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The Global Ascendency of OXA-48-Type Carbapenemases
Johann D D Pitout1,2,3,4, Gisele Peirano5,2, Marleen M Kock4,6
1Division of Microbiology, Alberta Public Laboratories, Edmonton, Alberta, Canada jpitout@ucalgary.ca.
Abstract:
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. OXA-48 is associated with different Tn1999 variants on IncL plasmids and is endemic in North Africa and the Middle East. OXA-162 and OXA-244 are derivatives of OXA-48 and are present in Europe. OXA-181 and OXA-232 are associated with ISEcp1, Tn2013 on ColE2, and IncX3 types of plasmids and are endemic in the Indian subcontinent (e.g., India, Bangladesh, Pakistan, and Sri Lanka) and certain sub-Saharan African countries. Overall, clonal dissemination plays a minor role in the spread of OXA-48-like carbapenemases, but certain high-risk clones (e.g., Klebsiella pneumoniae sequence type 147 [ST147], ST307, ST15, and ST14 and Escherichia coli ST38 and ST410) have been associated with the global dispersion of OXA-48, OXA-181, OXA-232, and OXA-204. Chromosomal integration of blaOXA-48 within Tn6237 occurred among E. coli ST38 isolates, especially in the United Kingdom. The detection of Enterobacterales with OXA-48-like enzymes using phenotypic methods has improved recently but remains challenging for clinical laboratories in regions of nonendemicity. Identification of the specific type of OXA-48-like enzyme requires sequencing of the corresponding genes. Bacteria (especially K. pneumoniae and E. coli) with blaOXA-48, blaOXA-181, and blaOXA-232 are emerging in different parts of the world and are most likely underreported due to problems with the laboratory detection of these enzymes. The medical community should be aware of the looming threat that is posed by bacteria with OXA-48-like carbapenemases.
Insights
OXA-48-like carbapenemases are a growing threat in Enterobacterales, causing hospital outbreaks worldwide. Early detection and awareness are crucial to combat the spread of these challenging antibiotic-resistant bacteria.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- OXA-48-like carbapenemases are prevalent in Enterobacterales in specific global regions.
- These enzymes are increasingly detected in non-endemic areas, leading to nosocomial outbreaks.
- Common OXA-48-like enzymes include OXA-48, OXA-181, OXA-232, OXA-204, OXA-162, and OXA-244.
Purpose of the Study:
- To review the epidemiology and global spread of OXA-48-like carbapenemases.
- To highlight the challenges in detecting these enzymes in clinical laboratories.
- To raise awareness about the threat posed by carbapenemase-producing Enterobacterales.
Main Methods:
- Review of surveillance data on carbapenemase prevalence.
- Analysis of geographical distribution and associated mobile genetic elements.
- Discussion of clonal dissemination patterns and high-risk clones.
- Assessment of diagnostic challenges for OXA-48-like enzymes.
Main Results:
- OXA-48 is endemic in North Africa/Middle East, OXA-162/OXA-244 in Europe, and OXA-181/OXA-232 in the Indian subcontinent and Africa.
- Clonal spread is less significant than plasmid-mediated dissemination, though specific high-risk clones are involved in global dispersion.
- Phenotypic detection has improved but remains challenging, necessitating genotypic identification (sequencing).
- Emergence of bacteria with blaOXA-48, blaOXA-181, and blaOXA-232 is likely underreported.
Conclusions:
- OXA-48-like carbapenemases represent a significant and expanding global health threat.
- Improved laboratory detection methods are essential, particularly in non-endemic regions.
- Enhanced surveillance and clinical awareness are critical to manage outbreaks and prevent further spread.
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