KPC-producing Escherichia coli (KPC-Ec) remains uncommon, being mainly reported as the cause of sporadic episodes of infection rather than outbreak events. Here we retrospectively describe the dynamics of a large hospital outbreak sustained by KPC-Ec, involving 106 patients and 25 hospital wards, during a six-month period. Twenty-nine representative KPC-Ec isolates (8/29 from rectal swabs; 21/29 from other clinical specimens) have been investigated by Whole-Genome Sequencing (WGS). Outbreak isolates showed a multidrug-resistant profile and harbored several resistance determinants, including blaCTX-M-27, aadA5, dfrA17, sulI, gyrA1AB and parC1aAB. Phylogenomic analysis identified the ST131 cluster 1 (23/29 isolates), H30Rx clade C, as responsible for the epidemic event. A further two KPC-Ec ST131 clusters were identified: cluster 2 (n = 2/29) and cluster 3 (n = 1/29). The remaining KPC-Ec resulted in ST978 (n = 2/29) and ST1193 (n = 1/29), and were blaKPC-3 associated. The KPC-Ec ST131 cluster 1, originated in a previous KPC-Kp endemic context probably by plasmid transfer, and showed a clonal dissemination strategy. Transmission of the blaKPC gene to the globally disseminated high-risk ST131 clone represents a serious cause of concern. Application of WGS in outbreak investigations could be useful to better understand the evolution of epidemic events in order to address infection control and contrast interventions, especially when high-risk epidemic clones are involved.

Biomedical Center Faculty of Medicine in Pilsen Charles University 323 00 Pilsen Czech Republic

Clinical Pathology and Microbiology Unit S Giovanni di Dio Hospital 88900 Crotone Italy

Department of Clinical Surgical Diagnostic and Pediatric Sciences Unit of Microbiology and Clinical Microbiology University of Pavia 27100 Pavia Italy

Microbiology and Virology Unit A Manzoni Hospital 23900 Lecco Italy

Romeo and Enrica Invernizzi Pediatric Research Center Department of Biomedical and Clinical Sciences L Sacco University of Milan 20157 Milan Italy

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