ArticleAntimicrobial agents and chemotherapy2015
Rapid induction of high-level carbapenem resistance in heteroresistant KPC-producing Klebsiella pneumoniae.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Recurrent infections caused by ESBL-producing enterobacterales with or without subsequent development of distinct carbapenem-resistant phenotypes: differential driving factors and impact on outcome.JAC-antimicrobial resistance · 2026Article
- ESBL-ProducingMicroorganisms · 2025Article
- Emergence of population heterogeneity in Klebsiella pneumoniae with a blaJournal of biomedical science · 2025Article
- Reporting antimicrobial susceptibility and detection of carbapenemase production in single and double carbapenemase-producing Gram-negative clinical isolates: a nationwide proficiency study.Frontiers in microbiology · 2025Article
- Proteome analysis, genetic characterization, and antibiotic resistance patterns of Klebsiella pneumoniae clinical isolates.AMB Express · 2024Article
- LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases.Biomolecules · 2024Review
- Outer-Membrane Permeabilization, LPS Transport Inhibition: Activity, Interactions, and Structures of Thanatin Derived Antimicrobial Peptides.International journal of molecular sciences · 2024Article
- Structures, Interactions and Activity of the N-Terminal Truncated Variants of Antimicrobial Peptide Thanatin.Antibiotics (Basel, Switzerland) · 2024Article
- Detection and characterization of eravacycline heteroresistance in clinical bacterial isolates.Frontiers in microbiology · 2024Article
- Ceftazidime-Avibactam Treatment forAntibiotics (Basel, Switzerland) · 2023Article
- Whole-Genome Sequence Analysis of Carbapenem-Heteroresistant Klebsiella pneumoniae and Escherichia coli Isolates.Current microbiology · 2022Article
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- Direct Identification, Antimicrobial Susceptibility Testing, and Extended-Spectrum β-Lactamase and Carbapenemase Detection in Gram-Negative Bacteria Isolated from Blood Cultures.Infection and drug resistance · 2022Article
- Antibiotic Heteroresistance inInternational journal of molecular sciences · 2021Review
- Zidovudine enhances activity of carbapenems against NDM-1-producing Enterobacteriaceae.The Journal of antimicrobial chemotherapy · 2021Article
- A Dual Enzyme-Based Biochemical Test Rapidly Detects Third-Generation Cephalosporin-Resistant CTX-M-Producing Uropathogens in Clinical Urine Samples.Microbial drug resistance (Larchmont, N.Y.) · 2021Article
- Risk factors and outcome associated with infection or colonization due to carbapenem-heteroresistantJAC-antimicrobial resistance · 2021Article
- A rapid, antibiotic susceptibility test for multidrug-resistant, Gram-negative bacterial uropathogens using the biochemical assay, DETECT.Journal of microbiological methods · 2021Article
- ISmBio · 2021Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Enterobacteriaceae strains producing the Klebsiella pneumoniae carbapenemase (KPC) have disseminated worldwide, causing an urgent threat to public health. KPC-producing strains often exhibit low-level carbapenem resistance, which may be missed by automated clinical detection systems. In this study, eight Klebsiella pneumoniae strains with heterogeneous resistance to imipenem were used to elucidate the factors leading from imipenem susceptibility to high-level resistance as defined by clinical laboratory testing standards. Time-kill analysis with an inoculum as low as 3 × 10(6) CFU/ml and concentrations of imipenem 8- and 16-fold higher than the MIC resulted in the initial killing of 99.9% of the population. However, full recovery of the population occurred by 20 h of incubation in the same drug concentrations. Population profiles showed that recovery was mediated by a heteroresistant subpopulation at a frequency of 2 × 10(-7) to 3 × 10(-6). Samples selected 2 h after exposure to imipenem were as susceptible as the unexposed parental strain and produced the major outer membrane porin OmpK36. However, between 4 to 8 h after exposure, OmpK36 became absent, and the imipenem MIC increased at least 32-fold. Individual colonies isolated from cultures after 20 h of exposure revealed both susceptible and resistant subpopulations. Once induced, however, the high-level imipenem resistance was maintained, and OmpK36 remained unexpressed even without continued carbapenem exposure. This study demonstrates the essential coordination between blaKPC and ompK36 expression mediating high-level imipenem resistance from a population of bacteria that initially exhibits a carbapenem-susceptibility phenotype.
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