Skip to main content
SpringerLink
Log in

Detection of carbapenemase producers by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS)

  • Review
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been recently applied in detection of carbapenemase-producing Gram-negative isolates. In the present study, we review the latest developments in this field.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hrabák J, Walková R, Studentová V, Chudácková E, Bergerová T (2011) Carbapenemase activity detection by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 49:3222–3227. https://doi.org/10.1128/JCM.00984-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Burckhardt I, Zimmermann S (2011) Using matrix-assisted laser desorption ionization-time of flight mass spectrometry to detect carbapenem resistance within 1 to 2.5 hours. J Clin Microbiol 49:3321–3324. https://doi.org/10.1128/JCM.00287-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kempf M, Bakour S, Flaudrops C, Berrazeg M, Brunel JM, Drissi M et al (2012) Rapid detection of carbapenem resistance in Acinetobacter baumannii using matrix-assisted laser desorption ionization-time of flight mass spectrometry. PLoS One 7(2):e31676. https://doi.org/10.1371/journal.pone.0031676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hrabák J, Studentová V, Walková R, Zemlicková H, Jakubu V, Chudácková E et al (2012) Detection of NDM-1, VIM-1, KPC, OXA-48, and OXA-162 carbapenemases by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 50:2441–2443. https://doi.org/10.1128/JCM.01002-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sparbier K, Schubert S, Weller U, Boogen C, Kostrzewa M (2012) Matrix-assisted laser desorption ionization-time of flight mass spectrometry-based functional assay for rapid detection of resistance against β-lactam antibiotics. J Clin Microbiol 50:927–937. https://doi.org/10.1128/JCM.05737-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Carvalhaes CG, Cayô R, Assis DM, Martins ER, Juliano L, Juliano MA et al (2013) Detection of SPM-1-producing Pseudomonas aeruginosa and class D β-lactamase-producing Acinetobacter baumannii isolates by use of liquid chromatography-mass spectrometry and matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 51:287–290. https://doi.org/10.1128/JCM.02365-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Álvarez-Buylla A, Picazo JJ, Culebras E (2013) Optimized method for Acinetobacter species carbapenemase detection and identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 51:1589–1592. https://doi.org/10.1128/JCM.00181-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wang L, Han C, Sui W, Wang M, Lu X (2013) MALDI-TOF MS applied to indirect carbapenemase detection: a validated procedure to clearly distinguish between carbapenemase-positive and carbapenemase-negative bacterial strains. Anal Bioanal Chem 405:5259–5266. https://doi.org/10.1007/s00216-013-6913-2

    Article  CAS  PubMed  Google Scholar 

  9. Hoyos-Mallecot Y, Cabrera-Alvargonzalez JJ, Miranda-Casas C, Rojo-Martín MD, Liebana-Martos C, Navarro-Marí JM (2014) MALDI-TOF MS, a useful instrument for differentiating metallo-β-lactamases in Enterobacteriaceae and Pseudomonas spp. Lett Appl Microbiol 58:325–329. https://doi.org/10.1111/lam.12203

    Article  CAS  PubMed  Google Scholar 

  10. Johansson A, Ekelöf J, Giske CG, Sundqvist M (2014) The detection and verification of carbapenemases using ertapenem and Matrix Assisted Laser Desorption Ionization-Time of Flight. BMC Microbiol 14:89. https://doi.org/10.1186/1471-2180-14-89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sauget M, Cabrolier N, Manzoni M, Bertrand X, Hocquet D (2014) Rapid, sensitive and specific detection of OXA-48-like-producing Enterobacteriaceae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Microbiol Methods 105:88–91. https://doi.org/10.1016/j.mimet.2014.07.004

    Article  CAS  PubMed  Google Scholar 

  12. Knox J, Jadhav S, Sevior D, Agyekum A, Whipp M, Waring L et al (2014) Phenotypic detection of carbapenemase-producing Enterobacteriaceae by use of matrix-assisted laser desorption ionization-time of flight mass spectrometry and the Carba NP test. J Clin Microbiol 52(11):4075–4077. https://doi.org/10.1128/JCM.02121-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Carvalhaes CG, da Silva AC, Streling AP, Cayô R, Rockstroh AC, Machado AM, Gales AC (2015) Detection of carbapenemase activity using VITEK MS: interplay of carbapenemase type and period of incubation. J Med Microbiol 64:946–947. https://doi.org/10.1099/jmm.0.000102

