ArticleInfection2025
High prevalence of polymyxin-heteroresistant carbapenem-resistant Klebsiella pneumoniae and its within-host evolution to resistance among critically ill scenarios.
Article in Infection, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic review and meta-analysis of colistin heteroresistance in Klebsiella pneumoniae isolates.BMC infectious diseases · 2025Pooled it
- Colistin Resistance in Critically Ill Adults: A Systematic Review of Epidemiological, Clinical, Laboratory, and Molecular Evidence.Microorganisms · 2026Review
- Beyond β-Lactams: Defining the Role of Eravacycline in Multidrug-Resistant and Metallo-β-Lactamase-Producing Infections.Antibiotics (Basel, Switzerland) · 2026Review
- In vitro and in vivo activity of colistin-nitroxoline combination against polymyxin heteroresistant carbapenem-resistant Klebsiella pneumoniae.BMC microbiology · 2026Article
- RNA Sequencing of Sepsis Patients Informs Tests to Quickly Diagnose Pathogens and Resistance.Shock (Augusta, Ga.) · 2026Article
- Polymyxin heteroresistance inJournal of medical microbiology · 2026Article
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Authors and funding
11 authors.
Funding
Abstract
purposeWe aimed to explore the prevalence and within-host evolution of resistance in polymyxin-heteroresistant carbapenem-resistant Klebsiella pneumoniae (PHR-CRKP) in critically ill patients.
methodsWe performed an epidemiological analysis of consecutive patients with PHR-CRKP from clinical cases. Our study investigated the within-host resistance evolution and its clinical significance during polymyxin exposure. Furthermore, we explored the mechanisms underlying the dynamic evolution of polymyxin resistance at both subpopulation and genetic levels, involved population analysis profile test, time-killing assays, competition experiments, and sanger sequencing. Additionally, comparative genomic analysis was performed on 713 carbapenemase-producing K. pneumoniae strains.
resultsWe enrolled 109 consecutive patients, and PHR-CRKP was found in 69.7% of patients without previous polymyxin exposure. 38.1% of PHR-CRKP isolates exhibited polymyxin resistance and led to therapeutic failure in critically ill scenarios. An increased frequency of resistant subpopulations was detected during PHR-CRKP evolution, with rapid regrowth of resistant subpopulations under high polymyxin concentrations, and a fitness cost in an antibiotic-free environment. Mechanistic analysis revealed that diverse mgrB insertions and pmrB hypermutations contributed to the dynamic changes in polymyxin susceptibility in dominant resistant subpopulations during PHR evolution, which were validated by comparative genomic analysis. Several deleterious mutations (e.g. pmrB
conclusionsOur study emphasizes the high prevalence of pre-existing heteroresistance in CRKP, which can lead to polymyxin resistance and fatal outcomes. Hence, it is essential to continuously monitor and observe the treatment response to polymyxins in appropriate critically ill scenarios.
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