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. 2023 Dec;55(1):101-113.
doi: 10.1080/07853890.2022.2152484.

Treatment and diagnosis of severe KPC-producing Klebsiella pneumoniae infections: a perspective on what has changed over last decades

Daniele Roberto Giacobbe  1   2 , Vincenzo Di Pilato  3 , Ilias Karaiskos  4 , Tommaso Giani  5   6 , Anna Marchese  3   7 , Gian Maria Rossolini  5   6 , Matteo Bassetti  1   2
Affiliations

Treatment and diagnosis of severe KPC-producing Klebsiella pneumoniae infections: a perspective on what has changed over last decades

Daniele Roberto Giacobbe et al. Ann Med. 2023 Dec.

Abstract

Antimicrobial resistance is a global health threat. Among Gram-negative bacteria, resistance to carbapenems, a class of β-lactam antibiotics, is usually a proxy for difficult-to-treat resistance, since carbapenem-resistant organisms are often resistant to many classes of antibiotics. Carbapenem resistance in the Gram-negative pathogen Klebsiella pneumoniae is mostly due to the production of carbapenemases, enzymes able to hydrolyze carbapenems, and K. pneumoniae carbapenemase (KPC)-type enzymes are overall the most prevalent carbapenemases in K. pneumoniae. In the last decade, the management of severe infections due to KPC-producing K. pneumoniae (KPC-Kp) in humans has presented many peculiar challenges to clinicians worldwide. In this perspective, we discuss how the treatment of severe KPC-Kp infections has evolved over the last decades, guided by the accumulating evidence from clinical studies, and how recent advances in diagnostics have allowed to anticipate identification of KPC-Kp in infected patients.KEY MESSAGESIn the last decade, the management of severe infections due to KPC-Kp has presented many peculiar challenges to clinicians worldwideFollowing the introduction in clinical practice of novel β-lactam/β-lactamase inhibitor combinations and novel β-lactams active against KPC-producing bacteria, the management of severe KPC-Kp infections has witnessed a remarkable evolutionTreatment of severe KPC-Kp infections is a highly dynamic process, in which the wise use of novel antimicrobials should be accompanied by a continuous refinement based on evolving clinical evidence and laboratory diagnostics.

Keywords: imipenem-relebactam; BL-BLI; KPC; cefiderocol; ceftazidime-avibactam; early diagnosis; meropenem-vaborbactam; rapid tests.

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Conflict of interest statement

Outside the submitted work, DRG reports investigator-initiated grants from Pfizer, Shionogi, and Gilead Italia, and advisor/consultant and/or speaker’s bureau from Pfizer and Tillotts Pharma. Outside the submitted work, AM reports investigator-initiated grants from Gilead Italia. Outside the submitted work, VDP reports research grants from Seegene. Outside the submitted work, TG reports advisor/consultant and/or speaker’s bureau and/or research grants and/or personal fees from Alifax, bioMérieux, Thermo Fisher Scientific, Seegene, Accelerate Diagnostics, Merlin, VenatorX, and AstraZeneca. Outside the submitted work, GMR reports advisor/consultant and/or speaker’s bureau and/or research grants and/or personal fees from Accelerate, Angelini, Arrow, Becton Dickinson, Biomedical Service, bioMérieux, Cepheid, DID, Hain Lifescience GmbH, Menarini, Meridian, MSD, Nordic Pharma, Pfizer, Qiagen, Qlinea, Qpex, Quidel, Qvella, Roche, SD Biosensor, Seegene, Setlance, Shionogi, Symcel, Thermo Fisher, VenatorX, Zambon. Outside the submitted work, MB reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Bayer, BioMérieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, and Shionogi.

Figures

Figure 1.
Figure 1.
Combination therapies frequently employed before availability of novel β-lactam/β-lactam inhibitor (BL/BLI) combinations and β-lactams (BL) for the treatment of severe infections caused by KPC-producing Klebsiella pneumoniae. CNS: central nervous system; KPC-Kp: Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae; MIC: minimum inhibitory concentration; PK/PD: pharmacokinetic/pharmacodynamic. Information included in the table is from Refs. [9,15,19–34].
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