Expanded Antimicrobial Susceptibility Testing for Hard-to-Treat Infections (ExAST)
AR Lab Network – Antibiotic Resistance Laboratory Network
AST – antimicrobial susceptibility testing
CLIA – Clinical Laboratory Improvement Amendments
CRE- Carbapenem Resistant Enterobacterales
ExAST – Expanded Antimicrobial Susceptibility Testing for Hard-to-Treat Infections
FDA – U.S. Food and Drug Administration
IMP – Integron-encoded metallo-β-lactamase
IDSA- Infectious Diseases Society of America
NDM – New Delhi metallo-β-lactamase
mCIM – modified carbapenemase inactivation method
MIC – minimum inhibitory concentration
PCR – polymerase chain reaction
VIM – Verona integron-encoded metallo-β-lactamase
AST is a type of lab test that cultures (grows) germs such as bacteria to determine how sensitive the germ is to different antibiotics.
The test results can be used to help select the best antibiotic to treat an infection. This helps improve patient outcomes and helps slow the development of antibiotic resistance.
When antibiotics are recently approved for use, it can take years before susceptibility tests for these antibiotics are made available in clinical labs. To help address this challenge, CDC’s AR Lab Network provides testing to help guide clinical decision making for highly resistant MBL-producing Enterobacterales.
This AR Lab Network testing uses inkjet printing technology—a digital dispenser—to prepare custom broth microdilution panels with these new treatment options. The testing allows for a short turnaround time and is provided free of charge to improve patient care. The digital dispensing method provides CLIA-compliant drug susceptibility testing that is consistent among laboratories.
What isolates are tested through ExAST?
The AR Lab Network tests isolates of highly resistant Enterobacterales that carry MBLs. MBLs make bacteria resistant to a broad range of antibiotics, including carbapenems, which are often used to treat antibiotic-resistant infections.
What testing is performed?
Using the Hewlett-Packard D300e Digital Dispenser, highly resistant Enterobacterales isolates will be tested for susceptibility to the combination of aztreonam/avibactam. The combination drug aztreonam/avibactam is still in clinical development. However, because of limited treatment options, the IDSA’s Guidance on Treatment of Antimicrobial Resistant Gram-Negative Infectionsexternal icon recommends this combination as a treatment option for serious infections caused by MBL-producing CRE. Susceptibility results will be reported for ceftazidime/avibactam, aztreonam, and aztreonam/avibactam to help assess utility of combination therapy.
Isolates will also be tested for:
- Susceptibility to more than 20 other antibiotics using a commercially available comprehensive broth microdilution panel
- Carbapenemase production using the mCIM
- MBL and other carbapenemase genes
What isolates should be submitted?
Clinical or public health labs can request testing for Enterobacterales isolates that:
- Are not susceptible to all β-lactams tested, including either ceftazidime/avibactam or meropenem/vaborbactam (these may be MBL-producing isolates that cause infections with few effective treatment options)
- Possess at least one MBL gene (blaNDM, blaVIM, or blaIMP) confirmed by a molecular test
Requests must be accompanied by preliminary lab testing results, including AST results and/or molecular results, to confirm inclusion criteria have been met.
How do I request testing?
Healthcare, clinical, and public health labs—email your AR Lab Network regional lab to request testing and instructions for submitting isolates. Contact information can be found on the About AR Lab Network webpage.
How long does Expanded AST take to get results, and who is notified?
Susceptibility results for confirmed MBL-producing isolates will be returned within 3 business days to help guide treatment decisions. The AR Lab Network regional labs will notify the submitter and public health officials if MBL-producing isolates are confirmed to have an aztreonam/avibactam MIC ≥ 8/4 µg/mL.