Genomic analysis of intrahospital transmission of carbapenem-resistant Gram-negative bacteria: a multicentre study in Japan

We aimed to identify genomically defined strain transmission events of carbapenem-resistant Gram-negative bacteria (CRGNB) in hospitals, estimate species-specific transmission rates and identify risk factors for transmission. The study included 708 patients from a Japanese prospective multicentre cohort study, the MultiDrug-Resistant organisms clinical research network, from whom at least one CRGNB isolate was collected between 2019 and 2024 (750 isolates in total). Clinical data were retrieved from electronic medical records, and microbiological analyses were performed at a central reference laboratory. Transmission events were determined via whole-genome sequencing data and single-nucleotide polymorphism-based genomic clustering. We identified 37 genomic clusters associated with intrahospital transmission and 1 associated with interhospital transmission. Ninety-four patients (13%) carried at least one isolate involved in intra-hospital transmission, and each transmission event involved two to six patients. Patients with Acinetobacter spp. (60% involved in intrahospital transmission), Enterobacter cloacae complex (23%) and Klebsiella oxytoca complex (59%) were sig-nificantly associated with intrahospital transmission and were considered high-risk species groups. Patients with Entero-bacterales isolates carrying acquired carbapenemase genes had higher intrahospital transmission rates relative to those without (31% vs. 2%). In multivariable analysis, independent risk factors for patients with intrahospital transmission were overlap in ward and time with other CRGNB-positive patients, carriage of high-risk species groups and acquired carbapen-emase genes. In this Japanese multicentre cohort, intrahospital transmission of CRGNB was associated with both microbiological characteristics and patient-and healthcare-related factors, underscoring the need for targeted surveillance and infection prevention strategies.