# KPC-33 and ompK37 mutations: Unraveling the mechanism of ceftazidime/avibactam resistance in ST11 carbapenem-resistant Klebsiella pneumoniae

## TL;DR

This study identifies genetic changes in a type of antibiotic-resistant bacteria that help it resist a specific drug combination, highlighting the importance of genomic monitoring.

## Contribution

The study reveals a novel resistance mechanism involving blaKPC-33 and ompK37 mutations in ST11 CRKP.

## Key findings

- The isolate showed high-level resistance to ceftazidime-avibactam and carbapenems.
- Resistance was linked to blaKPC-33 and mutations in the ompK37 gene.
- The isolate remained susceptible to tigecycline, polymyxin B, and amikacin.

## Abstract

Global surveillance indicates rising ceftazidime-avibactam resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP), with sequence type 11 predominating in China. The contribution of blaKPC variants and porin alterations to high-level resistance remains significant.

We employed whole-genome sequencing and functional analyses to characterise a CZA-resistant ST11 CRKP isolate recovered from a patient without prior exposure to ceftazidime-avibactam or carbapenems.

The isolate harboured blaKPC-33 on a non-conjugative plasmid and multiple non-synonymous mutations in the porin gene ompK37, concomitant with high-level resistance to ceftazidime-avibactam and carbapenems while retaining susceptibility to tigecycline, polymyxin B and amikacin.

blaKPC-33 coupled with OmpK37 alterations underpins dual resistance to ceftazidime-avibactam and carbapenems in ST11 CRKP, underscoring the need for genomic surveillance and rapid detection of this resistance mechanism.