TY - JOUR
T1 - Predicting β-lactam resistance using whole genome sequencing in Klebsiella pneumoniae
T2 - the challenge of β-lactamase inhibitors
AU - Hujer, Andrea M.
AU - Long, S. Wesley
AU - Olsen, Randall J.
AU - Taracila, Magdalena A.
AU - Rojas, Laura J.
AU - Musser, James M.
AU - Bonomo, Robert A.
N1 - Copyright © 2020 Elsevier Inc. All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - Avibactam
KW - Aztreonam
KW - Ceftolozane
KW - Klebsiella pneumoniae
KW - beta-Lactamase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85089725456&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089725456&partnerID=8YFLogxK
U2 - 10.1016/j.diagmicrobio.2020.115149
DO - 10.1016/j.diagmicrobio.2020.115149
M3 - Article
C2 - 32858260
AN - SCOPUS:85089725456
SN - 0732-8893
VL - 98
JO - Diagnostic Microbiology and Infectious Disease
JF - Diagnostic Microbiology and Infectious Disease
IS - 3
M1 - 115149
ER -