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Assessing the in vitro Impact of Ceftazidime on Aztreonam/avibactam Susceptibility Testing for Highly Resistant MBL-producing Enterobacterales
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3 12 2021
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Source: J Antimicrob Chemother. 76(4):979-983
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Alternative Title:J Antimicrob Chemother
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Description:Background
Aztreonam/avibactam is a combination agent that shows promise in treating infections caused by highly antibiotic-resistant MBL-producing Enterobacterales. This combination can be achieved by combining two FDA-approved drugs: ceftazidime/avibactam and aztreonam. It is unknown whether ceftazidime in the combination ceftazidime/aztreonam/avibactam has a synergistic or antagonistic effect on the in vitro activity of aztreonam/avibactam by significantly increasing or decreasing the MIC.
Objective
To determine whether increasing ceftazidime concentrations affect the MICs of aztreonam/avibactam alone.
Methods
A custom 8×8 chequerboard broth microdilution (BMD) panel was made using a digital dispenser (Hewlett-Packard, Corvallis, OR). The panel included orthogonal two-fold dilution series of aztreonam and ceftazidime ranging from 0.5 mg/L to 64 mg/L. Avibactam was kept constant at 4 mg/L throughout the chequerboard. Thirty-seven Enterobacterales isolates from the CDC & FDA AR Isolate Bank or CDC’s internal collection with intermediate or resistant interpretations to aztreonam and ceftazidime/avibactam were included for testing. All isolates harbored at least one of the following MBL genes: blaIMP, blaNDM, or blaVIM.
Results
Regardless of the concentration of ceftazidime, aztreonam/avibactam with ceftazidime MICs for all 37 isolates were within ±1 two-fold doubling dilution of the aztreonam/avibactam MIC.
Conclusions
Ceftazidime, in the combination ceftazidime/avibactam/aztreonam, did not affect the in vitro activity of aztreonam/avibactam in this sample of isolates. These findings can help assure clinical and public health laboratories that testing of aztreonam/avibactam by BMD can act as a reliable surrogate test when the combination of ceftazidime/avibactam and aztreonam is being considered for treatment of highly antibiotic-resistant MBL-producing Enterobacterales.
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Pubmed ID:33367916
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Pubmed Central ID:PMC10838604
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