Ceftazidime-avibactam resistance and restoration of carbapenem susceptibility in KPC-producing Klebsiella pneumoniae infections: A case series

Abstract

Objectives: Since the introduction of the β-lactam/β-lactamase inhibitor ceftazidime-avibactam (CZA), rapid evolution of resistance has been reported in different KPC-producing Klebsiella pneumoniae isolates. In this multicenter retrospective study, we describe the emergence of CZA resistance and evaluate the mutations that might be responsible for the restoration of carbapenem susceptibility.

Methods: During a study period of 18 months, KPC-producing K. pneumoniae isolates of five hospitalized patients were collected with phenotypic development of CZA resistance.

Results: In vitro restoration of carbapenem susceptibility during treatment was observed in 3 isolates. Whole genome sequencing of these isolates showed a D179Y mutation in the KPC gene of 2 variants and a KPC-2 with a Δ242-GT-243 deletion (KPC-14). Two KPC-3 variants showed CZA resistance with sustained carbapenemase activity without genomic adaptations in the KPC gene.

Conclusions: This study confirms the emergence of CZA resistance in KPC K. pneumoniae. The role of carbapenems in treating patients with these variants is unclear and combination therapies warrant further investigation.

Keywords: Ceftazidime-avibactam resistance; KPC mutations; Klebsiella pneumoniae carbapenemase.