4.7 Article

KPC-39-Mediated Resistance to Ceftazidime-Avibactam in a Klebsiella pneumoniae ST307 Clinical Isolate

Journal

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 65, Issue 12, Pages -

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01160-21

Keywords

avibactam resistance; carbapenemase; KPC

Funding

  1. Assistance Publique-Hopitaux de Paris
  2. University Paris-Saclay
  3. Institut National de la Sante et de la Recherche Medicale (INSERM)
  4. Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), through the French National Research Agency [ANR-10-LABX-33]
  5. ANR-BMBF French-German bilateral project Natural-Arsenal (New Antibiotics Tackling mUlti-Resistance by acting on Alternative bacteriaL tARgets in Synergy with mEmbranedisruptiNg AntimicrobiaL peptides) [ANR-19-AMRB-0004]

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Resistance to the combination of ceftazidime (CAZ) and avibactam (AVI) is increasing, with a CAZ-AVI-resistant Klebsiella pneumoniae strain reported here. This strain, belonging to the high-risk sequence type 307 (ST307) clone, produces Klebsiella pneumoniae carbapenemase 39 (KPC-39), a single-amino-acid variant of KPC3. The study found that KPC-39 has lost carbapenemase activity but shows increased affinity for CAZ, suggesting potential silent dissemination in European healthcare settings.
Resistance to the ceftazidime (CAZ)-avibactam (AVI) combination is increasingly being reported. Here, we report a CAZ-AVI-resistant Klebsiella pneumoniae strain belonging to the high-risk sequence type 307 (ST307) clone and producing Klebsiella pneumoniae carbapenemase 39 (KPC-39), a single-amino-acid variant of KPC3 (A172T). Cloning experiments, steady-state kinetic parameters, and molecular dynamics simulations revealed a loss of carbapenemase activity and increased affinity for CAZ. KPC-39 was identified in a patient without prior exposure to CAZ-AVI, suggesting silent dissemination in European health care settings.

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