    Article  CAS  PubMed  Google Scholar 

  14. Studentova V, Papagiannitsis CC, Izdebski R, Pfeifer Y, Chudackova E, Bergerova T et al (2015) Detection of OXA-48-type carbapenemase-producing Enterobacteriaceae in diagnostic laboratories can be enhanced by addition of bicarbonates to cultivation media or reaction buffers. Folia Microbiol (Praha) 60:119–129. https://doi.org/10.1007/s12223-014-0349-8

    Article  CAS  Google Scholar 

  15. Papagiannitsis CC, Študentová V, Izdebski R, Oikonomou O, Pfeifer Y, Petinaki E et al (2015) Matrix-assisted laser desorption ionization-time of flight mass spectrometry meropenem hydrolysis assay with NH4HCO3, a reliable tool for direct detection of carbapenemase activity. J Clin Microbiol 53:1731–1735. https://doi.org/10.1128/JCM.03094-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mirande C, Canard I, Buffet Croix Blanche S, Charrier JP, van Belkum A, Welker M et al (2015) Rapid detection of carbapenemase activity: benefits and weaknesses of MALDI-TOF MS. Eur J Clin Microbiol Infect Dis 34:2225–2234. https://doi.org/10.1007/s10096-015-2473-z

    Article  CAS  PubMed  Google Scholar 

  17. Monteferrante CG, Sultan S, Ten Kate MT, Dekker LJ, Sparbier K, Peer M, Kostzrewa M et al (2016) Evaluation of different pretreatment protocols to detect accurately clinical carbapenemase-producing Enterobacteriaceae by MALDI-TOF. J Antimicrob Chemother 71:2856–2867. https://doi.org/10.1093/jac/dkw208

    Article  CAS  PubMed  Google Scholar 

  18. Ramos AC, Carvalhaes CG, Cordeiro-Moura JR, Rockstroh AC, Machado AMO, Gales AC (2016) Influence of culture media on detection of carbapenem hydrolysis by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 54:1896–1898. https://doi.org/10.1128/JCM.00749-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Oviaño M, Bou G (2017) Imipenem-avibactam: a novel combination for the rapid detection of carbapenemase activity in Enterobacteriaceae and Acinetobacter baumannii by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Diagn Microbiol Infect Dis 87:129–132. https://doi.org/10.1016/j.diagmicrobio.2016.10.016

    Article  CAS  PubMed  Google Scholar 

  20. Knox J, Palombo E (2017) Performance of a MALDI-TOF MS-based imipenem hydrolysis assay incorporating zinc sulfate. Diagn Microbiol Infect Dis 87:258–260. https://doi.org/10.1016/j.diagmicrobio.2016.11.018

    Article  CAS  PubMed  Google Scholar 

  21. Calderaro A, Buttrini M, Piergianni M, Montecchini S, Martinelli M, Covan S et al (2017) Evaluation of a modified meropenem hydrolysis assay on a large cohort of KPC and VIM carbapenemase-producing Enterobacteriaceae. PLoS One 12(4):e0174908. https://doi.org/10.1371/journal.pone.0174908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Miltgen G, Plésiat P, Mille A, Chatelain P, Fournier D (2018) Detection of carbapenemase activity in Pseudomonas aeruginosa by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). J Microbiol Methods 145:66–68. https://doi.org/10.1016/j.mimet.2017.12.011

    Article  CAS  PubMed  Google Scholar 

  23. Chang KC, Chung CY, Yeh CH, Hsu KH, Chin YC, Huang SS et al (2018) Direct detection of carbapenemase-associated proteins of Acinetobacter baumannii using nanodiamonds coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Microbiol Methods 147:36–42. https://doi.org/10.1016/j.mimet.2018.02.014

