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

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.

Automated summary

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.