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Emergence of ceftazidime/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate

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Emergence of ceftazidime/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate. / Both, Anna; Büttner, Henning; Huang, Jiabin; Perbandt, Markus; Belmar Campos, Cristina; Christner, Martin; Maurer, Florian P; Kluge, Stefan; König, Christina; Aepfelbacher, Martin; Wichmann, Dominic; Rohde, Holger.

in: J ANTIMICROB CHEMOTH, Jahrgang 72, Nr. 9, 01.09.2017, S. 2483-2488.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Both, A, Büttner, H, Huang, J, Perbandt, M, Belmar Campos, C, Christner, M, Maurer, FP, Kluge, S, König, C, Aepfelbacher, M, Wichmann, D & Rohde, H 2017, 'Emergence of ceftazidime/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate', J ANTIMICROB CHEMOTH, Jg. 72, Nr. 9, S. 2483-2488. https://doi.org/10.1093/jac/dkx179

APA

Both, A., Büttner, H., Huang, J., Perbandt, M., Belmar Campos, C., Christner, M., Maurer, F. P., Kluge, S., König, C., Aepfelbacher, M., Wichmann, D., & Rohde, H. (2017). Emergence of ceftazidime/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate. J ANTIMICROB CHEMOTH, 72(9), 2483-2488. https://doi.org/10.1093/jac/dkx179

Vancouver

Both A, Büttner H, Huang J, Perbandt M, Belmar Campos C, Christner M et al. Emergence of ceftazidime/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate. J ANTIMICROB CHEMOTH. 2017 Sep 1;72(9):2483-2488. https://doi.org/10.1093/jac/dkx179

Bibtex

@article{bcd9fc94dd6c4754bd285780a86d8e20,
title = "Emergence of ceftazidime/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate",
abstract = "Background: Avibactam is a novel broad-range β-lactamase inhibitor active against Ambler class A (including ESBL and KPC) and some Ambler class C and D (e.g. OXA-48) enzymes. We here report on the emergence of ceftazidime/avibactam resistance in clinical, multiresistant, OXA-48 and CTX-M-14-producing Klebsiella pneumoniae isolate DT12 during ceftazidime/avibactam treatment.Methods and results: Comparative whole-genome sequence analysis identified two SNPs in the CTX-M-14-encoding gene leading to two amino acid changes (P170S and T264I). Compared with WT CTX-M-14, expression of the CTX-M-14 Δ170Δ264 isoform in Escherichia coli led to a >64- and 16-fold increase in ceftazidime and ceftazidime/avibactam MICs, respectively, functionally linking the observed SNPs and elevated MICs. The mutated CTX-M-14 isoform exhibited augmented ceftazidime hydrolytic activity, which was a reasonable cause for impaired susceptibility to avibactam inhibition. The P170S exchange in CTX-M-14 was found in association with elevated ceftazidime/avibactam MICs for independent K. pneumoniae isolates, but was not sufficient for full resistance. Apparently, additional CTX-M-independent mechanisms contribute to ceftazidime/avibactam resistance in K. pneumoniae DT12.Conclusions: This study on the molecular basis of ceftazidime/avibactam resistance in clinical K. pneumoniae emerging in vivo underscores the need for continuous monitoring of ceftazidime/avibactam susceptibility during therapy. Despite sustained inhibition of OXA-48, rapid development of CTX-M-14 isoforms exhibiting augmented ceftazidime hydrolytic activity may limit the usefulness of ceftazidime/avibactam monotherapies in infections caused by isolates carrying bla CTX-M-14 and bla OXA-48 .",
keywords = "Journal Article",
author = "Anna Both and Henning B{\"u}ttner and Jiabin Huang and Markus Perbandt and {Belmar Campos}, Cristina and Martin Christner and Maurer, {Florian P} and Stefan Kluge and Christina K{\"o}nig and Martin Aepfelbacher and Dominic Wichmann and Holger Rohde",
year = "2017",
month = sep,
day = "1",
doi = "10.1093/jac/dkx179",
language = "English",
volume = "72",
pages = "2483--2488",
journal = "J ANTIMICROB CHEMOTH",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "9",

}

RIS

TY - JOUR

T1 - Emergence of ceftazidime/avibactam non-susceptibility in an MDR Klebsiella pneumoniae isolate