    Article  CAS  PubMed  Google Scholar 

  24. Lee W, Chung HS, Lee Y, Yong D, Jeong SH, Lee K et al (2013) Comparison of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry assay with conventional methods for detection of IMP-6, VIM-2, NDM-1, SIM-1, KPC-1, OXA-23, and OXA-51 carbapenemase-producing Acinetobacter spp., Pseudomonas aeruginosa, and Klebsiella pneumoniae. Diagn Microbiol Infect Dis 77:227–230. https://doi.org/10.1016/j.diagmicrobio.2013.07.005

    Article  CAS  PubMed  Google Scholar 

  25. Vogne C, Prod’hom G, Jaton K, Decosterd LA, Greub G (2014) A simple, robust and rapid approach to detect carbapenemases in Gram-negative isolates by MALDI-TOF mass spectrometry: validation with triple quadripole tandem mass spectrometry, microarray and PCR. Clin Microbiol Infect 20:O1106–O1112. https://doi.org/10.1111/1469-0691.12715

    Article  CAS  PubMed  Google Scholar 

  26. Chong PM, McCorrister SJ, Unger MS, Boyd DA, Mulvey MR, Westmacott GR (2015) MALDI-TOF MS detection of carbapenemase activity in clinical isolates of Enterobacteriaceae spp., Pseudomonas aeruginosa, and Acinetobacter baumannii compared against the Carba-NP assay. J Microbiol Methods 111:21–23. https://doi.org/10.1016/j.mimet.2015.01.024

    Article  CAS  PubMed  Google Scholar 

  27. Hrabák J (2015) Detection of carbapenemases using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) meropenem hydrolysis assay. Methods Mol Biol 1237:91–96. https://doi.org/10.1007/978-1-4939-1776-1_9

    Article  CAS  PubMed  Google Scholar 

  28. Lasserre C, De Saint Martin L, Cuzon G, Bogaerts P, Lamar E, Glupczynski Y et al (2015) Efficient detection of carbapenemase activity in Enterobacteriaceae by matrix-assisted laser desorption ionization-time of flight mass spectrometry in less than 30 minutes. J Clin Microbiol 53:2163–2171. https://doi.org/10.1128/JCM.03467-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Abouseada N, Raouf M, El-Attar E, Moez P (2017) Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry rapid detection of carbapenamase activity in Acinetobacter baumannii isolates. Indian J Med Microbiol 35:85–89. https://doi.org/10.4103/0255-0857.202335

    Article  PubMed  Google Scholar 

  30. Choquet M, Guiheneuf R, Castelain S, Cattoir V, Auzou M, Pluquet E et al (2018) Comparison of MALDI-ToF MS with the Rapidec Carba NP test for the detection of carbapenemase-producing Enterobacteriaceae. Eur J Clin Microbiol Infect Dis 37:149–155. https://doi.org/10.1007/s10096-017-3115-4

    Article  CAS  PubMed  Google Scholar 

  31. Hrabák J, Chudáčková E, Papagiannitsis CC (2014) Detection of carbapenemases in Enterobacteriaceae: a challenge for diagnostic microbiological laboratories. Clin Microbiol Infect 20:839–853. https://doi.org/10.1111/1469-0691.12678

    Article  PubMed  Google Scholar 

  32. Oviaño M, Bou G (2018) Matrix-assisted laser desorption ionization-time of flight mass spectrometry for the rapid detection of antimicrobial resistance mechanisms and beyond. Clin Microbiol Rev 28;32(1):pii: e00037–18. https://doi.org/10.1128/CMR.00037-18

    Article  Google Scholar 

  33. Rapp E, Samuelsen Ø, Sundqvist M (2018) Detection of carbapenemases with a newly developed commercial assay using matrix assisted laser desorption ionization-time of flight. J Microbiol Methods 146:37–39. https://doi.org/10.1016/j.mimet.2018.01.008

