Predicting β-lactam resistance using whole genome sequencing in Klebsiella pneumoniae: the challenge of β-lactamase inhibitors
Although multiple antimicrobial resistance (AMR) determinants can confer the same in vitro antimicrobial susceptibility testing (AST) phenotype, their differing effect on optimal therapeutic choices is uncertain. Using a large population-based collection of clinical strains spanning a 3.5-year perio...
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| Veröffentlicht in: | Diagnostic microbiology and infectious disease 2020-11, Vol.98 (3), p.115149-115149, Article 115149 |
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| container_title | Diagnostic microbiology and infectious disease |
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| creator | Hujer, Andrea M. Long, S. Wesley Olsen, Randall J. Taracila, Magdalena A. Rojas, Laura J. Musser, James M. Bonomo, Robert A. |
| description | Although multiple antimicrobial resistance (AMR) determinants can confer the same in vitro antimicrobial susceptibility testing (AST) phenotype, their differing effect on optimal therapeutic choices is uncertain. Using a large population-based collection of clinical strains spanning a 3.5-year period, we applied WGS to detect inhibitor resistant (IR), extended-spectrum β-lactamase (ESBL), and carbapenem resistant (CR) β-lactamase (bla) genes and compared the genotype to the AST phenotype in select isolates. All blaNDM-1 (9/9) and the majority of blaNDM-1/OXA-48 (3/4) containing isolates were resistant to CAZ/AVI as predicted by WGS. The combination of ATM and CAZ/AVI restored susceptibility by disk diffusion assay. Unexpectedly, clinical Kp isolates bearing blaKPC-8 (V240G) and blaKPC-14 (G242 and T243 deletion) did not test fully resistant to CAZ/AVI. Lastly, despite the complexity of the β-lactamase background, CAZ/AVI retained potency. Presumed phenotypes conferred by AMR determinants need to be tested if therapeutic decisions are being guided by their presence or absence. |
| doi_str_mv | 10.1016/j.diagmicrobio.2020.115149 |
| format | Article |
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Wesley ; Olsen, Randall J. ; Taracila, Magdalena A. ; Rojas, Laura J. ; Musser, James M. ; Bonomo, Robert A.</creator><creatorcontrib>Hujer, Andrea M. ; Long, S. Wesley ; Olsen, Randall J. ; Taracila, Magdalena A. ; Rojas, Laura J. ; Musser, James M. ; Bonomo, Robert A.</creatorcontrib><description>Although multiple antimicrobial resistance (AMR) determinants can confer the same in vitro antimicrobial susceptibility testing (AST) phenotype, their differing effect on optimal therapeutic choices is uncertain. Using a large population-based collection of clinical strains spanning a 3.5-year period, we applied WGS to detect inhibitor resistant (IR), extended-spectrum β-lactamase (ESBL), and carbapenem resistant (CR) β-lactamase (bla) genes and compared the genotype to the AST phenotype in select isolates. All blaNDM-1 (9/9) and the majority of blaNDM-1/OXA-48 (3/4) containing isolates were resistant to CAZ/AVI as predicted by WGS. The combination of ATM and CAZ/AVI restored susceptibility by disk diffusion assay. Unexpectedly, clinical Kp isolates bearing blaKPC-8 (V240G) and blaKPC-14 (G242 and T243 deletion) did not test fully resistant to CAZ/AVI. Lastly, despite the complexity of the β-lactamase background, CAZ/AVI retained potency. 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| ispartof | Diagnostic microbiology and infectious disease, 2020-11, Vol.98 (3), p.115149-115149, Article 115149 |
| issn | 0732-8893 1879-0070 |
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| source | ScienceDirect Journals (5 years ago - present) |
| subjects | Avibactam Aztreonam beta-Lactamase inhibitors Ceftolozane Klebsiella pneumoniae |
| title | Predicting β-lactam resistance using whole genome sequencing in Klebsiella pneumoniae: the challenge of β-lactamase inhibitors |
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