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Objectives <p>KPC-producing <i>Klebsiella pneumoniae</i> (KPC-KP) are increasingly prevalent in Europe, largely due to the dissemination of a combination of successful plasmids and clones. The aim of this study was to characterise, both phenotypically and genotypically - with a focus on cefiderocol resistance - the KPC-KP isolates submitted to the Swiss National Reference Centre for Emerging Antibiotic Resistance (NARA), from February 2024 to February 2025.</p> Methods <p>Sixty-six non-duplicate KPC-KP isolates were submitted to NARA over the study period from across Switzerland. Antimicrobial susceptibility was determined using a combination of disk testing, E-tests and broth microdilution, and interpreted according to EUCAST methodology. Whole-genome sequencing (WGS) was performed on all isolates to allow for further characterisation. WGS analyses and assemblies were performed using the IMMense pipeline. KPC variants were cloned into vector pUCP24 and transformed into <i>Escherichia coli</i> Top10.</p> Results <p>The most prevalent KPC variants identified in this study were KPC-3 (<i>n</i> = 49), KPC-2 (<i>n</i> = 13), KPC-184 (<i>n</i> = 2), KPC-39 (<i>n</i> = 1), and one isolate harboured a novel KPC allele, designated KPC-272. Within the 66 isolates, 24 sequence types (STs) were ascertained, represented by one to three isolates with the exceptions of ST307 (<i>n</i> = 14), ST512 (<i>n</i> = 8), and ST258 (<i>n</i> = 7), ST39 (<i>n</i> = 5) and ST101 (<i>n</i> = 5). All isolates exhibited resistance to cephalosporins and carbapenems and, notably, 18 isolates (27.3%) were cefiderocol (FDC) -resistant. Analysis of WGS data for potential mechanisms of FDC resistance identified that 15/18 isolates harboured a plasmid-mediated <i>fec</i> operon, and 4/18 isolates carried expanded-spectrum beta-lactamases that have been reported to contribute to FDC resistance.</p> Conclusions <p>This study determined that the current dissemination of KPC-KP isolates in Switzerland is polyclonal and not related to a single predominant and “successful” clone. The elevated rate of resistance to the “last resort” antimicrobial, FDC, is concerning, and was shown to be caused by multifactorial mechanisms.</p>

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KPC-producing Klebsiella pneumoniae in Switzerland from 2024 to 2025: comparative genomics and cefiderocol resistance mechanisms analyses

  • 期刊论文

  • 发表日期：

    2026年4月17日

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  • Jacqueline Findlay,
  • Patrice Nordmann,
  • R Lienhard,
  • L Vonallmen,
  • C Schilt,
  • A Scherler,
  • K Lucke,
  • M Jutzi,
  • M Reichmuth,
  • U Schibli,
  • C Fricker,
  • S Pranghofer,
  • D Blanc,
  • A Vitale,
  • B Lemaire,
  • M Fatoux,
  • M Tritten,
  • L Rumebe,
  • N Liassine,
  • G Jost,
  • N Wohlwend,
  • D Schultze,
  • K Burren,
  • A Westers,
  • M Imperiali,
  • L Pozzi,
  • D Balzari,
  • G Vaninetti,
  • C Cirillo,
  • V Gaia,
  • E Pianezzi,
  • G Martinetti Lucchini,
  • F Baggi Menozzi,
  • A Jayol,
  • C Guyon,
  • D Hyden,
  • M Maitrejean,
  • V Deggi-Messmer,
  • D Bandeira,
  • C Fournier,
  • S Pfister,
  • C Nusbaumer,
  • L Bertaiola Monnerat,
  • J Schrenzel,
  • G Renzi,
  • A Cherkaoui,
  • D Andrey,
  • S Emonet,
  • M Eyer,
  • R Maret,
  • A Belo,
  • D Mabillard,
  • M Moraz,
  • K Herzog,
  • V Gisler,
  • E Hitz,
  • M Oberle,
  • C Castelberg,
  • H Fankhauser,
  • S Graf,
  • N Dubey,
  • C Guler,
  • M Schoenenberger,
  • U Karrer,
  • F Piran,
  • C Andreutti,
  • M Dessauges,
  • T Schmid,
  • B Suterbuser,
  • I Mitrovic,
  • V Bruderer,
  • P Staehli,
  • B Schnell,
  • C O Marti,
  • I Steffen,
  • A Imhof,
  • B Preiswerk,
  • V Dilorenzo,
  • C Payen,
  • D Boschung,
  • L Comte,
  • M Schacher,
  • M Brandenberger,
  • C Zowa,
  • C Zehnder,
  • B Mathis,
  • L Basilico,
  • G Togni,
  • P Minkova,
  • Y Born,
  • M Kuegler,
  • V Povolo,
  • S Droz,
  • M Elzi,
  • C Casanova,
  • C Lang,
  • A Blaich,
  • S Schmid,
  • B Ivan,
  • S Mancini,
  • O Dubois,
  • K Narr,
  • S Schoch,
  • S Ellenberger,
  • S Seiffert,
  • Helena M B Seth-Smith,
  • Adrian Egli,
  • Laurent Poirel

摘要

Objectives

KPC-producing Klebsiella pneumoniae (KPC-KP) are increasingly prevalent in Europe, largely due to the dissemination of a combination of successful plasmids and clones. The aim of this study was to characterise, both phenotypically and genotypically - with a focus on cefiderocol resistance - the KPC-KP isolates submitted to the Swiss National Reference Centre for Emerging Antibiotic Resistance (NARA), from February 2024 to February 2025.

Methods

Sixty-six non-duplicate KPC-KP isolates were submitted to NARA over the study period from across Switzerland. Antimicrobial susceptibility was determined using a combination of disk testing, E-tests and broth microdilution, and interpreted according to EUCAST methodology. Whole-genome sequencing (WGS) was performed on all isolates to allow for further characterisation. WGS analyses and assemblies were performed using the IMMense pipeline. KPC variants were cloned into vector pUCP24 and transformed into Escherichia coli Top10.

Results

The most prevalent KPC variants identified in this study were KPC-3 (n = 49), KPC-2 (n = 13), KPC-184 (n = 2), KPC-39 (n = 1), and one isolate harboured a novel KPC allele, designated KPC-272. Within the 66 isolates, 24 sequence types (STs) were ascertained, represented by one to three isolates with the exceptions of ST307 (n = 14), ST512 (n = 8), and ST258 (n = 7), ST39 (n = 5) and ST101 (n = 5). All isolates exhibited resistance to cephalosporins and carbapenems and, notably, 18 isolates (27.3%) were cefiderocol (FDC) -resistant. Analysis of WGS data for potential mechanisms of FDC resistance identified that 15/18 isolates harboured a plasmid-mediated fec operon, and 4/18 isolates carried expanded-spectrum beta-lactamases that have been reported to contribute to FDC resistance.

Conclusions

This study determined that the current dissemination of KPC-KP isolates in Switzerland is polyclonal and not related to a single predominant and “successful” clone. The elevated rate of resistance to the “last resort” antimicrobial, FDC, is concerning, and was shown to be caused by multifactorial mechanisms.