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Surveillance Open Access
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Abstract

BACKGROUND

Carbapenemase-producing Enterobacterales (CPE) cause infections, particularly nosocomially, with limited treatment options. NDM-1-producing cases have substantially increased since 2022, associated with the Ukraine war.

AIM

We aimed to investigate transmission patterns using Germany’s Integrated Genomic Surveillance (IGS), combining notifications and sequence data.

METHODS

We selected NDM-1-producing cases, confirmed by isolates between 1 January 2022 and 28 February 2023. Isolates were Illumina whole genome-sequenced and linked to notifications. Clusters were defined as ≤ 12 allelic differences in core genome-wide single nucleotide variant-based genotyping. Cluster categories were: ‘no exposure abroad’, ‘exposure in Ukraine’ or ‘other exposure abroad’ if ≥ one case stayed in Ukraine or elsewhere. Follow-up of 13 clusters examined further exposure information.

RESULTS

Among 424 cases of most frequent sequence types, 326 (77%) belonged to 61 clusters. Seventeen (28%) clusters were associated with no exposure abroad, 33 (54%) with exposure in Ukraine, seven (11%) with other exposure abroad, and four (7%) had insufficient data. Cases in clusters with exposure in Ukraine were more dispersed, younger, and more often wound-infected than in other exposure location categories (p < 0.01). Cluster follow-up revealed one cluster with all cases from Ukraine or Russia, another with nosocomial transmission following case importation, and a third with all cases from one German hospital without exposure abroad.

CONCLUSION

Most cases were in clusters, suggesting preventable chains of transmission. Three patterns emerged: transmission abroad, transmission in German hospitals from imported cases or local outbreaks. IGS can identify where transmission could be interrupted. International cooperation needs strengthening to prevent CPE spread.

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2026-01-08
2026-01-24
/content/10.2807/1560-7917.ES.2026.31.1.2500378
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References

