: 10.1128/spectrum.02522-21. Epub 2022 Jul 20.
Colistin is a last-resort antibiotic for multidrug-resistant Gram-negative infections. Recently, the ninth allele of the mobile colistin resistance () gene family, designated was reported. However, its clinical and public health significance remains unclear. We queried genomes of carbapenem-resistant (CRE) for from a convenience sample of clinical isolates collected between 2012 and 2017 through the Georgia Emerging Infections Program, a population- and laboratory-based surveillance program. Isolates underwent phenotypic characterization and whole-genome sequencing. Phenotypic characteristics, genomic features, and clinical outcomes of -positive and -negative CRE cases were then compared. Among 235 sequenced CRE genomes, 13 (6%) were found to harbor , all of which were Enterobacter cloacae complex. The median MIC and rates of heteroresistance and inducible resistance to colistin were similar between -positive and -negative isolates. However, rates of resistance were higher among -positive isolates across most antibiotic classes. All cases had significant health care exposures. The 90-day mortality was similarly high in both -positive (31%) and -negative (7%) CRE cases. Nucleotide identity and phylogenetic analysis did not reveal geotemporal clustering. -positive isolates had a significantly higher number of median [range] antimicrobial resistance (AMR) genes (16 [4 to 22] versus 6 [2 to 15]; < 0.001) than did -negative isolates. Pangenome tests confirmed a significant association of detection with mobile genetic element and heavy metal resistance genes. Overall, the presence of was not associated with significant changes in colistin resistance or clinical outcomes, but continued genomic surveillance to monitor for emergence of AMR genes is warranted. Colistin is a last-resort antibiotic for multidrug-resistant Gram-negative infections. A recently described allele of the mobile colistin resistance () gene family, designated has been widely reported among species. However, its clinical and public health significance remains unclear. We compared characteristics and outcomes of -positive and -negative CRE cases. All cases were acquired in the health care setting and associated with a high rate of mortality. The presence of was not associated with significant changes in colistin resistance, heteroresistance, or inducible resistance but was associated with resistance to other antimicrobials and antimicrobial resistance (AMR), virulence, and heavy metal resistance (HMR) genes. Overall, the presence of was not associated with significant phenotypic changes or clinical outcomes. However, given the increase in AMR and HMR gene content and potential clinical impact, continued genomic surveillance of multidrug-resistant organisms to monitor for emergence of AMR genes is warranted.
多黏菌素是治疗多重耐药革兰氏阴性感染的最后手段。最近,报道了移动多黏菌素耐药基因家族的第九个等位基因,命名为 。然而,其临床和公共卫生意义仍不清楚。我们通过佐治亚州新兴感染计划(一个基于人群和实验室的监测计划),从 2012 年至 2017 年期间收集的临床分离株中,对耐碳青霉烯肠杆菌科(CRE)进行了移动多黏菌素耐药基因家族的基因 检测。分离株进行了表型特征和全基因组测序。然后比较了 阳性和 阴性 CRE 病例的临床特征、基因组特征和临床结局。在 235 个测序的 CRE 基因组中,发现 13 个(6%)携带 ,均为阴沟肠杆菌复合体。阳性和阴性分离株的多黏菌素 MIC 值和异质性耐药及诱导耐药率相似。然而,在大多数抗生素类别中, 阳性分离株的耐药率更高。所有病例均有显著的医疗保健暴露史。90 天死亡率在 阳性(31%)和 阴性(7%)CRE 病例中相似。核苷酸同一性和系统发育分析未显示地理时间聚类。与 阴性分离株相比, 阳性分离株的中位 [范围] 抗生素耐药(AMR)基因数量显著增加(16 [4 至 22] 与 6 [2 至 15];< 0.001)。泛基因组检测证实了检测到的 与移动遗传元件和重金属耐药基因的显著关联。总体而言, 存在与否与多黏菌素耐药或临床结局无显著相关性,但需要继续进行基因组监测以监测 AMR 基因的出现。
多黏菌素是治疗多重耐药革兰氏阴性感染的最后手段。最近描述的一种移动多黏菌素耐药基因家族的等位基因,命名为 ,在 种中广泛报道。然而,其临床和公共卫生意义仍不清楚。我们比较了 阳性和 阴性 CRE 病例的特征和结局。所有病例均在医疗机构获得,与高死亡率相关。多黏菌素耐药基因的存在与多黏菌素耐药、异质性耐药或诱导性耐药无显著相关性,但与其他抗菌药物和抗菌药物耐药(AMR)、毒力和重金属耐药(HMR)基因相关。总体而言, 存在与否与表型变化或临床结局无显著相关性。然而,鉴于 AMR 和 HMR 基因含量的增加以及潜在的临床影响,需要继续对多药耐药生物体进行基因组监测,以监测 AMR 基因的出现。