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Rapidly spreading Enterobacterales with OXA-48-like carbapenemases
Gisele Peirano1,2, Johann D D Pitout1,2,3,4
1Division of Microbiology, Alberta Precision Laboratories, Calgary, Alberta, Canada.
Abstract:
Enterobacterales (mostly Klebsiella pneumoniae, Escherichia coli) with OXA-48-like carbapenemases (e.g., OXA-48, -181, -232, -244) are undermining the global efficiency of carbapenem therapy. In the Middle East, North Africa, and some European countries, OXA-48-like carbapenemases are the most common types of carbapenemases among Enterobacterales. Currently, OXA-48 is endemic in the Middle East, North Africa, Spain, France, and Belgium; OXA-181 is endemic in Sub-Saharan Africa and the Indian Subcontinent, while OXA-232 has been increasing in the Indian Subcontinent. European countries (e.g., Germany, Denmark, Switzerland, France) are experiencing community outbreaks with E. coli ST38 that produce OXA-244, and these strains have been introduced into Norwegian, Polish, and Czech hospitals. The global ascendancy of OXA-48-like genes is due to the combination of carbapenemases with horizontal spread through promiscuous plasmids (e.g., IncL, IncX3, ColE2) and vertical spread with certain high-risk multidrug-resistant clones (e.g., K. pneumoniae ST14, ST15, ST147, ST307; E. coli ST38, ST410). This is a powerful "gene survival strategy" that has assisted with the survival of OXA-48-like genes in different environments including the community setting. The laboratory diagnosis is complex; therefore, bacteria with "difficult to detect" variants (e.g., OXA-244, OXA-484) are likely underreported and are spreading silently "beneath the radar" in hospital and community settings. K. pneumoniae and E. coli with OXA-48-like carbapenemases are forces to be reckoned with.
Insights
OXA-48-like carbapenemases in Enterobacterales, particularly Klebsiella pneumoniae and Escherichia coli, are a growing global threat. These carbapenem-resistant bacteria spread via plasmids and clones, complicating treatment and diagnosis.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- OXA-48-like carbapenemases are a significant threat to carbapenem therapy effectiveness.
- These carbapenemases are prevalent in Enterobacterales, especially Klebsiella pneumoniae and Escherichia coli, in the Middle East, North Africa, and parts of Europe.
- Specific variants like OXA-48, OXA-181, OXA-232, and OXA-244 show distinct geographical endemicity and increasing prevalence.
Purpose of the Study:
- To highlight the global spread and impact of OXA-48-like carbapenemases in Enterobacterales.
- To explain the mechanisms contributing to the ascendancy of these resistance genes.
- To underscore the challenges in laboratory diagnosis and the silent spread of these resistant bacteria.
Main Methods:
- Review of epidemiological data on the prevalence and geographical distribution of OXA-48-like carbapenemases.
- Analysis of genetic mechanisms, including horizontal gene transfer via plasmids and vertical spread through bacterial clones.
- Discussion of diagnostic complexities associated with certain OXA variants.
Main Results:
- OXA-48-like carbapenemases are the most common carbapenemases among Enterobacterales in MENA and some European countries.
- Specific clones of Klebsiella pneumoniae and Escherichia coli carrying these genes are spreading globally.
- Difficult-to-detect variants like OXA-244 and OXA-484 contribute to underreporting and silent dissemination.
Conclusions:
- OXA-48-like carbapenemases in Klebsiella pneumoniae and Escherichia coli pose a significant and escalating global health challenge.
- The combination of plasmid-mediated horizontal spread and clonal vertical transmission facilitates the widespread dissemination of these resistance genes.
- The complexity of laboratory detection necessitates enhanced surveillance to curb the silent spread in both hospital and community settings.
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