# In Vitro Activity of Novel β-Lactam/β-Lactamase Inhibitors Against Carbapenem-Resistant Pseudomonas aeruginosa and Enterobacterales in Korea

## TL;DR

This study assesses how well new antibiotic combinations work against drug-resistant bacteria in Korea, finding that some combinations are effective against certain types of resistant strains.

## Contribution

The study evaluates the in vitro effectiveness of novel β-lactam/β-lactamase inhibitors against carbapenem-resistant Pseudomonas aeruginosa and Enterobacterales in Korea.

## Key findings

- Ceftazidime/avibactam (CZA) showed high susceptibility rates against KPC-producing CRE isolates.
- Non-carbapenemase-producing CRE isolates had low susceptibility to ceftolozane/tazobactam (C/T) but high to CZA, IMR, and MEV.
- CRE infections were associated with higher in-hospital mortality compared to CRPA infections.

## Abstract

Background/Objectives: Carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are challenging multidrug-resistant pathogens. This study evaluated the in vitro susceptibility of CRE and CRPA blood isolates from Korea to novel β-lactam/β-lactamase inhibitor combinations: ceftolozane/tazobactam (C/T), ceftazidime/avibactam (CZA), imipenem/cilastatin/relebactam (IMR), and meropenem/vaborbactam (MEV). Methods: Blood isolates of CRE (n = 55) and CRPA (n = 65) collected between September 2017 and September 2022 in a Korean tertiary hospital were included. Carbapenemase production was determined using phenotypic and molecular methods. In vitro susceptibility to C/T, CZA, IMR, and MEV was determined primarily by broth microdilution using current CLSI/EUCAST breakpoints. Clinical characteristics and in-hospital mortality were retrospectively reviewed. Results: Among non-carbapenemase-producing (non-CP) CRPA isolates (n = 47), susceptibility rates were 83.0% to C/T and 70.2% to CZA. For KPC-producing CRE isolates (n = 28), susceptibility rates were high to CZA (92.9%), IMR (82.1%), and MEV (96.4%). However, non-CP CRE isolates (n = 22) showed low susceptibility to C/T (18.2%) but high susceptibility to CZA (100%), IMR (81.8%), and MEV (95.5%). CRE infections were associated with higher rates of hematologic malignancy, immunosuppression, and in-hospital mortality (63.6% vs. 18.5% for CRPA, p < 0.001). Conclusions: The susceptibility of CRE and CRPA to novel β-lactam/β-lactamase inhibitors varies significantly by species and carbapenemase production. CZA, IMR, and MEV showed promising activity against KPC-producing CRE. These findings can inform empirical therapy and stewardship efforts in Korea.