    Article  CAS  PubMed  Google Scholar 

  34. Dortet L, Tandé D, de Briel D, Bernabeu S, Lasserre C, Gregorowicz G et al (2018) MALDI-TOF for the rapid detection of carbapenemase-producing Enterobacteriaceae: comparison of the commercialized MBT STAR®-Carba IVD kit with two in-house MALDI-TOF techniques and the RAPIDEC® CARBA NP. J Antimicrob Chemother 73:2352–2359. https://doi.org/10.1093/jac/dky209

    Article  CAS  PubMed  Google Scholar 

  35. Jung JS, Popp C, Sparbier K, Lange C, Kostrzewa M, Schubert S (2014) Evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry for rapid detection of b-lactam resistance in Enterobacteriaceae derived from blood cultures. J Clin Microbiol 52:924–930. https://doi.org/10.1128/JCM.02691-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Carvalhaes CG, Cayô R, Visconde MF, Barone T, Frigatto EA, Okamoto D et al (2014) Detection of carbapenemase activity directly from blood culture vials using MALDI-TOF MS: a quick answer for the right decision. J Antimicrob Chemother 69:2132–2136. https://doi.org/10.1093/jac/dku094

    Article  CAS  PubMed  Google Scholar 

  37. Hoyos-Mallecot Y, Riazzo C, Miranda-Casas C, Rojo-Martín MD, Gutiérrez-Fernández J, Navarro-Marí JM (2014) Rapid detection and identification of strains carrying carbapenemases directly from positive blood cultures using MALDI-TOF MS. J Microbiol Methods 105:98–101. https://doi.org/10.1016/j.mimet.2014.07.016

    Article  CAS  PubMed  Google Scholar 

  38. Fernández J, Rodríguez-Lucas C, Fernández-Suárez J, Vazquez F, Rodicio MR (2016) Identification of Enterobacteriaceae and detection of carbapenemases from positive blood cultures by combination of MALDI-TOF MS and Carba NP performed after four hour subculture in Mueller Hinton. J Microbiol Methods 129:133–135. https://doi.org/10.1016/j.mimet.2016.08.014

    Article  CAS  PubMed  Google Scholar 

  39. Ghebremedhin B, Halstenbach A, Smiljanic M, Kaase M, Ahmad-Nejad P (2016) MALDI-TOF MS based carbapenemase detection from culture isolates and from positive blood culture vials. Ann Clin Microbiol Antimicrob 15:5. https://doi.org/10.1186/s12941-016-0120-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sakarikou C, Ciotti M, Dolfa C, Angeletti S, Favalli C (2017) Rapid detection of carbapenemase-producing Klebsiella pneumoniae strains derived from blood cultures by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). BMC Microbiol. https://doi.org/10.1186/s12866-017-0952-3

  41. Yu J, Liu J, Li Y, Yu J, Zhu W, Liu Y et al (2018) Rapid detection of carbapenemase activity of Enterobacteriaceae isolated from positive blood cultures by MALDI-TOF MS. Ann Clin Microbiol Antimicrob 17:22. https://doi.org/10.1186/s12941-018-0274-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Oviaño M, Sparbier K, Barba MJ, Kostrzewa M, Bou G (2016) Universal protocol for the rapid automated detection of carbapenem-resistant Gram-negative bacilli directly from blood cultures by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS). Int J Antimicrob Agents 48(6):655–660. https://doi.org/10.1016/j.ijantimicag.2016.08.024

    Article  CAS  PubMed  Google Scholar 

  43. Oviaño M, Ramírez CL, Barbeyto LP, Bou G (2017) Rapid direct detection of carbapenemase-producing Enterobacteriaceae in clinical urine samples by MALDI-TOF MS analysis. J Antimicrob Chemother 72:1350–1354. https://doi.org/10.1093/jac/dkw579