  1. Murray CJL, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar G, Gray A, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399(10325):629-55.  https://doi.org/10.1016/S0140-6736(21)02724-0  PMID: 35065702 
  2. Wyres KL, Lam MMC, Holt KE. Population genomics of Klebsiella pneumoniae. Nat Rev Microbiol. 2020;18(6):344-59.  https://doi.org/10.1038/s41579-019-0315-1  PMID: 32055025 
  3. European Centre for Disease Prevention and Control (ECDC). Carbapenem-resistant Enterobacteriaceae, second update. Stockholm: ECDC; 2019. Available from: https://www.ecdc.europa.eu/en/publications-data/carbapenem-resistant-enterobacteriaceae-second-update
  4. Robert Koch-Institut (RKI). Infektionsepidemiologisches Jahrbuch meldepflichtiger Krankheiten für 2022. [Infection Epidemiology Yearbook of Notifiable Diseases for 2022]. Berlin: RKI; 2024. Available from: https://edoc.rki.de/handle/176904/11825.2
  5. Sandfort M, Hans JB, Fischer MA, Reichert F, Cremanns M, Eisfeld J, et al. Increase in NDM-1 and NDM-1/OXA-48-producing Klebsiella pneumoniae in Germany associated with the war in Ukraine, 2022. Euro Surveill. 2022;27(50):2200926.  https://doi.org/10.2807/1560-7917.ES.2022.27.50.2200926  PMID: 36695468 
  6. Pfennigwerth N, Cremanns M, Eisfeld J, Hans J, Anders A, Gatermann S. Bericht des Nationalen Referenzzentrums für gramnegative Krankenhauserreger – Zeitraum 1. Januar 2022 bis 31. Dezember 2022. Epid Bull.2023;27:3-10. German.  https://doi.org/10.25646/11589 
  7. UNHCR. Estimated number of refugees from Ukraine recorded in Europe and Asia since February 2022 as of July 2024, by selected country. Hamburg: Statista; 7 Feb 2025. Available from: https://www.statista.com/statistics/1312584/ukrainian-refugees-by-country
  8. Pfennigwerth N, Gatermann SG, Körber-Irrgang B, Hönings R. Phenotypic detection and differentiation of carbapenemase classes including OXA-48-like enzymes in Enterobacterales and Pseudomonas aeruginosa by a highly specialized micronaut-S microdilution assay. J Clin Microbiol. 2020;58(11):e00171-20.  https://doi.org/10.1128/JCM.00171-20  PMID: 32878951 
  9. Andrews S. FastQC: a quality control tool for high throughput sequence data. Cambridge: Github. [Accessed: 7 Feb 2025]. Available from: https://github.com/s-andrews
  10. Ondov BD, Starrett GJ, Sappington A, Kostic A, Koren S, Buck CB, et al. Mash Screen: high-throughput sequence containment estimation for genome discovery. Genome Biol. 2019;20(1):232.  https://doi.org/10.1186/s13059-019-1841-x  PMID: 31690338 
  11. Ondov BD, Treangen TJ, Melsted P, Mallonee AB, Bergman NH, Koren S, et al. Mash: fast genome and metagenome distance estimation using MinHash. Genome Biol. 2016;17(1):132.  https://doi.org/10.1186/s13059-016-0997-x  PMID: 27323842 
  12. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M, Kulikov AS, et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol. 2012;19(5):455-77.  https://doi.org/10.1089/cmb.2012.0021  PMID: 22506599 
  13. Prjibelski A, Antipov D, Meleshko D, Lapidus A, Korobeynikov A. Using SPAdes de novo assembler. Curr Protoc Bioinformatics. 2020;70(1):e102.  https://doi.org/10.1002/cpbi.102  PMID: 32559359 
  14. Gurevich A, Saveliev V, Vyahhi N, Tesler G. QUAST: quality assessment tool for genome assemblies. Bioinformatics. 2013;29(8):1072-5.  https://doi.org/10.1093/bioinformatics/btt086  PMID: 23422339 
  15. Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, et al. Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. 1995;33(9):2233-9.  https://doi.org/10.1128/jcm.33.9.2233-2239.1995  PMID: 7494007 
  16. Letunic I, Bork P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. 2021;49(W1):W293-6.  https://doi.org/10.1093/nar/gkab301  PMID: 33885785 
  17. Linkevicius M, Alm E, Roer L, Svartström O, Dada-Olorunwa M, Räisänen K, et al. Cross-border spread of a mosaic resistance (OXA-48) and virulence (aerobactin) plasmid in Klebsiella pneumoniae: a European Antimicrobial Resistance Genes Surveillance Network investigation, Europe, February 2019 to October 2024. Euro Surveill. 2025;30(27):2500439.  https://doi.org/10.2807/1560-7917.ES.2025.30.27.2500439  PMID: 40642770 
  18. Pfennigwerth N, Schauer J. Bericht des Nationalen Referenzzentrums für gramnegative Krankenhauserreger – Zeitraum 1. Januar 2021 bis 31. Dezember 2021.[Report of the National Reference Center for Gram-negative Hospital Pathogens Period January 1, 2021 to December 31, 2021]. Epid Bull.2022;19:3-9. German.  https://doi.org/10.25646/10034 
  19. Becker L, Kaase M, Pfeifer Y, Fuchs S, Reuss A, von Laer A, et al. Genome-based analysis of Carbapenemase-producing Klebsiella pneumoniae isolates from German hospital patients, 2008-2014. Antimicrob Resist Infect Control. 2018;7(1):62.  https://doi.org/10.1186/s13756-018-0352-y  PMID: 29744043 
  20. Zwittink RD, Wielders CC, Notermans DW, Verkaik NJ, Schoffelen AF, Witteveen S, et al. Multidrug-resistant organisms in patients from Ukraine in the Netherlands, March to August 2022. Euro Surveill. 2022;27(50):2200896.  https://doi.org/10.2807/1560-7917.ES.2022.27.50.2200896  PMID: 36695467 
  21. Schultze T, Hogardt M, Velázquez ES, Hack D, Besier S, Wichelhaus TA, et al. Molecular surveillance of multidrug-resistant Gram-negative bacteria in Ukrainian patients, Germany, March to June 2022. Euro Surveill. 2023;28(1):2200850.  https://doi.org/10.2807/1560-7917.ES.2023.28.1.2200850  PMID: 36695452 
  22. Kovalchuk V, Kondratiuk V, McGann P, Jones BT, Fomina N, Nazarchuk O, et al. Temporal evolution of bacterial species and their antimicrobial resistance characteristics in wound infections of war-related injuries in Ukraine from 2014 to 2023. J Hosp Infect. 2024;152:99-104.  https://doi.org/10.1016/j.jhin.2024.06.011  PMID: 38997008 
  23. Witteveen S, Hans JB, Izdebski R, Hasman H, Samuelsen Ø, Dortet L, et al. Dissemination of extensively drug-resistant NDM-producing Providencia stuartii in Europe linked to patients transferred from Ukraine, March 2022 to March 2023. Euro Surveill. 2024;29(23):2300616.  https://doi.org/10.2807/1560-7917.ES.2024.29.23.2300616  PMID: 38847120 
  24. Kondratiuk V, Jones BT, Kovalchuk V, Kovalenko I, Ganiuk V, Kondratiuk O, et al. Phenotypic and genotypic characterization of antibiotic resistance in military hospital-associated bacteria from war injuries in the Eastern Ukraine conflict between 2014 and 2020. J Hosp Infect. 2021;112:69-76.  https://doi.org/10.1016/j.jhin.2021.03.020  PMID: 33789157 
  25. Salmanov A, Shchehlov D, Svyrydiuk O, Bortnik I, Mamonova M, Korniyenko S, et al. Epidemiology of healthcare-associated infections and mechanisms of antimicrobial resistance of responsible pathogens in Ukraine: a multicentre study. J Hosp Infect. 2023;131:129-38.  https://doi.org/10.1016/j.jhin.2022.10.007  PMID: 36306892 
  26. Smit WL, Wunderink HF, Kluytmans JAJW, Tissing WJE, van Dijkhuizen EHP, Loeffen YGT, et al. Nosocomial transmission of NDM-1-containing Klebsiella pneumoniae ST147 in a Dutch pediatric oncology center associated with patients from Ukraine. BMC Infect Dis. 2024;24(1):1460.  https://doi.org/10.1186/s12879-024-10368-2  PMID: 39716112 
  27. Haller S, Kramer R, Becker K, Bohnert JA, Eckmanns T, Hans JB, et al. Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019. Euro Surveill. 2019;24(50):1900734.  https://doi.org/10.2807/1560-7917.ES.2019.24.50.1900734  PMID: 31847948 
  28. Gona F, Comandatore F, Battaglia S, Piazza A, Trovato A, Lorenzin G, et al. Comparison of core-genome MLST, coreSNP and PFGE methods for Klebsiella pneumoniae cluster analysis. Microb Genom. 2020;6(4):e000347.  https://doi.org/10.1099/mgen.0.000347  PMID: 32149598 
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