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Volume 20, Number 11—November 2014
Dispatch

Global Incidence of Carbapenemase-Producing Escherichia coli ST131

Gisele Peirano, Patricia Bradford, Krystyna M. Kazmierczak, Robert E. Badal, Meredith Hackel, Daryl J. Hoban, and Johann D.D. PitoutComments to Author 
Author affiliations: University of Calgary Faculty of Medicine, Calgary, Alberta, Canada (G. Peirano, J.D.D. Pitout); AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA (P.A. Bradford); International Health Management Associates, Schaumburg, Illinois, USA (K.M. Kazmierczak, R.E. Badal, M. Hackel, D.J. Hoban)

Cite This Article

Abstract

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.

Escherichia coli sequence type 131 (ST131) was identified 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 beta-lactamase-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).

The Study

This study describes the characteristics of ST131 isolates among carbapenemase-producing E. coli strains collected globally by 2 research groups during 2008–2013. The Merck Study for Monitoring Antimicrobial Resistance Trends (SMART) (http://www.merck.com/about/featured-stories/infectious_disease.html) started in 2002 and AstraZeneca's global surveillance study of antimicrobial resistance (unpublished data) began in 2012, to monitor global antimicrobial resistance trends among gram-negative bacteria (Technical Appendix). Antimicrobial susceptibilities of different antimicrobial agents (Table 1) were determined by using frozen broth microdilution panels according to 2013 Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing guidelines (6). Established PCR and sequencing methods were used to identify β-lactamase genes (7,8) and define O25b:H4, O16:H5 ST131, fimH30 lineage, H30-Rx sublineage (911), and virotypes (12).

Overall, 47,843 E. coli isolates were collected and tested for susceptibility; 407 were found to be nonsusceptible to ertapenem or imipenem and were molecularly characterized for β-lactamase genes. A total of 116 of the 407 isolates were positive for NDM, KPC, OXA-48-like, VIM, and IMP types of carbapenemases. Various gene types were identified: 44 (38%) were positive for blaNDM, 38 (33%) for blaKPC, 30 (26%) for blaOXA-48-like, 2 (2%) for blaVIM-1 and 2 (2%) were positive for blaIMP (Table 1).

The countries from which the E. coli isolates were obtained are shown in Table 2. The isolates were cultured from intraabdominal specimens (37%), peritoneal fluid (16%), biliary fluid (10%), urine (30%), and from miscellaneous sources such as sputum and tissue (9%).

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 blaKPC, the H30 lineage, and virotype C; non-ST131 isolates were more likely to be positive for blaNDM.

The majority, i.e., 24 (58%), of ST131strains were positive for blaKPC, 13 (32%) for blaOXA-48-like, 3 (7%) for blaNDM-1, and 1 (2%) for blaIMP-14. ST131 was present in 16 countries spanning 5 continents (Table 2). The distribution of ST131 during 2008–2013 is shown in Table 3.

Various fimH alleles were identified among ST131 isolates: 24 H30 (58%), 3 H41 (7%), 3 H54 (7%), 2 H22 (5%), 2 H27 (5%), and 2 H191 (5%); and 1 each (2%) belonging to H24, H32, H65, and the new fimH alleles H434 and H435. Of the 24 H30 ST131 strains, 19 (79%) belonged to the H30-R sublineage and 5(21%) to the H30-Rx sublineage.

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 blaKPC 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 blaKPC.

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 blaKPC and was especially prominent during 2012–2013. The increase of the ST131 H30 lineage with blaKPC 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 blaCTX-M-15 was rare during the early 2000s, but that an explosive global increase followed during the mid-to-late 2000s (1). The results of this study show a similar scenario with E. coli ST131 and blaKPC; 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.

Dr Peirano is a research associate at Calgary Laboratory Services and the University of Calgary. Her main research interests are related to the detection and molecular epidemiology of antimicrobial drug resistance mechanisms among Gram-negative bacteria.

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Acknowledgments

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.

