. 2022 Sep 21;11(10):1286.

doi: 10.3390/antibiotics11101286.

Surveillance and Genomic Analysis of Third-Generation Cephalosporin-Resistant and Carbapenem-Resistant Klebsiella pneumoniae Complex in Germany

Kyriaki Xanthopoulou^{1

2}, Can Imirzalioglu^{1

3}, Sarah V Walker^{1

2}, Michael Behnke^{1

4

5}, Ariane G Dinkelacker^{1

6}, Simone Eisenbeis^{1

7}, Petra Gastmeier^{1

4

5}, Hanna Gölz^{1

8}, Nadja Käding^{1

9}, Winfried V Kern¹⁰, Axel Kola^{1

4

5}, Evelyn Kramme^{1

9}, Kai Lucassen², Alexander Mischnik^{1

9

10}, Silke Peter^{1

6}, Anna M Rohde^{1

4}, Jan Rupp^{1

9}, Evelina Tacconelli^{1

7}, David Tobys^{1

2}, Maria J G T Vehreschild^{1

11

12}, Julia Wille^{1

2}, Harald Seifert^{1

2}, Paul G Higgins^{1

2}; DZIF R-Net Study Group

Collaborators, Affiliations

Collaborators

DZIF R-Net Study Group:
Lena Biehl, Trinad Chakraborty, Nadine Hoffmann, Florian Hölzl, Baris Bader, Michael Buhl, Frieder Fuchs, Georg Häcker, Nathalie Jazmati, Dana Lenke, Luis Alberto Peña Diaz, Gabriele Peyerl-Hoffmann, Georg Pilarski, Susanna Proske, Sabine Schuster, Norbert Thoma, Martina Vavra, Anna Weber

Affiliations

¹ German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany.
² Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50935 Cologne, Germany.
³ Institute of Medical Microbiology, Justus Liebig University Giessen, 35392 Giessen, Germany.
⁴ Institute of Hygiene and Environmental Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 12203 Berlin, Germany.
⁵ National Reference Centre for the Surveillance of Nosocomial Infections, 12203 Berlin, Germany.
⁶ Institute of Medical Microbiology and Hygiene, University Hospital Tübingen, 72074 Tübingen, Germany.
⁷ Division of Infectious Diseases, Department of Internal Medicine I, University Hospital Tübingen, 72076 Tübingen, Germany.
⁸ Institute for Medical Microbiology and Hygiene, University Medical Centre Freiburg, 79104 Freiburg, Germany.
⁹ Department of Infectious Diseases and Microbiology, University of Lübeck and University Hospital Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany.
¹⁰ Division of Infectious Diseases, Department of Medicine II, Faculty of Medicine, Medical Centre, University of Freiburg, 79106 Freiburg, Germany.
¹¹ Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany.
¹² Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany.

PMID: 36289942
PMCID: PMC9598256
DOI: 10.3390/antibiotics11101286

Surveillance and Genomic Analysis of Third-Generation Cephalosporin-Resistant and Carbapenem-Resistant Klebsiella pneumoniae Complex in Germany

Kyriaki Xanthopoulou et al. Antibiotics (Basel). 2022.

. 2022 Sep 21;11(10):1286.

doi: 10.3390/antibiotics11101286.

Authors

Collaborators

DZIF R-Net Study Group:
Lena Biehl, Trinad Chakraborty, Nadine Hoffmann, Florian Hölzl, Baris Bader, Michael Buhl, Frieder Fuchs, Georg Häcker, Nathalie Jazmati, Dana Lenke, Luis Alberto Peña Diaz, Gabriele Peyerl-Hoffmann, Georg Pilarski, Susanna Proske, Sabine Schuster, Norbert Thoma, Martina Vavra, Anna Weber

Affiliations

¹ German Centre for Infection Research (DZIF), 38124 Braunschweig, Germany.
² Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50935 Cologne, Germany.
³ Institute of Medical Microbiology, Justus Liebig University Giessen, 35392 Giessen, Germany.
⁴ Institute of Hygiene and Environmental Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 12203 Berlin, Germany.
⁵ National Reference Centre for the Surveillance of Nosocomial Infections, 12203 Berlin, Germany.
⁶ Institute of Medical Microbiology and Hygiene, University Hospital Tübingen, 72074 Tübingen, Germany.
⁷ Division of Infectious Diseases, Department of Internal Medicine I, University Hospital Tübingen, 72076 Tübingen, Germany.
⁸ Institute for Medical Microbiology and Hygiene, University Medical Centre Freiburg, 79104 Freiburg, Germany.
⁹ Department of Infectious Diseases and Microbiology, University of Lübeck and University Hospital Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany.
¹⁰ Division of Infectious Diseases, Department of Medicine II, Faculty of Medicine, Medical Centre, University of Freiburg, 79106 Freiburg, Germany.
¹¹ Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany.
¹² Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany.

