OXA-23 - Science

The Global Ascendency of OXA-48-Type Carbapenemases

Pitout JDD, Peirano G, Kock MM, Strydom KA, Matsumura Y
Clin Microbiol Rev. 2019 Nov 13;33(1):e00102-19

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 bla OXA-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 bla OXA-48, bla OXA-181, and bla OXA-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.

https://pubmed.ncbi.nlm.nih.gov/31722889/

Generation and selection of antibodies for a novel immunochromatographic lateral flow test to rapidly identify OXA-23-like-mediated carbapenem resistance in Acinetobacter baumannii

Mertins S, Higgins PG, Rodríguez MG, Borlon C, Gilleman Q, Mertens P, Seifert H, Krönke M, Klimka A.
J Med Microbiol. 2019 Jul;68(7):1021-1032

Abstract
The spread of carbapenem-resistant Acinetobacter baumannii has led to a worldwide healthcare problem. Carbapenem resistance in A. baumannii is mainly mediated by the acquisition of the carbapenem-hydrolyzing oxacillinase OXA-23. The phenotypic detection of carbapenem-producing A. baumannii is challenging and time-consuming. Hence, there is an unmet medical need for reliable and rapid diagnostic tools to detect OXA-23-producing Acinetobacter isolates to enable successful patient management.
Development of an immunochromatographic lateral flow test (ICT) for the rapid and reliable detection of OXA-23-producing carbapenem-resistant Acinetobacter isolates.
For the development of an antibody-based ICT, we generated anti-OXA-23 monoclonal antibodies (MoAbs) and screened them sequentially for their ability to bind native OXA-23. Selected OXA-23-specific MoAbs were tested in different combinations for their capacity to capture and detect OXA-23His6 by sandwich enzyme-linked immunosorbent assay (ELISA) and ICT. A well-characterized collection of carbapenem-resistant Acinetobacter isolates with defined carbapenem resistance mechanisms were used to evaluate the specificity of the final OXA-23 ICT prototype.
The antibody pairs best suited for the sandwich ELISA format did not match the best pairs in the ICT format selected during the development process of the final prototype OXA-23 ICT. This prototype was able to differentiate between OXA-23 subfamily-mediated carbapenem resistance and carbapenem-resistant Acinetobacter isolates overexpressing other OXAs with 100 % specificity and a turnaround time of 20 min from culture plate to result.
With this rapid detection assay one can save 12-48 h of diagnostic time, which could help avoid inappropriate use of carbapenems and enable earlier intervention to control the transmission of OXA-23-producing carbapenem-resistant Acinetobacter isolates to other patients and healthcare workers.

https://pubmed.ncbi.nlm.nih.gov/31188094/

Evaluation of the OXA-23 K-SeTVR immunochromatographic assay for the rapid detection of OXA-23-like carbapenemase-producing Acinetobacter spp.

E. Riccobono, P. Bogaerts, A. Antonelli, S. Evrard, T.  Giani, G. M. Rossolini and Y. Glupczynski
J Clin Microbiol. 2019 Jan 25. doi: 10.1093
https://www.ncbi.nlm.nih.gov/pubmed/30689921

Evaluation of a new lateral flow assay for the detection of OXA-23-producing Bacteria.

Bogaerts P, Evrard S, Bouchahrouf W, Hoebeke M, Berhin C, Huang TD, and Glupczynski Y.
38e Réunion interdisciplinaire de chimiothérapie anti-infectieuse 17-18 décembre, 2018 Paris
Poster

Antibiotic resistance – quick and reliable detection.

Alexander Klimka and Paul Higgins
DZIF, German Center for Infection Research, 14 May 2018
http://www.dzif.de/en/news_media_centre/news_press_releases/view/detail/artikel/antibiotic_resistance_quick_and_reliable_detection/

Rapid identification of OXA-40 and OXA-58-subfamily in carbapenemresistant Acinetobacter baumannii with a novel immunochromatographic lateral flow assay.

S. Mertins, P. G. Higgins, Q. Gilleman, P. Mertens, H. Seifert, M. Krönke and A. Klimka.
28th European Congress of Clinical Microbiology and Infectious Diseases, Infectious Diseases April 21 – 24, 2018
Poster

Rapid identification of OXA-23-subfamily in carbapenem-resistant Acinetobacter spp. with a novel immunochromatographic lateral flow assay.

S. Mertins, P. G. Higgins, L. Denorme, Q. Gilleman, P. Mertens, H. Seifert, M. Krönke and Alexander Klimka.
27th European Congress of Clinical Microbiology and Infectious Diseases, Infectious Diseases April 22 – 25, 2017
Poster