Molecular characterization of carbapenemase-producing Enterobacterales from Peshawar City, Khyber Pakhtunkhwa, Pakistan.
- 1Institute of Medical Microbiology, University Zurich, Gloriastrasse 28/30, Zurich 8006, Switzerland.
- 2Department of Microbiology, The University of Haripur, Haripur, Pakistan.
- 3SIB Swiss Institute of Bioinformatics, Zurich, Switzerland.
Abstract
Background/objectives
The dissemination of multidrug-resistant Enterobacterales poses a critical public health challenge, particularly in resource-limited regions with high antimicrobial use and limited surveillance. We analysed the phenotypic and genotypic resistance profiles of carbapenemase-producing Enterobacterales collected in 2023 from three tertiary care hospitals in Peshawar, Pakistan.Methods
We performed antimicrobial susceptibility testing on 32 Enterobacterales isolates suspected of carbapenemase production using disk diffusion, gradient diffusion, and broth microdilution according to EUCAST guidelines. We conducted whole-genome sequencing to identify resistance genes, sequence types, and mutations associated with reduced susceptibility to novel β-lactams.Results
The collection comprised 16 Escherichia coli, 13 Klebsiella pneumoniae, and 3 Proteus mirabilis isolates. The predominant carbapenemase gene was bla NDM-5 (90.6%), frequently combined with bla OXA-48-like variants (46.9%). ESBL genes, mainly bla CTX-M-15, were common (78.1%), while CMY-type AmpC β-lactamases were detected in 28.1% of isolates. Insertions in the PBP3-encoding gene ftsI and CMY co-production were associated with elevated aztreonam-avibactam MICs in E.coli. Reduced cefiderocol susceptibility was observed mainly among NDM-producing E. coli ST2 isolates carrying cirA disruption and ftsI insertions. All isolates remained susceptible to colistin, most of them to gentamicin (84.4%), and exhibited wild-type MIC-distributions for tigecycline, and eravacycline. Genomic analysis identified clustering of high-risk clones, suggesting ongoing local transmission. Notably, 11/13 K. pneumoniae ST147 isolates carried multiple virulence-associated genes consistent with hypervirulence.Conclusions
High-risk NDM-producing Enterobacterales with increasingly complex resistance and virulence mechanisms are circulating in Pakistan, including determinants compromising last-line β-lactams. Strengthened genomic surveillance is essential to guide therapy and limit further spread.
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BibTeX
@article{mancini2026molecular,
title = {{Molecular characterization of carbapenemase-producing Enterobacterales from Peshawar City, Khyber Pakhtunkhwa, Pakistan.}},
author = {Stefano Mancini and Irfan Ullah and Helena M B Seth-Smith and Natalia Kolesnik-Goldmann and Vladimira Hinic and Tim Roloff and Adrian Egli and Muhammad Ali Syed and Oliver Nolte},
journal = {JAC-antimicrobial resistance},
year = {2026},
month = oct,
doi = {10.1093/jacamr/dlag233},
url = {https://europepmc.org/article/MED/42921071},
note = {CC BY},
}
RIS
TY - JOUR
TI - Molecular characterization of carbapenemase-producing Enterobacterales from Peshawar City, Khyber Pakhtunkhwa, Pakistan.
AU - Stefano Mancini
AU - Irfan Ullah
AU - Helena M B Seth-Smith
AU - Natalia Kolesnik-Goldmann
AU - Vladimira Hinic
AU - Tim Roloff
AU - Adrian Egli
AU - Muhammad Ali Syed
AU - Oliver Nolte
PY - 2026
DA - 2026/10/23
JO - JAC-antimicrobial resistance
DO - 10.1093/jacamr/dlag233
UR - https://europepmc.org/article/MED/42921071
AB - Background/objectives The dissemination of multidrug-resistant Enterobacterales poses a critical public health challenge, particularly in resource-limited regions with high antimicrobial use and limited surveillance. We analysed the phenotypic and genotypic resistance profiles of carbapenemase-producing Enterobacterales collected in 2023 from three tertiary care hospitals in Peshawar, Pakistan.Methods We performed antimicrobial susceptibility testing on 32 Enterobacterales isolates suspected of carbapenemase production using disk diffusion, gradient diffusion, and broth microdilution according to EUCAST guidelines. We conducted whole-genome sequencing to identify resistance genes, sequence types, and mutations associated with reduced susceptibility to novel β-lactams.Results The collection comprised 16 Escherichia coli, 13 Klebsiella pneumoniae, and 3 Proteus mirabilis isolates. The predominant carbapenemase gene was bla NDM-5 (90.6%), frequently combined with bla OXA-48-like variants (46.9%). ESBL genes, mainly bla CTX-M-15, were common (78.1%), while CMY-type AmpC β-lactamases were detected in 28.1% of isolates. Insertions in the PBP3-encoding gene ftsI and CMY co-production were associated with elevated aztreonam-avibactam MICs in E.coli. Reduced cefiderocol susceptibility was observed mainly among NDM-producing E. coli ST2 isolates carrying cirA disruption and ftsI insertions. All isolates remained susceptible to colistin, most of them to gentamicin (84.4%), and exhibited wild-type MIC-distributions for tigecycline, and eravacycline. Genomic analysis identified clustering of high-risk clones, suggesting ongoing local transmission. Notably, 11/13 K. pneumoniae ST147 isolates carried multiple virulence-associated genes consistent with hypervirulence.Conclusions High-risk NDM-producing Enterobacterales with increasingly complex resistance and virulence mechanisms are circulating in Pakistan, including determinants compromising last-line β-lactams. Strengthened genomic surveillance is essential to guide therapy and limit further spread.
SN - 2632-1823
ER -