Abstract

Meropenem/Vaborbactam (MEM-VAB) is a novel carbapenem- β-lactamase inhibitor active against KPC-producing Enterobacteria. Herein, we evaluate the incidence of meropenem/vaborbactam-resistance among KPC-producing K. pneumoniae (KPC-Kp) bloodstream infection in a large Italian hospital. Meropenem/vaborbactam-resistance was found in 8% (n = 5) KPC-Kp, while 5% (n = 3) strains exhibited cross-resistance to ceftazidime/avibactam (CAZ-AVI). Genomic analysis revealed that meropenem/vaborbactam-resistance was associated with truncated OmpK35 and insertion of glycine and aspartic acid within OmpK36 at position 134–135 (GD134–135). Notably, no specific mutation was associated to cross-resistance. No specific antimicrobial treatment was related to favorable clinical outcomes, while cross-resistance was not associated to higher clinical and/or microbiological failures. Our study indicated that resistance to meropenem/vaborbactam was due to porins mutations and is associated with reduced susceptibility to both ceftazidime/avibactam and carbapenems.

Highlights

  • The retrospective clinical data revealed that 45% (28/62) of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) bacteremic patients were hospitalized in intensive care units

  • We evaluated the activities of meropenem/vaborbactam against 62 KPCKp clinical strains collected from bacteremic patients during 2018

  • Our findings showed that resistance to meropenem/vaborbactam emerged in 13% of KPC-Kp strains isolated from bloodstream infection

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Management and treatment of patients with infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) is a daily challenge in clinical practice. The KPC carbapenemase is often carried out in microorganisms co-harboring different antimicrobial resistance determinants, conferring multiple multidrug resistant phenotypes. Most antimicrobial molecules exhibit poor in vitro activity against KPC-Kp, reducing treatments available [1]. Combination therapies, including high-dose meropenem, colistin, fosfomycin, tigecycline, and aminoglycosides, are widely used, with suboptimal results [2,3,4]

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