1887

Abstract

The spread of carbapenem-resistant has led to a worldwide healthcare problem. Carbapenem resistance in is mainly mediated by the acquisition of the carbapenem-hydrolyzing oxacillinase OXA-23. The phenotypic detection of carbapenem-producing is challenging and time-consuming. Hence, there is an unmet medical need for reliable and rapid diagnostic tools to detect OXA-23-producing 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 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-23 by sandwich enzyme-linked immunosorbent assay (ELISA) and ICT. A well-characterized collection of carbapenem-resistant 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 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 isolates to other patients and healthcare workers.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001015
2019-07-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jmm/68/7/1021.html?itemId=/content/journal/jmm/10.1099/jmm.0.001015&mimeType=html&fmt=ahah

References

  1. Dijkshoorn L, Nemec A, Seifert H. An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii . Nat Rev Microbiol 2007; 5:939–951 [View Article]
    [Google Scholar]
  2. Nowak J, Zander E, Stefanik D, Higgins PG, Roca I et al. High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial. J Antimicrob Chemother 2017; 72:3277–3282 [View Article]
    [Google Scholar]
  3. Meletis G. Carbapenem resistance: overview of the problem and future perspectives. Ther Adv Infect Dis 2016; 3:15–21 [View Article]
    [Google Scholar]
  4. Hagihara M, Housman ST, Nicolau DP, Kuti JL. In vitro pharmacodynamics of polymyxin B and tigecycline alone and in combination against carbapenem-resistant Acinetobacter baumannii . Antimicrob Agents Chemother 2014; 58:874–879 [View Article]
    [Google Scholar]
  5. Mavroidi A, Likousi S, Palla E, Katsiari M, Roussou Z et al. Molecular identification of tigecycline- and colistin-resistant carbapenemase-producing Acinetobacter baumannii from a Greek hospital from 2011 to 2013. J Med Microbiol 2015; 64:993–997 [View Article]
    [Google Scholar]
  6. Cai Y, Chai D, Wang R, Liang B, Bai N. Colistin resistance of Acinetobacter baumannii: clinical reports, mechanisms and antimicrobial strategies. J Antimicrob Chemother 2012; 67:1607–1615 [View Article]
    [Google Scholar]
  7. Organization WH 2018; Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. http://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf
  8. Lee CR, Lee JH, Park M, Park KS, Bae IK et al. Biology of Acinetobacter baumannii: pathogenesis, antibiotic resistance mechanisms, and prospective treatment options. Front Cell Infect Microbiol 2017; 7:55 [View Article]
    [Google Scholar]
  9. Higgins PG, Dammhayn C, Hackel M, Seifert H. Global spread of carbapenem-resistant Acinetobacter baumannii . J Antimicrob Chemother 2010; 65:233–238 [View Article]
    [Google Scholar]
  10. Poirel L, Nordmann P. Carbapenem resistance in Acinetobacter baumannii: mechanisms and epidemiology. Clin Microbiol Infect 2006; 12:826–836 [View Article]
    [Google Scholar]
  11. Bonnin RA, Rotimi VO, Al Hubail M, Gasiorowski E, Al Sweih N et al. Wide dissemination of GES-type carbapenemases in Acinetobacter baumannii isolates in Kuwait. Antimicrob Agents Chemother 2013; 57:183–188 [View Article]
    [Google Scholar]
  12. Turton JF, Ward ME, Woodford N, Kaufmann ME, Pike R et al. The role of ISAba1 in expression of OXA carbapenemase genes in Acinetobacter baumannii . FEMS Microbiol Lett 2006; 258:72–77 [View Article]
    [Google Scholar]
  13. Higgins PG, Pérez-Llarena FJ, Zander E, Fernández A, Bou G et al. OXA-235, a novel class D β-lactamase involved in resistance to carbapenems in Acinetobacter baumannii . Antimicrob Agents Chemother 2013; 57:2121–2126 [View Article]
    [Google Scholar]
