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Peer-reviewedCC BY 4.0Frontiers in Microbiology

Clinical and public genomic comparisons of carbapenem resistance in Pseudomonas aeruginosa

Abstract

BackgroundCross-setting comparisons of carbapenem resistance may reflect clinical contexts and selective genomic sampling. We examined reproducibility on two independent scales.MethodsWe analysed retrospective adult cohorts from a Chinese hospital (n = 1,362) and the Medical Information Mart for Intensive Care IV (MIMIC-IV) v3.1 (n = 3,251), along with 26,417 publicly submitted clinical Pseudomonas aeruginosa BioSamples. Our clinical analyses compared susceptibility-defined carbapenem-resistant Pseudomonas aeruginosa (CRPA), evaluated outcomes, adjusting for associations, and conducted exploratory reciprocal model transport. Our genomic analyses examined annotated determinants, submission-year patterns, single-nucleotide polymorphism (SNP) clusters, and co-resistance, including cluster-weighted sensitivity analyses.ResultsCRPA proportions were 36.9 and 9.3% in the two institutions. Unadjusted in-hospital mortality and post-index hospital stay were higher among patients with CRPA. Adjusted association directions agreed for 13 of 18 covariates. Transported models showed modest discrimination (area under the curves [AUCs], 0.641 and 0.619) and marked miscalibration (calibration slopes, 0.45 and 0.52). Among the included public Biosamples, 60.7% carried a defined carbapenem-associated determinant and 24.4% carried an acquired carbapenemase. Chinese submissions had higher serine-carbapenemase positivity, whereas US submissions had higher metallo-β-lactamase and chromosomal-determinant positivity. The country OR for blaKPC changed from 8.04 in the full sample to 1.59 in the cluster-assigned weighted analysis; the OR for acquired carbapenemase changed from 1.32 to 0.67.ConclusionClinical associations may recur without supporting a reliable transported prediction. Genomic contrasts are sensitive to sampling and analysis population. These exploratory, unlinked findings neither establish causal effects nor estimate national prevalence; genomic results do not confirm phenotypic CRPA.

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BibTeX
@article{li2026clinical,
  title = {{Clinical and public genomic comparisons of carbapenem resistance in Pseudomonas aeruginosa}},
  author = {Cheng-En Li and Ying-Ying Shen and Ru-Qin Yi and Wei Chen and Ding Zhang and Sheng-Hui Miao and Zhi-Rong Zhang and Zhao-Kun Fan},
  journal = {Frontiers in Microbiology},
  year = {2026},
  month = nov,
  doi = {10.3389/fmicb.2026.2002985},
  url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.2002985},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Clinical and public genomic comparisons of carbapenem resistance in Pseudomonas aeruginosa
AU  - Cheng-En Li
AU  - Ying-Ying Shen
AU  - Ru-Qin Yi
AU  - Wei Chen
AU  - Ding Zhang
AU  - Sheng-Hui Miao
AU  - Zhi-Rong Zhang
AU  - Zhao-Kun Fan
PY  - 2026
DA  - 2026/11/05
JO  - Frontiers in Microbiology
DO  - 10.3389/fmicb.2026.2002985
UR  - https://www.frontiersin.org/articles/10.3389/fmicb.2026.2002985
AB  - BackgroundCross-setting comparisons of carbapenem resistance may reflect clinical contexts and selective genomic sampling. We examined reproducibility on two independent scales.MethodsWe analysed retrospective adult cohorts from a Chinese hospital (n = 1,362) and the Medical Information Mart for Intensive Care IV (MIMIC-IV) v3.1 (n = 3,251), along with 26,417 publicly submitted clinical Pseudomonas aeruginosa BioSamples. Our clinical analyses compared susceptibility-defined carbapenem-resistant Pseudomonas aeruginosa (CRPA), evaluated outcomes, adjusting for associations, and conducted exploratory reciprocal model transport. Our genomic analyses examined annotated determinants, submission-year patterns, single-nucleotide polymorphism (SNP) clusters, and co-resistance, including cluster-weighted sensitivity analyses.ResultsCRPA proportions were 36.9 and 9.3% in the two institutions. Unadjusted in-hospital mortality and post-index hospital stay were higher among patients with CRPA. Adjusted association directions agreed for 13 of 18 covariates. Transported models showed modest discrimination (area under the curves [AUCs], 0.641 and 0.619) and marked miscalibration (calibration slopes, 0.45 and 0.52). Among the included public Biosamples, 60.7% carried a defined carbapenem-associated determinant and 24.4% carried an acquired carbapenemase. Chinese submissions had higher serine-carbapenemase positivity, whereas US submissions had higher metallo-β-lactamase and chromosomal-determinant positivity. The country OR for blaKPC changed from 8.04 in the full sample to 1.59 in the cluster-assigned weighted analysis; the OR for acquired carbapenemase changed from 1.32 to 0.67.ConclusionClinical associations may recur without supporting a reliable transported prediction. Genomic contrasts are sensitive to sampling and analysis population. These exploratory, unlinked findings neither establish causal effects nor estimate national prevalence; genomic results do not confirm phenotypic CRPA.
SN  - 1664-302X
ER  -