Assessing the in vitro Impact of Ceftazidime on Aztreonam/avibactam Susceptibility Testing for Highly Resistant MBL-producing Enterobacterales

Details

• Alternative Title:
  J Antimicrob Chemother
• Personal Author:
  BHATNAGAR, Amelia ; RANSOM, Eric M. ; MACHADO, María-José ; BOYD, Sandra ; REESE, Natashia ; ANDERSON, Karen ; LONSWAY, David ; ELKINS, Christopher A. ; RASHEED, J. Kamile ; PATEL, Jean B. ; KARLSSON, Maria ; BROWN, Allison C. ; LUTGRING, Joseph D.
• 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.
  
  
• Keywords:
  Anti-Bacterial Agents Azabicyclo Compounds Aztreonam Beta-Lactamases Ceftazidime Drug Combinations Microbial Sensitivity Tests
• Source:
  J Antimicrob Chemother. 76(4):979-983
• Pubmed ID:
  33367916
• Pubmed Central ID:
  PMC10838604
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/
• Volume:
  76
• Issue:
  4
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:f975e16ff13ae190aff32c442f1af14bac77569bae2825e41bbf2485f17b42a1
• Download URL:
  https://stacks.cdc.gov/view/cdc/147677/cdc_147677_DS1.pdf
• File Type:
  [PDF - 469.39 KB ]