Whole-genome analysis of extensively drug-resistant Enterobacter hormaechei isolated from two hospitalized patients in the United States: A case series of a rare but rising threat

Background New Delhi metallo-beta-lactamases (NDM) confer extensive antibiotic resistance, complicating treatment and leading to poor outcomes. In 2022, two patients at a US academic medical centre in Southeast Michigan were infected with NDM-producing Enterobacter hormaechei. Objective This study describes two NDM-producing E. hormaechei isolates, recovered in 2022 from hospitalized patients at a large academic medical centre in Southeast Michigan. Methods Identification of E. hormaechei and antibiotic susceptibility patterns were determined using MALDI-TOF mass spectrometry and Vitek2® (bioMérieux), respectively, in our clinical microbiology laboratory. Carbapenemase gene detection was performed using Cepheid GeneXpert® (Sunnyvale). Sequencing libraries were created using QIAseq FX DNA Library Kit (Qiagen Sciences Inc.) and sequencing was performed on Illumina NextSeq 2000, respectively. EPISEQ® CS v1.2.0 and 1928 platforms were used for sequencing analysis. Results Two extensively drug-resistant E. hormaechei isolates were recovered from non-urine, non-respiratory sources. Both harboured 25 antimicrobial resistance genes (ARGs), including 13 unique ARGs. Resistance was observed to aminoglycosides [e.g. ant(3’)-Ia, aadA2], beta-lactams (blaACT-17, blaACT-73), broad-spectrum beta-lactams (blaNDM-5), sulphonamides (sul1, sul2), fosfomycin (fosA), glycopeptides (ble) and chlorhexidine (qacE). Isolate 1 carried more ARGs than Isolate 2. Sequence types (ST) for Isolates 1 and 2 were ST93 and ST177, respectively, with ∼88% SNP similarity, indicating non-clonality. Conclusions These findings highlight the clinical significance and genetic diversity of NDM-producing E. hormaechei. Enhanced surveillance, antibiotic stewardship and infection control measures are essential to mitigate the spread of these extensively drug-resistant pathogens.