Global Incidence of Carbapenemase-Producing Escherichia coli ST131

We characterized Escherichia coli ST131 isolates among 116 carbapenemase-producing strains. Of isolates from 16 countries collected during 2008–2013, 35% belonged to ST131 and were associated with blaKPC, H30 lineage, and virotype C. This study documents worldwide incidents of resistance to “last resort” antimicrobial drugs among a common pathogen in a successful sequence type.

E scherichia coli sequence type 131 (ST131) was iden- tified as pathogenic to humans in 2008; retrospective research suggests that its isolates have been present since at least 2003.The group has spread extensively and has been linked to the rapid global increase in the prevalence of antimicrobial resistance among E. coli strains (1).The intercontinental dissemination of this sequence type has contributed immensely to the worldwide emergence of fluoroquinolone-resistant and CTX-M-producing E. coli (1,2).Recent surveillance studies have shown that its overall prevalence ranges from 12.5% to 30% of all E. coli clinical isolates, from 70% to 80% of fluoroquinolone-resistant isolates, and from 50% to 60% of extended spectrum betalactamase-producing isolates (3).
The development of resistance to carbapenems among E. coli is of particular concern because these agents are often the last line of effective therapy available for the treatment of persons with serious infections (4).New Delhi metallo-β-lactamase (NDM) and carbapenem-hydrolyzing oxacillinase-48 (OXA-48) are the most common carbapenemases among E. coli worldwide (5).
PCR testing for O25b:H4, O16:H5, and MLST showed that 41/116 (35%) belonged to the sequence type ST131.Antimicrobial susceptibilities, types of β-lactamases, the presence of the fimH30 lineage, and virotypes are shown in Table 1.ST131strains were more likely than non-ST131 strains to be nonsusceptible to ciprofloxacin and to be positive for bla KPC , the H30 lineage, and virotype C; non-ST131 isolates were more likely to be positive for bla NDM .

Conclusions
NDM variants were the most common carbapenemase identified and were especially prevalent in E. coli strains from India and Vietnam (Table 2).KPCs, which were the second most common carbapenemase identified, were distributed globally, i.e., in South America, Central America, North America, Europe, the Middle East, and Asia (Table 2).This was unexpected because KPCs have been relatively rarely reported among E. coli (5).
Because of the unprecedented global success of ST131, the presence of carbapenemases had been carefully monitored by molecular epidemiologists but has been limited to case reports from several countries (1).The largest collections of ST131 with carbapenemases were reported from Hangzhou, Zhejiang Province, China (13) and Pittsburgh, Pennsylvania, USA (14).Of note, 24/38 (63%) of E. coli strains with bla KPC belonged to ST131, as opposed to 3/44 (7%) for NDMs and 13/30 (43%) for OXA-48-like strains.Our results suggest that ST131 is most likely responsible for the global distribution of E. coli with bla KPC .
The expansion of the H30 lineage and its H30-R and H30-Rx sublineages have contributed substantially to the spread of ST131 E. coli (11,15).In our study, H30-R, which belongs to virotype C, was the most common lineage among ST131 strains (i.e., 58%); it was associated with bla KPC and was especially prominent during 2012-2013.
The increase of the ST131 H30 lineage with bla KPC during 2012-13 is cause for concern.
E. coli ST131 has received comparatively less attention than other antimicrobial-resistant pathogens.Retrospective molecular surveillance studies have shown that ST131 with bla CTX-M-15 was rare during the early 2000s, but that an explosive global increase followed during the midto-late 2000s (1).The results of this study show a similar scenario with E. coli ST131 and bla KPC ; a low prevalence combined with a global distribution.This study is of special concern because we documented resistance to "last resort" antimicrobial drugs (i.e., carbapenems) in most regions of the world, in a common community and hospital pathogen (i.e., E. coli) among a very successful sequence type (i.e., ST131).We urgently need well-designed epidemiologic and molecular studies to clarify the dynamics of transmission, risk factors, and reservoirs for ST131.
The medical community can ill afford to ignore E. coli ST131strains with carbapenemases.This sequence type poses a major threat to public health because of its worldwide distribution and association with the dominant H30 lineage.This sequence type among E. coli has the potential to cause widespread resistance to carbapenems.
This work was supported by a research grant from the Calgary Laboratory Services (#10006465).J.D.D.P. had previously received research funds from Merck and Astra Zeneca.PAB is an employee of Astra Zeneca.K.M.K., R.E.B., M.H. and D.J.H. are employees of International Health Management Associates, which is under contract by Merck and AstraZeneca.
coli strains collected globally by 2 research groups during 2008-2013.