ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2020
Emergence of Polymyxin Resistance in Clinical Klebsiella pneumoniae Through Diverse Genetic Adaptations: A Genomic, Retrospective Cohort Study.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 75 citations in OpenAlex.
- Review
- A posttranslational modification of fimbriae drives pathogenicity inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular analysis of polymyxin B resistance in clinical carbapenem-resistant Klebsiella pneumoniae isolates from a large tertiary care teaching hospital in Southwest China.BMC microbiology · 2026Article
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- Eravacycline monotherapy and combination therapy against KPC-2- and NDM-1-co- producingFrontiers in microbiology · 2026Article
- Inferring asymptomatic carriers of antimicrobial-resistant organisms in hospitals using genomic, microbiological and patient mobility data.Nature communications · 2025Article
- Status of Antibiotic Susceptibility of Polymyxin B And Colistin in the Treatment of Carbapenem Resistant Gram Negative Bacterial Infections: An Observational Study.JNMA; journal of the Nepal Medical Association · 2025Observational
- Regional Genomic and Phylogenomic Insights into Multidrug and Colistin-Resistant Klebsiella pneumoniae Strains from Tanzania, Kenya, Uganda, and Ethiopia.Current microbiology · 2025Article
- A novel post-translational modification of fimbriae drives pathogenicity inbioRxiv : the preprint server for biology · 2025Article
- Coexistence of carbapenem resistance and hypervirulence in clinical Klebsiella pneumoniae isolates: a molecular and phenotypic analysis.BMC infectious diseases · 2025Article
- Prevalence of polymyxin heteroresistance in Klebsiella pneumoniae under sustained antibiotic selection during experimental evolution.Archives of microbiology · 2025Article
- Metabolic Rewiring of Bacterial Pathogens in Response to Antibiotic Pressure-A Molecular Perspective.International journal of molecular sciences · 2025Review
- BIOMARKER DETECTION FOR DISEASE CLASSIFICATION IN LONGITUDINAL MICROBIOME DATA.The annals of applied statistics · 2025Article
- Risk Factors and Prognosis of Polymyxin- and Carbapenem-Resistant Enterobacteriaceae Infections: A Propensity-Matched Real-World Study.Microorganisms · 2025Article
- Multidrug-resistant hypervirulentFuture microbiology · 2025Review
- CombatingFrontiers in cellular and infection microbiology · 2025Review
- Mechanisms of Antimicrobial Resistance inInfection and drug resistance · 2025Review
- Article
- A nosocomial outbreak of colistin and carbapenem-resistant hypervirulent Klebsiella pneumoniae in a large teaching hospital.Scientific reports · 2024Article
- Retrospective analysis of molecular characteristics, risk factors, and outcomes in carbapenem-resistant Klebsiella pneumoniae bloodstream infections.BMC microbiology · 2024Observational
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundPolymyxins are antimicrobials of last resort for the treatment of carbapenem-resistant Enterobacteriaceae, but resistance in 5% to >40% isolates has been reported. We conducted a genomic survey of clinical polymyxin-resistant (PR) Klebsiella pneumoniae to determine the molecular mechanisms of PR and the role of polymyxin exposure versus transmission in PR emergence.
methodsWe included 88 patients with PR K. pneumoniae from 2011-2018 and collected demographic, antimicrobial exposure, and infection data. Whole-genome sequencing was performed on 388 isolates, including 164 PR isolates. Variant calling and insertion sequence detection were performed, focusing on key genes associated with PR (mgrB, crrAB, phoPQ, and pmrAB). We conducted phylogenetic analyses of key K. pneumoniae multi-locus sequence types (ST258, ST17, ST307, and ST392).
resultsPolymyxin exposure was documented in 53/88 (60%) patients prior to PR detection. Through an analysis of key PR genes, we detected 129 individual variants and 72 unique variant combinations in PR isolates. This included multiple, distinct changes in 36% of patients with serial PR isolates. Insertion sequence disruption was limited to mgrB (P < .001). Polymyxin minimum inhibitory concentrations showed stepwise increases with the number of PR genes affected (P < .001). When clusters containing PR isolates in ≥2 patients were analyzed, 10/14 had multiple genetic events leading to PR.
conclusionsMolecular mechanisms leading to PR in clinical K. pneumoniae isolates are remarkably heterogenous, even within clusters or individual patients. Polymyxin exposure with de novo PR emergence led to PR in the majority of patients, rather than transmission. Optimizing polymyxin use should be a key strategy in stopping the spread of PR.
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