SUMMARY: Escherichia coli sequence type 131 (ST131) and Klebsiella pneumoniae ST258 emerged in the 2000s as important human pathogens, have spread extensively throughout the world, and are responsible for the rapid increase in antimicrobial resistance among E. coli and K. pneumoniae strains, respectively. E. coli ST131 causes extraintestinal infections and is often fluoroquinolone resistant and associated with extended-spectrum β-lactamase production, especially CTX-M-15. K. pneumoniae ST258 causes urinary and respiratory tract infections and is associated with carbapenemases, most often KPC-2 and KPC-3. The most prevalent lineage within ST131 is named fimH30 because it contains the H30 variant of the type 1 fimbrial adhesin gene, and recent molecular studies have demonstrated that this lineage emerged in the early 2000s and was then followed by the rapid expansion of its sublineages H30-R and H30-Rx. K. pneumoniae ST258 comprises 2 distinct lineages, namely clade I and clade II. Moreover, it seems that ST258 is a hybrid clone that was created by a large recombination event between ST11 and ST442. Epidemic plasmids with bla _CTX-M and bla _KPC belonging to incompatibility group F have contributed significantly to the success of these clones. E. coli ST131 and K. pneumoniae ST258 are the quintessential examples of international multidrug-resistant high-risk clones.

The management of infections due to Klebsiella pneumoniae has been complicated by the emergence of antimicrobial resistance, especially to carbapenems. Resistance to carbapenems in K. pneumoniae involves multiple mechanisms, including the production of carbapenemases (e.g., KPC, NDM, VIM, OXA-48-like), as well as alterations in outer membrane permeability mediated by the loss of porins and the upregulation of efflux systems. The latter two mechanisms are often combined with high levels of other types of β-lactamases (e.g., AmpC). K. pneumoniae sequence type 258 (ST258) emerged during the early to mid-2000s as an important human pathogen and has spread extensively throughout the world. ST258 comprises two distinct lineages, namely, clades I and II, and it seems that ST258 is a hybrid clone that was created by a large recombination event between ST11 and ST442. Incompatibility group F plasmids with bla _KPC have contributed significantly to the success of ST258. The optimal treatment of infections due to carbapenemase-producing K. pneumoniae remains unknown. Some newer agents show promise for treating infections due to KPC producers; however, effective options for the treatment of NDM producers remain elusive.

Enterobacteriaceae, especially Klebsiella spp. producing extended-spectrum β-lactamases (ESBLs) such as SHV and TEM types, have been established since the 1980s as a major cause of hospital-acquired infections. Appropriate infection control practices have largely prevented the dissemination of these bacteria within many hospitals, although outbreaks have been reported. However, during the late 1990s and 2000s, Enterobacteriaceae (mostly Escherichia coli) producing novel ESBLs, the CTX-M enzymes, have been identified predominantly from the community as a cause of urinary tract infections. Resistance to other classes of antibiotics, especially the fluoroquinolones, is often associated with ESBL-producing organisms. Many clinical laboratories are still not aware of the importance of screening for ESBL-producing Enterobacteriaceae originating from the community. A heightened awareness of these organisms by clinicians and enhanced testing by laboratories, including molecular surveillance studies, is required to reduce treatment failures, to limit their introduction into hospitals and to prevent the spread of these emerging pathogens within the community.

Surveillance studies have shown that OXA-48-like carbapenemases are the most common carbapenemases in Enterobacterales in certain regions of the world and are being introduced on a regular basis into regions of nonendemicity, where they are responsible for nosocomial outbreaks. OXA-48, OXA-181, OXA-232, OXA-204, OXA-162, and OXA-244, in that order, are the most common enzymes identified among the OXA-48-like carbapenemase group.

There is an enormous global public health burden due to antimicrobial resistance (AMR) Klebsiella pneumoniae high-risk clones. K. pneumoniae ST307 and ST147 are recent additions to the family of successful clones among these species. Both clones likely emerged in Europe during the early to mid-1990s, and in a relatively short time, became prominent global pathogens, spreading to all continents (with the exception of Antarctica). ST307 and ST147 consist of multiple clades/clusters respectively and are associated with various carbapenemases (i.e. KPCs, NDMs, OXA-48-like and VIMs). ST307 is endemic in Italy, Colombia, USA (Texas), and South Africa, while ST147 is endemic in India, Italy, Greece and certain North African countries. Both clones have been introduced into non-endemic regions leading to world-wide nosocomial outbreaks. Genomic studies showed ST307 and ST147 contain identical gyrA and parC mutations and likely obtained plasmids with bla_CTX-M-15 during the early to mid-2000s, which aided in their global distribution. ST307 and ST147 then acquired plasmids with various carbapenemases during the late 2000s, establishing themselves as important AMR pathogens in certain regions. Both clones are likely underreported due to restricted detection methodologies. ST307 and ST147 have the ability to become major threats to public health due to their worldwide distribution, ability to cause serious infections and association with AMR including pan-resistance. The medical community at large, especially those concerned with antimicrobial resistance, should be aware of the looming threat posed by emerging AMR high-risk clones such as K. pneumoniae ST307 and ST147.