Detection, Identification, and Susceptibility Testing of CRE

Clinically relevant members of the Enterobacterales are frequently isolated in the laboratory from a variety of sources. It is very important to accurately detect CRE in order to properly treat patients and prevent the spread of MDROs.

The best way to detect CRE is to ensure the use of current breakpoints in antimicrobial susceptibility testing (AST). With commercial AST systems, contact the manufacturer to verify the breakpoint status used. When using the current Clinical and Laboratory Standards Institute (CLSI) AST breakpoints, carbapenemase-producing Enterobacterales (CPE) will usually test intermediate to resistant to one or more of the carbapenems. They further note that of the carbapenems, ertapenem nonsusceptibility is the most sensitive indicator of carbapenemase production.

The most recent edition of the Clinical and Laboratory Standards Institute (CLSI) Performance Standards for Antimicrobial Susceptibility Testing document M100 provides the most up-to-date carbapenem zone diameter and MIC breakpoint guidelines for Enterobacterales.

The most current Food and Drug Administration (FDA) breakpoints are available at: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm575163.htm.

Detecting the presence of carbapenemase in CRE is not recommended for routinely guiding patient therapy, as long as the most current AST breakpoints are being used. However, there may be facility infection control procedures or epidemiological reasons that may warrant detecting the presence of carbapenemase, including when a CRE outbreak is suspected or in an effort to gain a better understanding of emerging resistance patterns. Tests to detect the presence of carbapenemase in Enterobacterales (as well as Pseudomonas aeruginosa and Acinetobacter species) include the modified Hodge test (MHT), CarbaNP test (CNPt), carbapenem inactivation method (CIM), and various molecular methods. There is not a single phenotypic carbapenemase method that will detect all carbapenemases. It is critical to consult the most recent guidelines due to the rapidly changing resistance mechanisms present in Enterobacterales.