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Experimental Therapeutics

Exploring Aztreonam in Combination with Ceftazidime-Avibactam or Meropenem-Vaborbactam as Potential Treatments for Metallo- and Serine-β-Lactamase-Producing Enterobacteriaceae

M. Biagi, T. Wu, M. Lee, S. Patel, D. Butler, E. Wenzler
M. Biagi
aCollege of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA
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T. Wu
aCollege of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA
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M. Lee
aCollege of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA
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S. Patel
aCollege of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA
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D. Butler
aCollege of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA
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E. Wenzler
aCollege of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA
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  • ORCID record for E. Wenzler
DOI: 10.1128/AAC.01426-19
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    FIG 1

    Mean log10 CFU/ml versus time profiles for each drug at the highest concentration tested against the four E. coli strains. Aztreonam is shown at fCmax (A and C) and at 4× MIC (B and D). Ceftazidime and meropenem are shown at fCmax in all panels. Curves represent average concentrations from triplicate experiments.

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    FIG 2

    Mean log10 CFU/ml versus time profiles for each drug at the highest concentration tested against the four K. pneumoniae strains. (A to D) All drugs are shown at fCmax. Curves represent average concentrations from triplicate experiments.

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    FIG 3

    Mean log10 CFU/ml versus time profiles for each individual drug at the highest concentration tested that demonstrated no activity and triple-drug combinations against the four E. coli strains. (A to D) Ceftazidime-avibactam and meropenem-vaborbactam are shown at fCmax alone and in combination. (A and C) Aztreonam is shown at fCmax alone and in combination. Aztreonam is shown at 1× MIC (B) and at 0.25× MIC (D) alone and in combination. Curves represent average concentrations from triplicate experiments.

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    FIG 4

    Mean log10 CFU/ml versus time profiles for each individual drug at the highest concentration tested that demonstrated no activity and triple drug combinations against the four K. pneumoniae strains. (A to D) All drugs are shown alone and in combination at fCmax. Curves represent average concentrations from triplicate experiments.

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  • TABLE 1

    Genotypic and phenotypic susceptibility of tested serine and NDM-producing E. coli and K. pneumoniae isolatesa

    TABLE 1
    • ↵a Avibactam and vaborbactam were tested at fixed concentrations of 4 and 8 mg/liter, respectively.

    • ↵b ATM, aztreonam; AVI, avibactam; VBR, vaborbactam; CAZ, ceftazidime; MER, meropenem.

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      Figure S1, Figure S2, Table S1, Table S2, Table S3, Table S4

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Exploring Aztreonam in Combination with Ceftazidime-Avibactam or Meropenem-Vaborbactam as Potential Treatments for Metallo- and Serine-β-Lactamase-Producing Enterobacteriaceae
M. Biagi, T. Wu, M. Lee, S. Patel, D. Butler, E. Wenzler
Antimicrobial Agents and Chemotherapy Nov 2019, 63 (12) e01426-19; DOI: 10.1128/AAC.01426-19

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Exploring Aztreonam in Combination with Ceftazidime-Avibactam or Meropenem-Vaborbactam as Potential Treatments for Metallo- and Serine-β-Lactamase-Producing Enterobacteriaceae
M. Biagi, T. Wu, M. Lee, S. Patel, D. Butler, E. Wenzler
Antimicrobial Agents and Chemotherapy Nov 2019, 63 (12) e01426-19; DOI: 10.1128/AAC.01426-19
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    • ABSTRACT
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KEYWORDS

metallo-β-lactamase
NDM
aztreonam
ceftazidime-avibactam
meropenem-vaborbactam
synergy

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