Anette M Hammerum1, Frank Hansen2, Hans Linde Nielsen3, Lotte Jakobsen2, Marc Stegger2,4, Paal S Andersen2,4,5, Paw Jensen6, Tue Kjærgaard Nielsen7, Lars Hestbjerg Hansen7, Henrik Hasman2, David Fuglsang-Damgaard3. 1. Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark ama@ssi.dk. 2. Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark. 3. Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark. 4. Pathogen Genomics Division, Translational Genomics Research Institute (TGen), Flagstaff, AZ, USA. 5. Veterinary Disease Biology, University of Copenhagen, Copenhagen, Denmark. 6. Department of Haematology, Aalborg University Hospital, Aalborg, Denmark. 7. Department of Environmental Science, Aarhus University, Roskilde, Denmark.
Abstract
OBJECTIVES: An outbreak of NDM-1-producing Citrobacter freundii and possible secondary in vivo spread of blaNDM-1 to other Enterobacteriaceae were investigated. METHODS: From October 2012 to March 2015, meropenem-resistant Enterobacteriaceae were detected in 45 samples from seven patients at Aalborg University Hospital, Aalborg, Denmark. In silico resistance genes, Inc plasmid types and STs (MLST) were obtained from WGS data from 24 meropenem-resistant isolates (13 C. freundii, 6 Klebsiella pneumoniae, 4 Escherichia coli and 1 Klebsiella oxytoca) and 1 meropenem-susceptible K. oxytoca. The sequences of the meropenem-resistant C. freundii isolates were compared by phylogenetic analyses. In vitro susceptibility to 21 antimicrobial agents was tested. Furthermore, in vitro conjugation and plasmid characterization was performed. RESULTS: From the seven patients, 13 highly clonal ST18 NDM-1-producing C. freundii were isolated. The ST18 NDM-1-producing C. freundii isolates were only susceptible to tetracycline, tigecycline, colistin and fosfomycin (except for the C. freundii isolates from Patient 2 and Patient 7, which were additionally resistant to tetracycline). The E. coli and K. pneumoniae from different patients belonged to different STs, indicating in vivo transfer of blaNDM-1 in the individual patients. This was further supported by in vitro conjugation and detection of a 154 kb IncA/C2 plasmid with blaNDM-1. Patient screenings failed to reveal any additional cases. None of the patients had a history of recent travel abroad and the source of the blaNDM-1 plasmid was unknown. CONCLUSIONS: To our knowledge, this is the first report of an NDM-1-producing C. freundii outbreak and secondary in vivo spread of an IncA/C2 plasmid with blaNDM-1 to other Enterobacteriaceae.
OBJECTIVES: An outbreak of NDM-1-producing Citrobacter freundii and possible secondary in vivo spread of blaNDM-1 to other Enterobacteriaceae were investigated. METHODS: From October 2012 to March 2015, meropenem-resistant Enterobacteriaceae were detected in 45 samples from seven patients at Aalborg University Hospital, Aalborg, Denmark. In silico resistance genes, Inc plasmid types and STs (MLST) were obtained from WGS data from 24 meropenem-resistant isolates (13 C. freundii, 6 Klebsiella pneumoniae, 4 Escherichia coli and 1 Klebsiella oxytoca) and 1 meropenem-susceptible K. oxytoca. The sequences of the meropenem-resistant C. freundii isolates were compared by phylogenetic analyses. In vitro susceptibility to 21 antimicrobial agents was tested. Furthermore, in vitro conjugation and plasmid characterization was performed. RESULTS: From the seven patients, 13 highly clonal ST18 NDM-1-producing C. freundii were isolated. The ST18 NDM-1-producing C. freundii isolates were only susceptible to tetracycline, tigecycline, colistin and fosfomycin (except for the C. freundii isolates from Patient 2 and Patient 7, which were additionally resistant to tetracycline). The E. coli and K. pneumoniae from different patients belonged to different STs, indicating in vivo transfer of blaNDM-1 in the individual patients. This was further supported by in vitro conjugation and detection of a 154 kb IncA/C2 plasmid with blaNDM-1. Patient screenings failed to reveal any additional cases. None of the patients had a history of recent travel abroad and the source of the blaNDM-1 plasmid was unknown. CONCLUSIONS: To our knowledge, this is the first report of an NDM-1-producing C. freundii outbreak and secondary in vivo spread of an IncA/C2 plasmid with blaNDM-1 to other Enterobacteriaceae.
Authors: Ahmed Babiker; Daniel R Evans; Marissa P Griffith; Christi L McElheny; Mohamed Hassan; Lloyd G Clarke; Roberta T Mettus; Lee H Harrison; Yohei Doi; Ryan K Shields; Daria Van Tyne Journal: J Clin Microbiol Date: 2020-08-24 Impact factor: 5.948