Activity of cefepime/enmetazobactam against highly multidrug-resistant bacterial isolates recovered from war-associated wounds in Ukraine
Boral, Jale LU
; Toft, Nora
LU
; Baybes, Alp Eren
LU
; Tellapragada, Chaitanya
; Nazarchuk, Oleksandr
; Fernandez, Celine
LU
; Giske, Christian
and Riesbeck, Kristian
LU
(2026)
In JAC - Antimicrobial Resistance
8(1).
p.1-5
- Abstract
- Background: Escalating resistance among Gram-negative pathogens limits β-lactam options. Cefepime/enmetazobactam combines a fourth-generation cephalosporin with a class A β-lactamase inhibitor. We evaluated its activity against multidrug, extensive and pandrug-resistant war-wound isolates from Ukraine.
Materials and methods: We tested 215 clinical samples (2022-2023) isolated from wounded patients in Ukraine by broth microdilution. Paired comparisons of cefepime monotherapy versus cefepime/enmetazobactam was done to evaluate enmetazobactam. Whole-genome sequencing (n = 83) identified β-lactamases, sequence types and outer-membrane protein alterations.
Results: Across Enterobacterales, resistance decreased from 60.5%... (More) - Background: Escalating resistance among Gram-negative pathogens limits β-lactam options. Cefepime/enmetazobactam combines a fourth-generation cephalosporin with a class A β-lactamase inhibitor. We evaluated its activity against multidrug, extensive and pandrug-resistant war-wound isolates from Ukraine.
Materials and methods: We tested 215 clinical samples (2022-2023) isolated from wounded patients in Ukraine by broth microdilution. Paired comparisons of cefepime monotherapy versus cefepime/enmetazobactam was done to evaluate enmetazobactam. Whole-genome sequencing (n = 83) identified β-lactamases, sequence types and outer-membrane protein alterations.
Results: Across Enterobacterales, resistance decreased from 60.5% (26/43) with cefepime to 27.9% (12/43) with the cefepime/enmetazobactam combination. In K. pneumoniae, resistance declined from 92.6% (75/81) to 74% (60/81) and in P. mirabilis, from 88.9% (8/9) to 11.1% (1/9), respectively. P. aeruginosa showed a modest change [77.8% (23/36) to 58.3% (32/36)], while A. baumannii remained non-susceptible to both cefepime and cefepime/enmetazobactam with the rates of 91.3% (42/46) to 82.6% (36/46), respectively. Genotype-phenotype correlation revealed that in K. pneumoniae, reduced activity was associated with OmpK36 loop-3 insertions, OmpK35 loss and metallo-β-lactamases, whereas selected sequence types lacking these changes were more susceptible. In A. baumannii, OXA-type carbapenemases and blaADC beta-lactamases predominated; isolates lacking type VI secretion, omp33-36 and adhesin genes (ata/bap) demonstrated relatively higher susceptibility to cefepime/enmetazobactam.
Conclusions: Cefepime/enmetazobactam improved susceptibility relative to cefepime, most notably in Enterobacterales, but activity was constrained by permeability defects and non-target β-lactamases. Combination therapy with agents that does not get hydrolysed by MBLs and integrated β-lactamase detection with practical permeability indicators may optimize the clinical use of this combination in high-resistance settings. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/f5770f42-b51e-4d26-8257-2034492a8253
- author
- Boral, Jale
LU
; Toft, Nora
LU
; Baybes, Alp Eren
LU
; Tellapragada, Chaitanya
; Nazarchuk, Oleksandr
; Fernandez, Celine
LU
; Giske, Christian
and Riesbeck, Kristian
LU
- organization
- publishing date
- 2026
- type
- Contribution to journal
- publication status
- published
- subject
- in
- JAC - Antimicrobial Resistance
- volume
- 8
- issue
- 1
- article number
- dlaf256
- pages
- 1 - 5
- publisher
- Oxford University Press
- external identifiers
-
- pmid:41573238
- scopus:105028304669
- ISSN
- 2632-1823
- DOI
- 10.1093/jacamr/dlaf256
- language
- English
- LU publication?
- yes
- id
- f5770f42-b51e-4d26-8257-2034492a8253
- date added to LUP
- 2026-02-17 15:02:21
- date last changed
- 2026-02-18 07:33:19
@article{f5770f42-b51e-4d26-8257-2034492a8253,
abstract = {{Background: Escalating resistance among Gram-negative pathogens limits β-lactam options. Cefepime/enmetazobactam combines a fourth-generation cephalosporin with a class A β-lactamase inhibitor. We evaluated its activity against multidrug, extensive and pandrug-resistant war-wound isolates from Ukraine.<br/><br/>Materials and methods: We tested 215 clinical samples (2022-2023) isolated from wounded patients in Ukraine by broth microdilution. Paired comparisons of cefepime monotherapy versus cefepime/enmetazobactam was done to evaluate enmetazobactam. Whole-genome sequencing (n = 83) identified β-lactamases, sequence types and outer-membrane protein alterations.<br/><br/>Results: Across Enterobacterales, resistance decreased from 60.5% (26/43) with cefepime to 27.9% (12/43) with the cefepime/enmetazobactam combination. In K. pneumoniae, resistance declined from 92.6% (75/81) to 74% (60/81) and in P. mirabilis, from 88.9% (8/9) to 11.1% (1/9), respectively. P. aeruginosa showed a modest change [77.8% (23/36) to 58.3% (32/36)], while A. baumannii remained non-susceptible to both cefepime and cefepime/enmetazobactam with the rates of 91.3% (42/46) to 82.6% (36/46), respectively. Genotype-phenotype correlation revealed that in K. pneumoniae, reduced activity was associated with OmpK36 loop-3 insertions, OmpK35 loss and metallo-β-lactamases, whereas selected sequence types lacking these changes were more susceptible. In A. baumannii, OXA-type carbapenemases and blaADC beta-lactamases predominated; isolates lacking type VI secretion, omp33-36 and adhesin genes (ata/bap) demonstrated relatively higher susceptibility to cefepime/enmetazobactam.<br/><br/>Conclusions: Cefepime/enmetazobactam improved susceptibility relative to cefepime, most notably in Enterobacterales, but activity was constrained by permeability defects and non-target β-lactamases. Combination therapy with agents that does not get hydrolysed by MBLs and integrated β-lactamase detection with practical permeability indicators may optimize the clinical use of this combination in high-resistance settings.}},
author = {{Boral, Jale and Toft, Nora and Baybes, Alp Eren and Tellapragada, Chaitanya and Nazarchuk, Oleksandr and Fernandez, Celine and Giske, Christian and Riesbeck, Kristian}},
issn = {{2632-1823}},
language = {{eng}},
number = {{1}},
pages = {{1--5}},
publisher = {{Oxford University Press}},
series = {{JAC - Antimicrobial Resistance}},
title = {{Activity of cefepime/enmetazobactam against highly multidrug-resistant bacterial isolates recovered from war-associated wounds in Ukraine}},
url = {{http://dx.doi.org/10.1093/jacamr/dlaf256}},
doi = {{10.1093/jacamr/dlaf256}},
volume = {{8}},
year = {{2026}},
}