AU - Both, Anna

AU - Büttner, Henning

AU - Huang, Jiabin

AU - Perbandt, Markus

AU - Belmar Campos, Cristina

AU - Christner, Martin

AU - Maurer, Florian P

AU - Kluge, Stefan

AU - König, Christina

AU - Aepfelbacher, Martin

AU - Wichmann, Dominic

AU - Rohde, Holger

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Background: Avibactam is a novel broad-range β-lactamase inhibitor active against Ambler class A (including ESBL and KPC) and some Ambler class C and D (e.g. OXA-48) enzymes. We here report on the emergence of ceftazidime/avibactam resistance in clinical, multiresistant, OXA-48 and CTX-M-14-producing Klebsiella pneumoniae isolate DT12 during ceftazidime/avibactam treatment.Methods and results: Comparative whole-genome sequence analysis identified two SNPs in the CTX-M-14-encoding gene leading to two amino acid changes (P170S and T264I). Compared with WT CTX-M-14, expression of the CTX-M-14 Δ170Δ264 isoform in Escherichia coli led to a >64- and 16-fold increase in ceftazidime and ceftazidime/avibactam MICs, respectively, functionally linking the observed SNPs and elevated MICs. The mutated CTX-M-14 isoform exhibited augmented ceftazidime hydrolytic activity, which was a reasonable cause for impaired susceptibility to avibactam inhibition. The P170S exchange in CTX-M-14 was found in association with elevated ceftazidime/avibactam MICs for independent K. pneumoniae isolates, but was not sufficient for full resistance. Apparently, additional CTX-M-independent mechanisms contribute to ceftazidime/avibactam resistance in K. pneumoniae DT12.Conclusions: This study on the molecular basis of ceftazidime/avibactam resistance in clinical K. pneumoniae emerging in vivo underscores the need for continuous monitoring of ceftazidime/avibactam susceptibility during therapy. Despite sustained inhibition of OXA-48, rapid development of CTX-M-14 isoforms exhibiting augmented ceftazidime hydrolytic activity may limit the usefulness of ceftazidime/avibactam monotherapies in infections caused by isolates carrying bla CTX-M-14 and bla OXA-48 .

AB - Background: Avibactam is a novel broad-range β-lactamase inhibitor active against Ambler class A (including ESBL and KPC) and some Ambler class C and D (e.g. OXA-48) enzymes. We here report on the emergence of ceftazidime/avibactam resistance in clinical, multiresistant, OXA-48 and CTX-M-14-producing Klebsiella pneumoniae isolate DT12 during ceftazidime/avibactam treatment.Methods and results: Comparative whole-genome sequence analysis identified two SNPs in the CTX-M-14-encoding gene leading to two amino acid changes (P170S and T264I). Compared with WT CTX-M-14, expression of the CTX-M-14 Δ170Δ264 isoform in Escherichia coli led to a >64- and 16-fold increase in ceftazidime and ceftazidime/avibactam MICs, respectively, functionally linking the observed SNPs and elevated MICs. The mutated CTX-M-14 isoform exhibited augmented ceftazidime hydrolytic activity, which was a reasonable cause for impaired susceptibility to avibactam inhibition. The P170S exchange in CTX-M-14 was found in association with elevated ceftazidime/avibactam MICs for independent K. pneumoniae isolates, but was not sufficient for full resistance. Apparently, additional CTX-M-independent mechanisms contribute to ceftazidime/avibactam resistance in K. pneumoniae DT12.Conclusions: This study on the molecular basis of ceftazidime/avibactam resistance in clinical K. pneumoniae emerging in vivo underscores the need for continuous monitoring of ceftazidime/avibactam susceptibility during therapy. Despite sustained inhibition of OXA-48, rapid development of CTX-M-14 isoforms exhibiting augmented ceftazidime hydrolytic activity may limit the usefulness of ceftazidime/avibactam monotherapies in infections caused by isolates carrying bla CTX-M-14 and bla OXA-48 .

KW - Journal Article

U2 - 10.1093/jac/dkx179

DO - 10.1093/jac/dkx179

M3 - SCORING: Journal article

C2 - 28637339

VL - 72

SP - 2483

EP - 2488

JO - J ANTIMICROB CHEMOTH

JF - J ANTIMICROB CHEMOTH

SN - 0305-7453

IS - 9

ER -