Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Minimum inhibitory concentrations of aztreonam–avibactam, ceftazidime–avibactam and meropenem in clinical isolates of Klebsiella pneumoniae harboring carbapenemase genes

Abstract

This study was aimed at understanding the distributions of the MICs (minimum inhibitory concentrations) of aztreonam–avibactam, ceftazidime–avibactam and meropenem with respect to Klebsiella pneumoniae isolates producing different types of carbapenemases and their combinations. K. pneumoniae isolates were collected between 2019 and 2022 from 37 hospitals. PCR was used to screen for blaKPC-, blaNDM- and blaOXA-48-like genes. MICs were determined by the broth microdilution method for meropenem, aztreonam–avibactam and ceftazidime–avibactam at a constant avibactam concentration of 4 mg l−1. MIC distributions were analyzed for groups of isolates based on the identified carbapenemases including their combinations. The AZT/AVI MIC50 and MIC90 for all NDM-positive isolates were 0.25 and 0.5, respectively, and for serine-carbapenemase-only producers, they were 0.25 and 1 mg l−1, respectively. The CZD/AVI MIC50 and MIC90 values for serine-carbapenemase-only producers were 1 and 4 mg l−1, respectively. The AZT/AVI MIC50 and MIC90 values for co-producers and single carbapenemase producers were the same (i.e., 0.25 and 1 mg l−1, respectively). The total proportion of meropenem-susceptible isolates (≤8 mg l−1) among all the carbapenemase producers was 25.1% (31.1% among single-carbapenemase producers and 9.2% among co-producers). The results support the use of aztreonam–avibactam for the empirical treatment of infections caused by any carbapenemase producers.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

References

  1. Hallal Ferreira Raro O, Nordmann P, Dominguez Pino M, Findlay J, Poirel L. Emergence of carbapenemase-producing Hypervirulent Klebsiella pneumoniae in Switzerland. Antimicrob Agents Chemother. 2023;67:e0142422. https://doi.org/10.1128/aac.01424-22.

    Article  CAS  PubMed  Google Scholar 

  2. Titov I, Wunderink RG, Roquilly A, Rodriguez Gonzalez D, David-Wang A, Boucher HW, et al. A randomized, double-blind, multicenter trial comparing efficacy and safety of imipenem/cilastatin/relebactam versus piperacillin/tazobactam in adults with hospital-acquired or ventilator-associated bacterial pneumonia (RESTORE-IMI 2 Study). Clin Infect Dis. 2021;73:e4539–48. https://doi.org/10.1093/cid/ciaa803.

    Article  PubMed  Google Scholar 

  3. Castanheira M, Deshpande LM, Mendes RE, Doyle TB, Sader HS. Prevalence of carbapenemase genes among carbapenem-nonsusceptible Enterobacterales collected in US hospitals in a five-year period and activity of ceftazidime/avibactam and comparator agents. JAC Antimicrob Resist. 2022;4:dlac098. https://doi.org/10.1093/jacamr/dlac098.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Papadimitriou-Olivgeris M, Bartzavali C, Karachalias E, Spiliopoulou A, Tsiata E, Siakallis G, et al. A seven-year microbiological and molecular study of bacteremias due to carbapenemase-producing Klebsiella pneumoniae: an interrupted time-series analysis of changes in the carbapenemase gene’s distribution after introduction of ceftazidime/avibactam. Antibiotics. 2022;11. https://doi.org/10.3390/antibiotics11101414.

  5. Bonnin RA, Bernabeu S, Emeraud C, Naas T, Girlich D, Jousset AB, et al. In vitro activity of imipenem-relebactam, meropenem-vaborbactam, ceftazidime–avibactam and comparators on carbapenem-resistant non-carbapenemase-producing enterobacterales. Antibiotics. 2023;12. https://doi.org/10.3390/antibiotics12010102.

  6. Bhatnagar A, Boyd S, Sabour S, Bodnar J, Nazarian E, Peinovich N, et al. Aztreonam–avibactam susceptibility testing program for metallo-beta-lactamase-producing enterobacterales in the antibiotic resistance laboratory network, March 2019 to December 2020. Antimicrob Agents Chemother. 2021;65:e0048621. https://doi.org/10.1128/aac.00486-21.

    Article  CAS  PubMed  Google Scholar 

  7. Esposito S, Stone GG, Papaparaskevas J. In vitro activity of aztreonam/avibactam against a global collection of Klebsiella pneumoniae collected from defined culture sources in 2016 and 2017. J Glob Antimicrob Resist. 2021;24:14–22. https://doi.org/10.1016/j.jgar.2020.08.004.

    Article  CAS  PubMed  Google Scholar 

  8. Lee TD, Adie K, McNabb A, Purych D, Mannan K, Azana R, et al. Rapid detection of KPC, NDM, and OXA-48-like carbapenemases by real-time PCR from rectal swab surveillance samples. J Clin Microbiol. 2015;53:2731–3. https://doi.org/10.1128/jcm.01237-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mauri C, Maraolo AE, Di Bella S, Luzzaro F, Principe L. The revival of aztreonam in combination with avibactam against metallo-beta-lactamase-producing gram-negatives: a systematic review of in vitro studies and clinical cases. Antibiotics. 2021;10. https://doi.org/10.3390/antibiotics10081012.

  10. Lee CR, Lee JH, Park KS, Kim YB, Jeong BC, Lee SH. Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol. 2016;7:895. https://doi.org/10.3389/fmicb.2016.00895.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Livermore DM, Andrews JM, Hawkey PM, Ho PL, Keness Y, Doi Y, et al. Are susceptibility tests enough, or should laboratories still seek ESBLs and carbapenemases directly? J Antimicrob Chemother. 2012;67:1569–77.

    Article  CAS  PubMed  Google Scholar 

  12. Livermore DM, Mushtaq S, Vickers A, Woodford N. Activity of aztreonam/avibactam against metallo-beta-lactamase-producing enterobacterales from the UK: impact of penicillin-binding protein-3 inserts and CMY-42 beta-lactamase in Escherichia coli. Int J Antimicrob Agents. 2023:106776. https://doi.org/10.1016/j.ijantimicag.2023.106776.

Download references

Acknowledgements

The authors are grateful to the technical specialist Olga Gul.

Funding

This research was funded by the Russian Science Foundation, grant number 21-74-10090.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vladimir Ageevets.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

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

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ageevets, V., Sulian, O., Avdeeva, A. et al. Minimum inhibitory concentrations of aztreonam–avibactam, ceftazidime–avibactam and meropenem in clinical isolates of Klebsiella pneumoniae harboring carbapenemase genes. J Antibiot (2024). https://doi.org/10.1038/s41429-024-00758-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41429-024-00758-8

Search

Quick links