THE CARBAPENEMASE PRODUCING CARBAPENEM-RESISTANT ENTEROBACTERIACEAE (CP-CRE) GENE DISTRIBUTION IN MALAYSIA (2016 – 2021): A REPORT

Abstract

Intro: Carbapenemase producing carbapenem-resistant enterobacteriaceae (CP- CRE) has been an emerging issue for the past decade. The horizontal gene transfer via plasmids contributes to the widespread dissemination of CP-CRE. Here, we demonstrate the distribution of CP-CRE genes from enterobacteriaceae isolates in Malaysia from 2016 - 2021. Methods: Enterobacteriaceae isolated from patients in Malaysian Healthcare centers confirmed as CP-CRE based on the Clinical and Laboratory Standards Institute (CLSI) described methods (carbapenem MICs, modified Hodge test, mCIM and/or eCIM) and breakpoints were sent to the Institute for Medical Research (IMR) for PCR confirmation. Five CRE genes (NDM, OXA, KPC, IMP, and VIM) were screened using multiplex PCR. Findings: A total of 10,999 samples were processed from 2016 – 2021 with a median of 1659 (174). A Chi-Square Goodness of Fit Test determined the number of isolates received in 2021 differ significantly as compared to previous years (x2 (5)=646, p<0.01) which skewed the distribution but did not differ in the percentage of positive samples (x2(5)=1.9, p=.86). On average, about 77.5% isolates tested will carry at least one CP-CRE gene yearly and the most common positive organism is Klebsiella spp. (63.8%), followed by Enterobacter spp. (12.2%) and Escherichia spp. (11.5%). Overall, the NDM gene was most prevalent (83.6%) (x2 (25)=198.2, p<0.01) followed by OXA (10.8%), IMP (1.5%), KPC and VIM (0.3% respectively). The remaining 3.5% isolates carry more than one CP-CRE gene, with 98.6% of such isolates carrying two genes and 1.3% carrying three genes. The NDM+OXA gene combination is the most common (89.4%) among all gene combinations yearly. Conclusion: The prevalence of CP-CRE continues to rise with increasing healthcare burden. Multigene CP-CRE organisms continue to be a rare, but worrying entity. Continued surveillance and further studies is imperative in order to curb this issue.