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

<b>Background/Objectives:</b> Carbapenem-resistant <i>Enterobacterales</i> (CRE) and carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CRPA) are challenging multidrug-resistant pathogens. This study evaluated the in vitro susceptibility of CRE and CRPA blood iso...

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Main Authors: Seulgi Moon, Jongyoun Yi, Mee Kyung Ko, Yong Ki Sim, Kye-Hyung Kim
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/7/649
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author Seulgi Moon
Jongyoun Yi
Mee Kyung Ko
Yong Ki Sim
Kye-Hyung Kim
author_facet Seulgi Moon
Jongyoun Yi
Mee Kyung Ko
Yong Ki Sim
Kye-Hyung Kim
author_sort Seulgi Moon
collection DOAJ
description <b>Background/Objectives:</b> Carbapenem-resistant <i>Enterobacterales</i> (CRE) and carbapenem-resistant <i>Pseudomonas aeruginosa</i> (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). <b>Methods:</b> Blood isolates of CRE (<i>n</i> = 55) and CRPA (<i>n</i> = 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. <b>Results:</b> Among non-carbapenemase-producing (non-CP) CRPA isolates (<i>n</i> = 47), susceptibility rates were 83.0% to C/T and 70.2% to CZA. For KPC-producing CRE isolates (<i>n</i> = 28), susceptibility rates were high to CZA (92.9%), IMR (82.1%), and MEV (96.4%). However, non-CP CRE isolates (<i>n</i> = 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, <i>p</i> < 0.001). <b>Conclusions:</b> 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.
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spelling doaj-art-3624de1f2c2e4b1888a62011f8c020ec2025-08-20T03:13:41ZengMDPI AGAntibiotics2079-63822025-06-0114764910.3390/antibiotics14070649In Vitro Activity of Novel β-Lactam/β-Lactamase Inhibitors Against Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> and <i>Enterobacterales</i> in KoreaSeulgi Moon0Jongyoun Yi1Mee Kyung Ko2Yong Ki Sim3Kye-Hyung Kim4Department of Laboratory Medicine, Pusan National University School of Medicine, Busan 49241, Republic of KoreaDepartment of Laboratory Medicine, Pusan National University School of Medicine, Busan 49241, Republic of KoreaBiomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of KoreaDepartment of Internal Medicine, Pusan National University School of Medicine, Busan 49241, Republic of KoreaBiomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea<b>Background/Objectives:</b> Carbapenem-resistant <i>Enterobacterales</i> (CRE) and carbapenem-resistant <i>Pseudomonas aeruginosa</i> (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). <b>Methods:</b> Blood isolates of CRE (<i>n</i> = 55) and CRPA (<i>n</i> = 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. <b>Results:</b> Among non-carbapenemase-producing (non-CP) CRPA isolates (<i>n</i> = 47), susceptibility rates were 83.0% to C/T and 70.2% to CZA. For KPC-producing CRE isolates (<i>n</i> = 28), susceptibility rates were high to CZA (92.9%), IMR (82.1%), and MEV (96.4%). However, non-CP CRE isolates (<i>n</i> = 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, <i>p</i> < 0.001). <b>Conclusions:</b> 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.https://www.mdpi.com/2079-6382/14/7/649antimicrobial agentscarbapenem resistancebacteremiaβ-lactamase inhibitorsKoreasusceptibility
spellingShingle Seulgi Moon
Jongyoun Yi
Mee Kyung Ko
Yong Ki Sim
Kye-Hyung Kim
In Vitro Activity of Novel β-Lactam/β-Lactamase Inhibitors Against Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> and <i>Enterobacterales</i> in Korea
Antibiotics
antimicrobial agents
carbapenem resistance
bacteremia
β-lactamase inhibitors
Korea
susceptibility
title In Vitro Activity of Novel β-Lactam/β-Lactamase Inhibitors Against Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> and <i>Enterobacterales</i> in Korea
title_full In Vitro Activity of Novel β-Lactam/β-Lactamase Inhibitors Against Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> and <i>Enterobacterales</i> in Korea
title_fullStr In Vitro Activity of Novel β-Lactam/β-Lactamase Inhibitors Against Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> and <i>Enterobacterales</i> in Korea
title_full_unstemmed In Vitro Activity of Novel β-Lactam/β-Lactamase Inhibitors Against Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> and <i>Enterobacterales</i> in Korea
title_short In Vitro Activity of Novel β-Lactam/β-Lactamase Inhibitors Against Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> and <i>Enterobacterales</i> in Korea
title_sort in vitro activity of novel β lactam β lactamase inhibitors against carbapenem resistant i pseudomonas aeruginosa i and i enterobacterales i in korea
topic antimicrobial agents
carbapenem resistance
bacteremia
β-lactamase inhibitors
Korea
susceptibility
url https://www.mdpi.com/2079-6382/14/7/649
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