Performance of mCIM/eCIM in Enterobacterales strains co-encoding NDM and OXA-48-like carbapenemases from South India

ABSTRACT Carbapenem-resistant Enterobacterales (CRE) are an increasing public health concern, particularly as carbapenemase-producing isolates, such as NDM and OXA-48-like producers, become more prevalent. Rapid and accurate identification of carbapenemases is crucial to guide appropriate antibiotic therapy. Although recent epidemiologic data show that CRE increasingly harbor multiple carbapenemases, the performance of common phenotypic tests—the modified carbapenem inactivation method (mCIM) and EDTA-modified CIM (eCIM)—has not been well defined in these isolates. We examined the performance of mCIM and eCIM among CRE-encoding NDM, OXA-48-like, or both. We included 172 genotypically confirmed carbapenemase-encoding CRE isolates from perirectal swabs collected from patients admitted to two intensive care units at a hospital in South India. Isolates included Escherichia coli (53.5%), Klebsiella pneumoniae (41.3%), and Enterobacter species (5.3%). Overall, 112 isolates (65.1%) encoded NDM alone, 23 (13.4%) encoded OXA-48-like alone, and 37 (21.5%) encoded both NDM and OXA-48-like. mCIM positivity was 98.2% for NDM, 47.8% for OXA-48-like, and 94.6% for NDM+OXA-48-like encoders; among mCIM-positive isolates, eCIM positivity rates were 99.1%, 91%, and 97.1%, respectively. When compared to molecular carbapenemase gene detection, mCIM/eCIM was highly sensitive for classifying isolates encoding NDM as metallo-β-lactamase (MBL) producers, but significantly misclassified isolates encoding OXA-48-like as having an MBL or lacking a carbapenemase. In the largest collection of NDM and OXA-48-like co-encoding CRE isolates to date, mCIM/eCIM typically reported these as MBL producers. IMPORTANCE Carbapenemase-encoding Enterobacterales infections are associated with substantial adverse health outcomes, making rapid and accurate carbapenemase detection essential for guiding antibiotic therapy. Although Enterobacterales carrying multiple carbapenemases are increasingly reported worldwide, the performance of common phenotypic assays, mCIM and eCIM, remains insufficiently defined for these strains. In this study of 172 genotypically confirmed carbapenemase-encoding Enterobacterales isolates from hospitalized patients in South India, mCIM/eCIM consistently classified NDM-encoding isolates as metallo-β-lactamase encoders. Additionally, mCIM/eCIM frequently misclassified OXA-48-like-encoding isolates as either metallo-β-lactamase encoders or carbapenemase-negative, highlighting the need to better understand the mechanisms underlying this variable activity. In the largest collection of NDM and OXA co-encoding Enterobacterales isolates reported to date, mCIM/eCIM generally reported co-encoding isolates as metallo-β-lactamase producers. Our results suggest that mCIM/eCIM performance may vary geographically due to variable activity, distribution, and combinations of carbapenemases.