Heteroresistance to piperacillin/tazobactam in Klebsiella pneumoniae is mediated by increased copy number of multiple β-lactamase genes.
| Autor: | Babiker A; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Lohsen S; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Van Riel J; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Hjort K; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden., Weiss DS; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Andersson DI; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden., Satola S; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. |
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| Jazyk: | angličtina |
| Zdroj: | JAC-antimicrobial resistance [JAC Antimicrob Resist] 2024 Apr 10; Vol. 6 (2), pp. dlae057. Date of Electronic Publication: 2024 Apr 10 (Print Publication: 2024). |
| DOI: | 10.1093/jacamr/dlae057 |
| Abstrakt: | Background: Piperacillin/tazobactam is a β-lactam/β-lactamase inhibitor combination with a broad spectrum of activity that is often used as empirical and/or targeted therapy among hospitalized patients. Heteroresistance (HR) is a form of antibiotic resistance in which a minority population of resistant cells coexists with a majority susceptible population that has been found to be a cause of antibiotic treatment failure in murine models. Objectives: To determine the prevalence of HR and mechanisms of HR to piperacillin/tazobactam among Klebsiella pneumoniae bloodstream infection (BSI) isolates. Materials: From July 2018 to June 2021, K. pneumoniae piperacillin/tazobactam-susceptible BSI isolates were collected from two tertiary hospitals in Atlanta, GA, USA. Only first isolates from each patient per calendar year were included. Population analysis profiling (PAP) and WGS were performed to identify HR and its mechanisms. Results: Among 423 K. pneumoniae BSI isolates collected during the study period, 6% (25/423) were found to be HR with a subpopulation surviving above the breakpoint. WGS of HR isolates grown in the presence of piperacillin/tazobactam at concentrations 8-fold that of the MIC revealed copy number changes of plasmid-located β-lactamase genes bla Conclusions: Prevalence of HR to piperacillin/tazobactam among bloodstream isolates was substantial. The HR phenotype appears to be caused by tandem amplification of β-lactamase genes found on plasmids or plasmid copy number increase. This raises the possibility of dissemination of HR through horizontal gene transfer and requires further study. (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.) |
| Databáze: | MEDLINE |
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