Epidemic Emergence in the United States of Escherichia coli Sequence Type 131- H 30 (ST131- H 30), 2000 to 2009

Abstract

The H30 subclone of Escherichia coli sequence type 131 (ST131-H30) has become the leading antimicrobial resistance E. coli lineage in the United States and often exhibits resistance to one or both of the two key antimicrobial classes for treating Gram-negative infections, extended-spectrum cephalosporins (ESCs) and fluoroquinolones (FQs). However, the timing of and reasons for its recent emergence are inadequately defined. Accordingly, from E. coli clinical isolates collected systematically across the United States by the SENTRY Antimicrobial Surveillance Program in 2000, 2003, 2006, and 2009, 234 isolates were selected randomly, stratified by year, within three resistance categories: (i) ESCreduced susceptibility, regardless of FQ phenotype (ESC-RS); (ii) FQ resistance, ESC susceptible (FQ-R); and (iii) FQ susceptible, ESC susceptible (FQ-S). Susceptibility profiles, phylogroup, ST, ST131 subclone, and virulence genotypes were determined, and temporal trends and between-variable associations were assessed statistically. From 2000 to 2006, concurrently with the emergence of ESC-RS and FQ-R strains, the prevalence of (virulence-associated) phylogroup B2 among such strains also rose dramatically, due entirely to rapid emergence of ST131, especially H30. By 2009, H30 was the dominant E. coli lineage overall (22%), accounting for a median of 43% of all single-agent and multidrug resistance (68% for ciprofloxacin). H30's emergence increased the net virulence gene content of resistant (especially FQ-R) isolates, giving stable overall virulence gene scores despite an approximately 4-fold expansion of the historically less virulent resistant population. These findings define more precisely the timing and tempo of H30's emergence in the United States, identify possible reasons for it, and suggest potential consequences, including more frequent and/or aggressive antimicrobialresistant infections.

Rapid Emergence, Subsidence, and Molecular Detection of Escherichia coli Sequence Type 1193- fimH64 , a New Disseminated Multidrug-Resistant Commensal and Extraintestinal Pathogen

“…Fifth, our novel ST1193-H64 PCR-based assay was simple and accurate and so should facilitate the molecular epidemiological studies needed to further assess the prevalence, ecology, and clinical significance of ST1193-H64. Regarding clonal emergence, several recent reports have documented ST1193-H64 as an emerging contributor to the FQ-R E. coli population (7)(8)(9)(10)(11)(12)(13), usually second only to ST131-H30, which in contrast emerged globally beginning nearly 2 decades ago (6,24,(36)(37)(38)(39)(40). Our findings suggest a staggered timing for the emergence of ST1193-H64 at different centers, with historical isolates from Australia dating to 2008; a low prevalence in 2011 in Olmsted County, MN, and at VAMCs nationally in the United States; and a later appearance at MVAMC (2013), followed by a rapid rise and then a plateau and even a possible decline (fecal colonization).…”

“…Molecular typing. Established multiplex PCR-based assays were used to identify E. coli phylogroups (22), nine clonal subsets (including STc14) within group B2 (23), ST131 and its H30R subclone (5), 50 E. coli virulence genes (24), and the O75 and O18 antigen-encoding rfb regions (25). Clonal typing was done for all FQ-R isolates (clinical and fecal), all FQ-S isolates from the University of Minnesota and Olmsted County, a random 25% subsample of non-ST131 group B2 FQ-S MVAMC clinical isolates through April 2017 and all such isolates thereafter, and selected FQ-S MVAMC fecal surveillance isolates.…”

Antimicrobial Activity Evaluation of Tebipenem (SPR859), an Orally Available Carbapenem, against a Global Set of Enterobacteriaceae Isolates, Including a Challenge Set of Organisms

“…Increasing rates of cephalosporin resistance have been reported among these pathogens and a main reason is because of the dissemination of ESBLs, particularly CTX-M-15 and CTX-M-14, depending on the geographic region (5,12). Another important contributor to the rising rates of antimicrobial resistance is the dissemination of E. coli ST131, particularly the H30Rx subset, which often displays resistance to broad-spectrum cephalosporins and fluoroquinolones (7,8). A previous study reported an occurrence of 45% of ST131 among E. coli isolates in 2009 in the United States (7).…”

“…The spread of a specific E. coli clone that is defined by phylogenetic group B2, serotype O25:H4, and multilocus sequence typing (MLST) 131 has also been identified as an important contributor to the epidemic of antimicrobial resistance in hospital and community settings, especially for first-line agents, such as fluoroquinolones and broad-spectrum cephalosporins (7)(8)(9). This epidemiologic shift has great implications for the empirical management of community-associated UTIs; therefore, oral agents to treat outpatients at high risk for infections caused by ESBL-producing pathogens or inpatients who could benefit from step-down therapy would become valuable assets in the antimicrobial armamentarium.…”

Epidemiology and antimicrobial resistance characteristics of the ST131-H30subclone among extraintestinalEscherichia colicollected from US children

“…[2][3][4][5] Molecular epidemiologic studies have shown that a subclone of ST131, termed H30, has driven the global dissemination of ST131. [6][7][8][9] The clonal structure of ST131-H30 is tightly linked to antimicrobial resistance; the vast majority of H30 isolates are fluoroquinolone resistant due to mutations in the gyrA and parC chromosomal genes (isolates known as H30-R or clade C), while nested subclones are additionally associated with the production of CTX-M-type extended-spectrum beta-lactamases (ESBLs) that confer resistance to extended-spectrum cephalosporins ( Figure S1). [7,8,[10][11][12] Although E. coli ST131-H30 (hereafter, H30) has been recognized as a clone of significant public health importance, [5,13] there is a lack of data about its epidemiology in children.…”