  14. Higgins PG, Poirel L, Lehmann M, Nordmann P, Seifert H. OXA-143, a novel carbapenem-hydrolyzing class D beta-lactamase in Acinetobacter baumannii . Antimicrob Agents Chemother 2009; 53:5035–5038 [View Article]
    [Google Scholar]
  15. ePoster E. 2018; Carbapenemase-encoding genes in Acinetobacter baumannii - results from a worldwide surveillance study. www.escmid.org/escmid_publications/escmid_elibrary/?q=higgins&tx_solr%5Bfilter%5D%5B0%5D=author%253ACarina%2BM%25C3%25BCller
  16. Huang XZ, Cash DM, Chahine MA, Nikolich MP, Craft DW. Development and validation of a multiplex TaqMan real-time PCR for rapid detection of genes encoding four types of class D carbapenemase in Acinetobacter baumannii . J Med Microbiol 2012; 61:1532–1537 [View Article]
    [Google Scholar]
  17. Higgins PG, Zander E, Seifert H. Identification of a novel insertion sequence element associated with carbapenem resistance and the development of fluoroquinolone resistance in Acinetobacter radioresistens . J Antimicrob Chemother 2013; 68:720–722 [View Article]
    [Google Scholar]
  18. Zander E, Fernández-González A, Schleicher X, Dammhayn C, Kamolvit W et al. Worldwide dissemination of acquired carbapenem-hydrolysing class D β-lactamases in Acinetobacter spp. other than Acinetobacter baumannii . Int J Antimicrob Agents 2014; 43:375–377 [View Article]
    [Google Scholar]
  19. Zander E, Chmielarczyk A, Heczko P, Seifert H, Higgins PG. Conversion of OXA-66 into OXA-82 in clinical Acinetobacter baumannii isolates and association with altered carbapenem susceptibility. J Antimicrob Chemother 2013; 68:308–311 [View Article]
    [Google Scholar]
  20. Zander E, Seifert H, Higgins PG, Saline Eof. Effects of saline, an ambient acidic environment, and sodium salicylate on OXA-mediated carbapenem resistance in Acinetobacter baumannii . Antimicrob Agents Chemother 2016; 60:3415–3418 [View Article]
    [Google Scholar]
  21. Moehring RW, Sloane R, Chen LF, Smathers EC, Schmader KE et al. Delays in appropriate antibiotic therapy for Gram-negative bloodstream infections: a multicenter, community hospital study. PLoS One 2013; 8:e76225 [View Article]
    [Google Scholar]
  22. Friedman ND, Carmeli Y, Walton AL, Schwaber MJ. Carbapenem-resistant Enterobacteriaceae: a strategic roadmap for infection control. Infect Control Hosp Epidemiol 2017; 38:580–594 [View Article]
    [Google Scholar]
  23. Riccobono E, Bogaerts P, Antonelli A, Evrard S, Giani T et al. Evaluation of the OXA-23 K-SeT® immunochromatographic assay for the rapid detection of OXA-23-like carbapenemase-producing Acinetobacter spp. J Antimicrob Chemother 20191455–145725Jan 2019 [View Article]
    [Google Scholar]
  24. Wareham DW, Shah R, Betts JW, Phee LM, Momin MH. Evaluation of an immunochromatographic lateral flow assay (OXA-48 K-SeT) for rapid detection of OXA-48-Like carbapenemases in Enterobacteriaceae. J Clin Microbiol 2016; 54:471–473 [View Article]
    [Google Scholar]
  25. Hamprecht A, Vehreschild JJ, Seifert H, Saleh A. Rapid detection of NDM, KPC and OXA-48 carbapenemases directly from positive blood cultures using a new multiplex immunochromatographic assay. PLoS One 2018; 13:e0204157 [View Article]
    [Google Scholar]
  26. Riccobono E, Antonelli A, Pecile P, Bogaerts P, D'Andrea MM et al. Evaluation of the KPC K-SeT® immunochromatographic assay for the rapid detection of KPC carbapenemase producers from positive blood cultures. J Antimicrob Chemother 2018; 73:539–540 [View Article]
    [Google Scholar]
  27. Greissl C, Saleh A, Hamprecht A. Rapid detection of OXA-48-like, KPC, NDM, and VIM carbapenemases in Enterobacterales by a new multiplex immunochromatographic test. Eur J Clin Microbiol Infect Dis 2019; 38:331-335 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001015
Loading
/content/journal/jmm/10.1099/jmm.0.001015
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error