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References

  1. Nicolas-Chanoine  MH, Bertrand  X, Madec  JY. Escherichia coli ST131, an intriguing clonal group. Clin Microbiol Rev. 2014;27:54374. DOIPubMed
  2. Peirano  G, Pitout  JD. Molecular epidemiology of Escherichia coli producing CTX-M β-lactamases: the worldwide emergence of clone ST131 O25:H4. Int J Antimicrob Agents. 2010;35:31621. DOIPubMed
  3. Banerjee  R, Johnson  JR. A new clone sweeps clean: the enigmatic emergence of Escherichia coli sequence type 131. Antimicrob Agents Chemother. 2014;58:49975004. DOIPubMed
  4. Pitout  JD. Extraintestinal pathogenic Escherichia coli: an update on antimicrobial resistance, laboratory diagnosis and treatment. Expert Rev Anti Infect Ther. 2012;10:116576. DOIPubMed
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  8. Lascols  C, Hackel  M, Marshall  SH, Hujer  AM, Bouchillon  S, Badal  R, Increasing prevalence and dissemination of NDM-1 metallo-β-lactamase in India: data from the SMART study (2009). J Antimicrob Chemother. 2011;66:19927. DOIPubMed
  9. Banerjee  R, Robicsek  A, Kuskowski  MA, Porter  S, Johnston  BD, Sokurenko  E, Molecular epidemiology of Escherichia coli sequence type 131 and Its H30 and H30-Rx subclones among extended-spectrum-β-lactamase-positive and -negative E. coli clinical isolates from the Chicago Region, 2007 to 2010. Antimicrob Agents Chemother. 2013;57:63858. DOIPubMed
  10. Johnson  JR, Clermont  O, Johnston  B, Clabots  C, Tchesnokova  V, Sokurenko  E, Rapid and specific detection, molecular epidemiology, and experimental virulence of the O16 subgroup within Escherichia coli sequence type 131. J Clin Microbiol. 2014;52:135865. DOIPubMed
  11. Johnson  JR, Tchesnokova  V, Johnston  B, Clabots  C, Roberts  PL, Billig  M, Abrupt emergence of a single dominant multidrug-resistant strain of Escherichia coli. J Infect Dis. 2013;207:91928. DOIPubMed
  12. Blanco  J, Mora  A, Mamani  R, Lopez  C, Blanco  M, Dahbi  G, Four main virotypes among extended-spectrum-β-lactamase-producing isolates of Escherichia coli O25b:H4–B2-ST131: bacterial, epidemiological, and clinical characteristics. J Clin Microbiol. 2013;51:335867. DOIPubMed
  13. Cai  JC, Zhang  R, Hu  YY, Zhou  HW, Chen  GX. Emergence of Escherichia coli sequence type 131 isolates producing KPC-2 carbapenemase in China. Antimicrob Agents Chemother. 2014;58:114652. DOIPubMed
  14. O'Hara  JA, Hu  F, Ahn  C, Nelson  J, Rivera  JI, Pasculle  AW, Molecular epidemiology of KPC-producing Escherichia coli: occurrence of ST131-fimH30 subclone harboring pKpQIL-like IncFIIk plasmid. Antimicrob Agents Chemother. 2014;58:42347 . DOIPubMed
  15. Price  LB, Johnson  JR, Aziz  M, Clabots  C, Johnston  B, Tchesnokova  V, The epidemic of extended-spectrum-beta-lactamase–producing Escherichia coli ST131 is driven by a single highly pathogenic subclone, H30-Rx. MBio. 2013;4:e0037713. DOIPubMed

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Tables

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Cite This Article

DOI: 10.3201/eid2011.141388

CrossRef reports the first page should be "e00377-13" not "e00377" in reference 15 "Price, Johnson, Aziz, Clabots, Johnston, Tchesnokova, et al., 2013".

Please verify the page numbers (e00377-13) (in reference 15 "Price, Johnson, Aziz, Clabots, Johnston, Tchesnokova, et al., 2013").

PRODUCTION NOTE: This table is online only.

Table of Contents – Volume 20, Number 11—November 2014

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Johan D.D. Pitout, University of Calgary, Calgary Laboratory Services, #9, 3535 Research Rd NW, Calgary, Alberta, Canada

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Page created: October 17, 2014
Page updated: October 17, 2014
Page reviewed: October 17, 2014
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
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