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
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Funding
- Assistance Publique-Hopitaux de Paris
- University Paris-Saclay
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT), through the French National Research Agency [ANR-10-LABX-33]
- 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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