Utilizing the Carba NP test as an indicator of expression level of carbapenemase genes in Enterobacteriaceae

•IMP-6 metallo-β-lactamase (MBL)-producing Enterobacteriaceae is usually susceptible to imipenem.•The Carba NP test can detect IMP-6 MBL producers.•Time to positivity in the Carba NP test correlates with the expression of the carbapenemase gene.•Time to positivity in the Carba NP test does not correlate with MIC of imipenem.•The Carba NP test can be used as a screening of carbapenemase gene expression level.

The Carba NP test was developed to detect carbapenemase-producing Enterobacteriaceae, and uses imipenem as the reaction substrate. In Japan, IMP-6 metallo-β-lactamase (MBL) producers, which are usually resistant to meropenem but susceptible to imipenem, and IMP-1 MBL producers, which are usually resistant to both carbapenems are prevalent. We performed the Carba NP test with IMP-6 and IMP-1 MBL producers, and both types were detected by the Carba NP test with high sensitivity. All IMP-1 MBL producers were detected by the Carba NP test, but the minimum inhibitory concentrations (MICs) of imipenem varied from 0.25 to > 32 μg/mL, and the time to positivity varied from 0 to 30 min. Time to positivity was significantly correlated with expression levels of blaIMP-1, but not with MICs of imipenem. These results suggested that the Carba NP test can be used as a screening assay for carbapenemase gene expression levels among producers of the same type of carbapenemase. Using this approach, it is possible to determine whether the carbapenem resistance of each carbapenemase-producing Enterobacteriaceae isolate is primarily due to carbapenemase production, or to another mechanism such as outer membrane impermeability.