Infections caused by isolates of carbapenemase-producing Enterobacteriaceae that are resistant to nearly all available antimicrobial agents are difficult to treat and a significant cause of morbidity and mortality. In contrast to serine carbapenemase (eg, KPC)- producers, isolates of Enterobacteriaceae that produce metallo-β-lactamases (MBL) are the most challenging, as these are resistant to meropenem-vaborbactam and ceftazidime-avibactam, the newest beta-lactam combination agents. However, isolates of Enterobacteriaceae with MBLs (eg, NDM, VIM, and IMP) have been shown to be susceptible to a combination of ceftazidime + avibactam + aztreonam. This combination is listed in the Sanford Guide as the primary option for treatment of serious infections caused by MBL-producing Enterobacteriaceae.1 Providing antimicrobial susceptibility testing of an isolate to aztreonam, ceftazidime-avibactam,2 and aztreonam-avibactam3 can provide useful information to guide patient treatment. Of note, the betalactam combination of aztreonam-avibactam is in Phase III clinical trials.
Most clinical laboratories find it difficult to test some of the newer antimicrobial agents that might warrant consideration for treatment of highly resistant organisms. It can take years before these drugs are available on commercial antimicrobial susceptibility testing systems used in clinical laboratories. The AR Lab Network4 has introduced a new testing approach to bridge the gap. A pilot program was initiated in 2019 at four of the seven AR Lab Network regional laboratories (Minnesota, New York Wadsworth, Tennessee, and Wisconsin) to provide expanded antimicrobial susceptibility testing (ExAST). This program will be extended in 2020 to the remaining AR Lab Network regional laboratories. However, ExAST is now available to all health care facilities in the United States and it is suggested that you contact your state or local public health laboratory (PHL) to determine which AR Lab Network regional laboratory is currently serving your facility for ExAST. Testing is available free-ofcharge for highly resistant isolates that meet specific criteria. An HP D300e Digital Dispenser is used for on-demand production of minimal inhibitory concentration (MIC) panels5 that are used for CLSI reference broth microdilution (BMD) testing of the newest antimicrobial agents. This testing is CLIA compliant and enables AR Lab Network regional laboratories to perform ExAST with a quick turn-around time.
Based on the current national need, ExAST at the AR Lab Network regional laboratories will offer testing (and reporting as indicated) of MBL-producing isolates of Enterobacteriaceae with the following antimicrobials and antimicrobial combinations:
The report sent back to your laboratory will include a comment similar to the following to help explain the results: “For aztreonam-avibactam, a minimum inhibitory concentration (MIC) is reported without an interpretation because clinical breakpoints for this drug combination have not been established. This drug demonstrates in vitro activity against metallo-β-lactamase (MBL) producing Enterobacteriaceae. Its clinical efficacy is under evaluation in clinical trials. Surveillance data indicate that MICs of MBL-producing isolates of Enterobacteriaceae (n = 580) ranged from ≤ 0.015/4 to 8/4 μg/mL.”
Since this MIC testing has been validated in each of the AR Lab Network regional laboratories performing ExAST, the MIC result with the comment can be reported by the submitting laboratory.
Note: CDC through the AR Lab Network plans to expand testing as new or novel antimicrobial treatment options become available for serious infections caused by multi-drug resistant organisms.
In addition, please note:
*Although these are the basic criteria, exceptions may be made. Suitability for testing will be explored when you contact your AR Lab Network laboratory about a specific isolate/patient.
1 Gilbert DN, Chambers HF, Eliopoulos GM, Saag MS, Pavia AT, et al. The Sanford Guide to Antimicrobial Therapy. 2019. Antimicrobial Therapy, Inc. Sperryville, VA.
2 Marshall S, Hujer AM, Rojas LJ, et al. Can ceftazidime-avibactam and aztreonam overcome β-lactam resistance conferred by metallo-β-lactamases in Enterobacteriaceae? Antimicrob Agents Chemother. 2017;61(4):e02243-16.
3 Biedenback DJ, Kazmierczak K, Bouchillon SK, et al. In vitro activity of aztreonam-avibactam against a global collection of gram-negative pathogens from 2012 and 2013. Antimicrob Agents Chemother. 2015. 59(7): 4239-4248.
4 Centers for Disease Control and Prevention. Antibiotic/Antimicrobial resistance (AR/AMR), Laboratory Testing and Resources. https://www.cdc.gov/drugresistance/laboratories.html. Accessed May 21, 2019.
5 Smith KP, Kirby JE. Verification of an automated, digital dispensing platform for at-will broth microdilution-based antimicrobial susceptibility testing. J Clin Microbiol. 2016;54(9):2288-2293.
This article came from AST News Update, Volume . 4, Issue 2 – June 2019 which is produced by the CLSI Outreach Working Group (ORWG). The ORWG is part of the CLSI Subcommittee on Antimicrobial Susceptibility Testing (AST) and was established in 2015. The formation of the working group originated in a desire to efficiently convey information regarding contemporary AST practices, recommendations, and resources to the clinical microbiology community. They welcome suggestions from you about any aspect of CLSI documents, educational materials, or their Newsletters.