    Article  CAS  PubMed  Google Scholar 

  44. Lau AF, Wang H, Weingarten RA, Drake SK, Suffredini AF, Garfield MK, Chen Y et al (2014) A rapid matrix-assisted laser desorption ionization-time of flight mass spectrometry-based method for single-plasmid tracking in an outbreak of carbapenem-resistant Enterobacteriaceae. J Clin Microbiol 52:2804–2812. https://doi.org/10.1128/JCM.00694-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Youn JH, Drake SK, Weingarten RA, Frank KM, Dekker JP, Lau AF (2016) Clinical performance of a matrix-assisted laser desorption ionization-time of flight mass spectrometry method for detection of certain blaKPC-containing plasmids. J Clin Microbiol 54:35–42. https://doi.org/10.1128/JCM.01643-15

    Article  CAS  PubMed  Google Scholar 

  46. Gaibani P, Galea A, Fagioni M, Ambretti S, Sambri V, Landini MP (2016) Evaluation of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of KPC-producing Klebsiella pneumoniae. J Clin Microbiol 54:2609–2613. https://doi.org/10.1128/JCM.01242-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Centonze AR, Bertoncelli A, Savio C, Orza P, Bedenić B, Mazzariol A (2018) Evaluation of rapid KPC carbapenemase detection method based on MALDI-TOF VITEK MS spectra analysis. J Med Microbiol 67:1474–1479. https://doi.org/10.1099/jmm.0.000831

    Article  CAS  PubMed  Google Scholar 

  48. Cordovana M, Kostrzewa M, Glandorf J, Bienia M, Ambretti S, Pranada AB (2018) A full MALDI-based approach to detect plasmid-encoded KPC-producing Klebsiella pneumoniae. Front Microbiol 9:2854. https://doi.org/10.3389/fmicb.2018.02854

    Article  PubMed  PubMed Central  Google Scholar 

  49. Figueroa-Espinosa R, Costa A, Cejas D, Barrios R, Vay C, Radice M et al (2019) MALDI-TOF MS based procedure to detect KPC-2 directly from positive blood culture bottles and colonies. J Microbiol Methods pii: S0167-7012(18)30920-5. https://doi.org/10.1016/j.mimet.2019.02.020

    Article  CAS  Google Scholar 

  50. Idelevich EA, Sparbier K, Kostrzewa M, Becker K (2018) Rapid detection of antibiotic resistance by MALDI-TOF mass spectrometry using a novel direct-on-target microdroplet growth assay. Clin Microbiol Infect 24:738–743. https://doi.org/10.1016/j.cmi.2017.10.016

    Article  CAS  PubMed  Google Scholar 

  51. Idelevich EA, Storck LM, Sparbier K, Drews O, Kostrzewa M, Becker K (2018) Rapid direct susceptibility testing from positive blood cultures by the matrix-assisted laser desorption ionization-time of flight mass spectrometry-based direct-on-target microdroplet growth assay. J Clin Microbiol 56(10):pii: e00913–18. https://doi.org/10.1128/JCM.00913-18

    Article  Google Scholar 

  52. Correa-Martínez CL, Idelevich EA, Sparbier K, Kostrzewa M, Becker K (2019) Rapid detection of extended-spectrum β-lactamases (ESBL) and AmpC β-lactamases in Enterobacterales: development of a screening panel using the MALDI-TOF MS-based direct-on-target microdroplet growth assay. Front Microbiol 24(10):13. https://doi.org/10.3389/fmicb.2019.00013

    Article  Google Scholar 

  53. Neonakis I, Spandidos D (2019) MALDI-TOF mass spectometry-based direct-on-target microdroplet growth assay: a novel assay for susceptibility testing and beyond. Future Microbiol. https://doi.org/10.2217/fmb-2019-0106

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Microbiology and Microbial Pathogenesis, University Hospital of Heraklion, 71201, Heraklion, Greece

    Ioannis K. Neonakis

  2. Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003, Heraklion, Greece

    Demetrios A. Spandidos

Authors
  1. Ioannis K. Neonakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Demetrios A. Spandidos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ioannis K. Neonakis.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethic approval

No ethical approval was required.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Neonakis, I.K., Spandidos, D.A. Detection of carbapenemase producers by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). Eur J Clin Microbiol Infect Dis 38, 1795–1801 (2019). https://doi.org/10.1007/s10096-019-03620-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-019-03620-0

Keywords

Search

Navigation