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Volume 72, Issue 4

Development of an immunochromatographic lateral flow assay to rapidly detect OXA-23-, OXA-40-, OXA-58- and NDM-mediated carbapenem resistance determinants in Open Access

Abstract

infections can be extremely challenging to treat owing to the worldwide prevalence of multidrug-resistant isolates, especially against carbapenems. Colonization with carbapenem-resistant (CRAb) requires rapid action from an infection control perspective because the organism is known for its propensity for epidemic spread

There is an unmet medical need to rapidly identify CRAb to enable appropriate antimicrobial treatment and to prevent transmission

Our aim was to expand the OXA-detection abilities of the rapid immunochromatographic test (ICT) OXA-23 -SeT (Coris BioConcept) to include OXA-40- and OXA-58-like carbapenemases, which together confer carbapenem resistance to more than 94 % of CRAb isolates worldwide

We used hybridoma technology to generate mAbs against OXA-40 and OXA-58 and selected them for productivity and specificity against recombinant and endogenous OXA-40 and OXA-58. Combinations of the resulting mAbs were analysed in ICT format for their ability to detect recombinant rOXA-40 or rOXA-58, respectively. Subsequently, selected antibody pairs were implemented into single-OXA-40 or single-OXA-58 prototypes and the final OXA-23/40/58/NDM ICT and were evaluated on clinical spp. isolates with well-defined carbapenem resistance mechanisms

Five anti-OXA-40 and anti-OXA-58 mAbs were selected. Competition ELISA with combinations of these antibodies revealed that the anti-OXA-40 antibodies bind to one of two binding clusters on OXA-40, while anti-OXA-58 antibodies bind to one of four binding clusters on OXA-58. Direct binding to the corresponding antigen in an ICT format has left only three antibodies against rOXA-40 and rOXA-58, respectively for the subsequent sandwich ICT selection procedure, which revealed that the anti-OXA-40 (#5) and anti-OXA-58 (#A8) mAbs in combination with the cross-reactive mAb #C8 performed best. They were implemented into single-OXA-40 and single-OXA-58 ICT prototypes and evaluated. These single ICT prototypes demonstrated 100 % specificity and sensitivity. Based on these results, an OXA-23/40/58/NDM-ICT was developed, complemented with OXA-23 and NDM-specific detection. An evaluation with selected carbapenem-resistant spp. isolates (=34) showed 100 % specificity

With this easy-to-use detection assay, one can save 12–48 h in diagnostics, which helps to treat patients earlier with appropriate antibiotics and allows immediate intervention to control transmission of CRAb

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Acinetobacter baumannii , carbapenem resistance , carbapenemase , immunochromatographic test (ICT) , lateral flow assay (LFA) , oxacillinase (OXA) and rapid diagnostic test
Funding
This study was supported by the:
  • European Regional Development Fund (Award RADAR#7769)
    • Principle Award Recipient: PascalMertens
  • Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen (Award 323-8.04.10.02-141905)
    • Principle Award Recipient: MartinKrönke
  • Deutsches Zentrum für Infektionsforschung (Award 8018808912, 8018808917, 8018708712)
    • Principle Award Recipient: AlexanderKlimka
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2023-04-12
2024-10-03
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Development of an immunochromatographic lateral flow assay to rapidly detect OXA-23-, OXA-40-, OXA-58- and NDM-mediated carbapenem resistance determinants in Acinetobacter baumannii
J. Med. Microbiol. 72, 001681 (2023); https://doi.org/10.1099/jmm.0.001681
/content/journal/jmm/10.1099/jmm.0.001681
/content/journal/jmm/10.1099/jmm.0.001681
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