The changing epidemiology of carbapenemase-producing<i>Klebsiella pneumoniae</i>in Italy: toward polyclonal evolution with emergence of high-risk lineages
Vincenzo Di Pilato, Giulia Errico, Monica Monaco, Tommaso Giani, María Del Grosso, Alberto Antonelli, Sophia David, Erika Lindh, Romina Camilli, David M. Aanensen, Gian María Rossolini, Annalisa Pantosti, Esther Manso, Maria Federica Pedna, M Mungiguerra, Presidio Ospedaliero G Moscati, Adriana Mosca, Francesca Vailati, Richard Aschbacher, Alida Imbriani, P Sartore, Ospedale Civile di Cittadella, Cristina Giraldi, Azienda Ospedaliera di Cosenza, Federica Piana, Patrizia Pecile, Ospedale Careggi, Rosella De Nittis, Beatrice Pini, Ospedale A Manzoni, Paola Mirri, Emanuela Bianchi, A Restelli, Daniela Morelli, Istituto Tumori, Maria Rosaria Catania, A. Barbaro, Paola Bernaschi, Gabriella Parisi, Paola Gualdi, Pier Andrea Dusi, Rosalba Bona, Ospedale S Paolo, Marco Maria D’Andrea, Rossana Cavallo, Paolo Lanzafame, Anna L. Sartor, Stefano Grandesso, Francesca Milano
Abstract
BACKGROUND: Previous studies showed that the epidemic of carbapenem-resistant Klebsiella pneumoniae (CR-KP) observed in Italy since 2010 was sustained mostly by strains of clonal group (CG) 258 producing KPC-type carbapenemases. In the framework of the National Antibiotic-Resistance Surveillance (AR-ISS), a countrywide survey was conducted in 2016 to explore the evolution of the phenotypic and genotypic characteristics of CR-KP isolates. METHODS: From March to July 2016, hospital laboratories participating in AR-ISS were requested to provide consecutive, non-duplicated CR-KP (meropenem and/or imipenem MIC >1 mg/L) from invasive infections. Antibiotic susceptibility was determined according to EUCAST recommendations. A WGS approach was adopted to characterize the isolates by investigating phylogeny, resistome and virulome. RESULTS: Twenty-four laboratories provided 157 CR-KP isolates, of which 156 were confirmed as K. pneumoniae sensu stricto by WGS and found to carry at least one carbapenemase-encoding gene, corresponding in most cases (96.1%) to blaKPC. MLST- and SNP-based phylogeny revealed that 87.8% of the isolates clustered in four major lineages: CG258 (47.4%), with ST512 as the most common clone, CG307 (19.9%), ST101 (15.4%) and ST395 (5.1%). A close association was identified between lineages and antibiotic resistance phenotypes and genotypes, virulence traits and capsular types. Colistin resistance, mainly associated with mgrB mutations, was common in all major lineages except ST395. CONCLUSIONS: This WGS-based survey showed that, although CG258 remained the most common CR-KP lineage in Italy, a polyclonal population has emerged with the spread of the new high-risk lineages CG307, ST101 and ST395, while KPC remained the most common carbapenemase.