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
ExAST – Expanded Antimicrobial Susceptibility Testing for Hard-to-Treat Infections
FDA – U.S. Food and Drug Administration
IMP – Integron-encoded metallo-β-lactamases
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 is piloting a program to help labs and clinicians decide if new-to-market antibiotics can effectively treat highly resistant infections caused by MBL-producing Enterobacteriaceae.
In 2019, the AR Lab Network adopted new technology—the Hewlett-Packard D300e Digital Dispenser—to perform expanded AST using inkjet printing technology to prepare MIC panels with these new treatment options, free of charge, and a short turnaround times to improve patient care. The digital dispensing method will provide CLIA-compliant reference broth microdilution testing that is consistent among laboratories.
What isolates are tested through ExAST?
The AR Lab Network tests isolates of highly resistant Enterobacteriaceae 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 Enterobacteriaceae isolates will be tested for susceptibility to the combination therapy aztreonam/avibactam. The combination therapy of aztreonam/avibactam is still in development. However, because of limited treatment options, the Sanford Guide recommends this combination for treatment of serious infections caused by MBL-producing gram-negative bacteria. 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 Enterobacteriaceae isolates that:
- Test non-susceptible to all beta-lactams, including either ceftazidime/avibactam or meropenem/vaborbactam (these isolates may be MBL-producing isolates with few effective treatment options)
- Possess MBL genes (NDM, VIM, or IMP) 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 should 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 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.