PMID: 36289942
PMCID: PMC9598256
DOI: 10.3390/antibiotics11101286

Abstract

To analyse the epidemiology and population structure of third-generation cephalosporin-resistant (3GCR) and carbapenem-resistant (CR) Klebsiella pneumoniae complex isolates, patients were screened for rectal colonisation with 3GCR/CR K. pneumoniae complex on admission to six German university hospitals (2016-2019). Also collected were 3GCR/CR and susceptible K. pneumoniae isolates from patients with bloodstream infections (2016-2018). Whole-genome sequencing was performed followed by multilocus sequencing typing (MLST), core-genome MLST, and resistome and virulome analysis. The admission prevalence of 3GCR K. pneumoniae complex isolates during the 4-year study period was 0.8%, and 1.0 bloodstream infection per 1000 patient admissions was caused by K. pneumoniae complex (3GCR prevalence, 15.1%). A total of seven K. pneumoniae complex bloodstream isolates were CR (0.8%). The majority of colonising and bloodstream 3GCR isolates were identified as K. pneumoniae, 96.7% and 98.8%, respectively; the remainder were K. variicola and K. quasipneumoniae. cgMLST showed a polyclonal population of colonising and bloodstream isolates, which was also reflected by MLST and virulome analysis. CTX-M-15 was the most prevalent extended-spectrum beta-lactamase, and 29.7% of the colonising and 48.8% of the bloodstream isolates were high-risk clones. The present study provides an insight into the polyclonal 3GCR K. pneumoniae population in German hospitals.

Keywords: Klebsiella pneumoniae complex; bloodstream infections; carbapenem resistance; colonisation; third-generation cephalosporin resistance; typing.

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Conflict of interest statement

C.I. has served as a consultant to MSD Sharp and Dohme and Shionogi and has received lecture fees from MSD Sharp and Dohme. S.P. consulted for IDbyDNA and received speaker&rsquo;s honoraria from bioM&eacute;rieux. MJGTV received research grants from 3M, Astellas Pharma, Biontech, DaVolterra, Evonik, Gilead Sciences, Glycom, Immunic, MaaT Pharma, Merck/MSD, Organobalance, Seres Therapeutics, and Takeda Pharmaceutical and speaker fees or consultation fees from Alb Fils Kliniken GmbH, Arderypharm, Astellas Pharma, Basilea, bioM&eacute;rieux, DaVolterra, Farmak International Holding GmbH, Ferring, Gilead Sciences, Immunic AG, MaaT Pharma, Merck/MSD, Pfizer, Roche, Organobalance, and SocraTec R&D GmbH. The remaining authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

**Figure 1**
(A) Prevalence of 3GCR *K. pneumoniae* complex carriage of patients on hospital admission. (B) Prevalence of 3GCR among 880 *K. pneumoniae* complex bloodstream isolates.

**Figure 2**
Dendrogram generated using Ridom SeqSphere+ for the HiR 3GCR/CR colonising *K. pneumoniae* complex isolates (n = 27) coloured by study centre and identified by ST type, ignoring missing values. Each box represents one isolate from an individual patient according to sequence analysis of 2358 cgMLST target genes.

**Figure 3**
Dendrogram generated using Ridom SeqSphere+ for the HiR 3GCR/CR *K. pneumoniae* complex bloodstream isolates (n = 39) coloured by study centre and identified by ST type, ignoring missing values. Each box represents one isolate from an individual patient according to sequence analysis of 2358 cgMLST target genes.

**Figure 4**
Dendrogram generated using Ridom SeqSphere+ for the HiR 3GCS/CS *K. pneumoniae* complex bloodstream isolates (n = 15) coloured by study centre and identified by ST type, ignoring missing values. Each box represents one isolate from an individual patient according to sequence analysis of 2358 cgMLST target genes.

See this image and copyright information in PMC

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Surveillance and Genomic Analysis of Third-Generation Cephalosporin-Resistant and Carbapenem-Resistant Klebsiella pneumoniae Complex in Germany

Collaborators

Affiliations

Surveillance and Genomic Analysis of Third-Generation Cephalosporin-Resistant and Carbapenem-Resistant Klebsiella pneumoniae Complex in Germany

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources