Carbapenem-resistant Klebsiella pneumoniae: the role of plasmids in emergence, dissemination, and evolution of a major clinical challenge

ABSTRACT

Introduction

Klebsiella pneumoniae is a major agent of healthcare-associated infections and a cause of some community-acquired infections, including severe bacteremic infections associated with metastatic abscesses in liver and other organs. Clinical relevance is compounded by its outstanding propensity to evolve antibiotic resistance. In particular, the emergence and dissemination of carbapenem resistance in K. pneumoniae has posed a major challenge due to the few residual treatment options, which have only recently been expanded by some new agents. The epidemiological success of carbapenem-resistant K. pneumoniae (CR-Kp) is mainly linked with clonal lineages that produce carbapenem-hydrolyzing enzymes (carbapenemases) encoded by plasmids.

Areas covered

Here, we provide an updated overview on the mechanisms underlying the emergence and dissemination of CR-Kp, focusing on the role that plasmids have played in this phenomenon and in the co-evolution of resistance and virulence in K. pneumoniae.

Expert opinion

CR-Kp have disseminated on a global scale, representing one of the most important contemporary public health issues. These strains are almost invariably associated with complex multi-drug resistance (MDR) phenotypes, which can also include recently approved antibiotics. The heterogeneity of the molecular bases responsible for these phenotypes poses significant hurdles for therapeutic and diagnostic purposes.

KEYWORDS:

• Klebsiella pneumoniae
• carbapenem resistance
• carbapenemase-encoding plasmids
• mobile genetic elements
• virulence
• high-risk clones

Article highlights

• Klebsiella pneumoniae is a highly versatile pathogen, playing a primary role in opportunistic healthcare-associated infections, and being relevant also in some community-acquired infections.

• K. pneumoniae exhibits high propensity to develop resistance to antibiotics, including carbapenems, and carbapenem-resistant K. pneumoniae (CR-Kp) contribute for the majority of carbapenem-resistant Enterobacterales globally.

• In CR-Kp, resistance to carbapenems is mostly due to acquisition of plasmids encoding carbapenemases of different types and, often, additional resistance determinants.

• Highly diverse carbapenemase-encoding plasmids have evolved, contributing to successful dissemination of carbapenem resistance among some high-risk clonal lineages of K. pneumoniae.

• Recombination events involving plasmids and/or associated mobile genetic elements can contribute to accretion of resistance determinants and expansion of the resistance phenotype.

• Plasticity of plasmids and cognate mobile genetic elements can also modulate resistance via alteration of the gene dosage, affecting resistance to some novel β-lactamase inhibitor combinations.

• Convergence in a single isolate of resistance and virulence plasmids, or of hybrid derivatives thereof, can promote the emergence of carbapenem-resistant and highly virulent pathotypes of K. pneumoniae, representing a worrisome clinical evolution.

Declaration of interest

Outside the submitted work, VDP reports speakers’ bureaus from Ada. Outside the submitted work, GMR reports grants or contracts from Ada, Alifax, Angelini, Arrow Diagnostics, Biomedical Service, bioMérieux, Cepheid, Hain Lifescience GmbH, Menarini, Meridian, MSD, Nordic Pharma, Qlinea, Quantamatrix, Quidel, Qvella, SD Biosensor, Seegene, Shionogi, Symcel; consulting fees from bioMérieux, MSD; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events by bioMérieux, Menarini, MSD, Pfizer, Shionogi, Relab. Outside the submitted work, MMD reports contracts from Glaxo-Smith Kline and payments for software consultancy and congresses attendance by Arrow Diagnostics. Outside the submitted work, SP reports contracts from Molteni Therapeutics and congresses attendance by Arrow Diagnostics.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14787210.2024.2305854

Additional information

Funding

This work was partially supported by a research grant (RF-2016-02364584) by the Italian Ministry of Health to GMR and by the research grant financed by the European Union – Next Generation EU - PRIN 2022 (20224T3X8K) by the Italian Ministry of Education, University and Research to MMD.