Response to Giufre et al

To the Editor—We thank Guifre et al for sharing their interesting data regarding the clonal distribution of Escherichia coli clinical isolates from their locale in relation to resistance phenotype, and we support their call for more such studies [1]. Their findings agree closely with ours regarding the predominance, since at least 2006, of sequence type (ST) 131 and, specifically, its H30 subclone, among fluoroquinolone-resistant (FQ-R) E. coli isolates, as compared to ST131's quite low prevalence among fluoroquinolone-susceptible (FQ-S) E. coli isolates [2]. A novel observation by Giufre et al pertains to the relative prevalence of the H30 ST131 subclone, compared with that of other ST131 subclones (mainly, H22), within the minor ST131 subset among FQ-S isolates. Specifically, Guifre et al found that the H30 subclone accounted for 13 (72%) of their 18 total FQ-S ST131 isolates from 2006, 2009, and 2012 combined [1]. In contrast, we have consistently found that the H30 subclone's contribution to the FQ-S subset within ST131 is relatively small (<25%), including in our initial convenience sample study [2], a subsequent nationwide systematic survey of E. coli isolates from US veterans in 2011 [3], and a recent population-based survey from Olmsted County, Minnesota [4]. Although these differences could simply reflect study design differences, they also may indicate true geographical differences in the prevalence of FQ-S H30 subclone isolates. The relative prominence of FQ-S H31 isolates observed by Giufre et al suggests that factors other than just the FQ-R phenotype, such as high metabolic potential [5] or enhanced virulence, may partially explain, at least in some locales, the H30 subclone's dramatic success over the past decade. We agree strongly with Giufre et al that FQ resistance likely emerged within the H30 ST131 subclone on a single occasion, in a FQ-S H30 progenitor, via a specific combination of mutations in gyrA and parC, followed by the explosive expansion of the new FQ-R H30 subset [1]. Elucidation of the basis for the H30 ST131 subclone's dramatic expansion after it acquired FQ resistance should provide critical insights into what allows an E. coli clone to “go viral,” which could lead to the development of sorely needed preventive interventions. Giufre et al have contributed additional evidence implicating the ST131 H30 subclone as the currently most successful strain of extraintestinal pathogenic E. coli. Because of its clinical predominance and multidrug resistance, the H30 lineage conceivably has as great a social and economic impact as that of any lineage of methicillin-resistant Staphylococcus aureus.