WGS Analysis of Staphylococcus warneri Outbreak in a Neonatal Intensive Care Unit

Xiang Zhang,1,* Yu Zhou,2,3,* Lu Fu,4,* Lu Zhou,5 Xiangjun Cheng,6 Wei Zhang,2,3 Zhongming Tan5 1Department of Infection Management, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, People’s Republic of China; 3Sanya Institute of Nanjing Agricultural University, Sanya, Hainan Province, People’s Republic of China; 4Department of Nosocomial Infection Management, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, Jiangsu Province, People’s Republic of China; 5NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu Province, People’s Republic of China; 6Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhongming Tan, NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, No. 172 Jiangsu Road, Gulou District, Nanjing, Jiangsu Province, 210009, People’s Republic of China, Tel +862583759339, Email [email protected] Wei Zhang, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, No. 1 Tongwei Road, Nanjing, Jiangsu Province, 210095, People’s Republic of China, Tel +862584396517, Email [email protected]: Staphylococcus warneri is an opportunistic pathogen responsible for hospital-acquired infections (HAIs). The aim of this study was to describe an outbreak caused by S. warneri infection in a neonatal intensive care unit (NICU) and provide investigation, prevention and control strategies for this outbreak.Methods: We conducted an epidemiological investigation of the NICU S. warneri outbreak, involving seven neonates, staff, and environmental screening, to identify the source of infection. WGS analyses were performed on S. warneri isolates, including species identification, core genome single-nucleotide polymorphism (cgSNP) analysis, pan-genome analysis, and genetic characterization assessment of the prevalence of specific antibiotic resistance and virulence genes.Results: Eight S. warneri strains were isolated from this outbreak, with seven from neonates and one from environment. Six clinical cases within three days in 2021 were linked to one strain isolated from environmental samples; isolates varied by 0– 69 SNPs and were confirmed to be from an outbreak through WGS. Multiple infection prevention measures were implemented, including comprehensive environmental disinfection and stringent protocols, and all affected neonates were transferred to the isolation wards. Following these interventions, no further cases of S. warneri infections were observed. Furthermore, pan-genome analysis results suggested that in human S. warneri may exhibit host specificity.Conclusion: The investigation has revealed that the outbreak was linked to the milk preparation workbench by the WGS. It is recommended that there be a stronger focus on environmental disinfection management in order to raise awareness, improve identification, and prevention of healthcare-associated infections that are associated with the hospital environment.Keywords: Staphylococcus warneri, neonatal intensive care unit, whole-genome sequencing, pan-genome