Clinical and Genomic Epidemiology of mcr-9-Carrying Carbapenem-Resistant Enterobacterales Isolates in Metropolitan Atlanta, 2012 to 2017

• Type of Material: Article
• Authors: Ahmed Babiker, Emory University; Chris Bower, Georgia Emerging Infect Program; Joseph Lutgring, Emory University; Robert A Petit, Theiagen Genomics; Jessica Howard-Anderson, Emory University; Uzma Ansari, Centers for Disease Control and Prevention, Atlanta; Gillian McAllister, Centers for Disease Control and Prevention, Atlanta; Michelle Adamczyk, Centers for Disease Control and Prevention, Atlanta; Erin Breaker, Centers for Disease Control and Prevention, Atlanta; Sarah Satola, Emory University; Jesse Jacob, Emory University; Michael Woodworth, Emory University
• Language: English
• Date: 2022-07-20
• Publisher: AMER SOC MICROBIOLOGY
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Babiker et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1128/spectrum.02522-21
• Title of Journal or Parent Work: MICROBIOLOGY SPECTRUM
• Volume: 10
• Issue: 4
• Start Page: e0252221
• End Page: e0252221
• Keywords: Science & Technology; antimicrobial resistance; MDR; ASSOCIATION; Life Sciences & Biomedicine; healthcare epidemiology; CLOACAE; Microbiology; CRE; multidrug resistance; carbapenem-resistant Enterobacterales; next-generation sequencing; AMR
• Research Categories: Health Sciences, Pathology; Health Sciences, Medicine and Surgery

Abstract

Colistin is a last-resort antibiotic for multidrug-resistant Gram-negative infections. Recently, the ninth allele of the mobile colistin resistance (mcr) gene family, designated mcr-9, was reported. However, its clinical and public health significance remains unclear. We queried genomes of carbapenem-resistant Enterobacterales (CRE) for mcr-9 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 mcr-9-positive and -negative CRE cases were then compared. Among 235 sequenced CRE genomes, 13 (6%) were found to harbor mcr-9, all of which were Enterobacter cloacae complex. The median MIC and rates of heteroresistance and inducible resistance to colistin were similar between mcr-9-positive and -negative isolates. However, rates of resistance were higher among mcr-9-positive isolates across most antibiotic classes. All cases had significant health care exposures. The 90-day mortality was similarly high in both mcr-9-positive (31%) and -negative (7%) CRE cases. Nucleotide identity and phylogenetic analysis did not reveal geotemporal clustering. mcr-9-positive isolates had a significantly higher number of median [range] antimicrobial resistance (AMR) genes (16 [4 to 22] versus 6 [2 to 15]; P, 0.001) than did mcr-9-negative isolates. Pangenome tests confirmed a significant association of mcr-9 detection with mobile genetic element and heavy metal resistance genes. Overall, the presence of mcr-9 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.