The changing epidemiology of carbapenemase-producingKlebsiella pneumoniaein Italy: toward polyclonal evolution with emergence of high-risk lineages

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.

Widespread emergence of OmpK36 loop 3 insertions among multidrug-resistant clones of Klebsiella pneumoniae

“…Our data also confirmed previous reports that this clade likely spread from the USA to Europe and the Middle East (26) where it dominated the resistant KP population in some countries over several years (e.g. Italy and Israel) (18,27). Notably, the ST258/512 phylogeny also suggested that there have been multiple reversion events of L3 insertions, represented by genomes lacking a particular L3 insertion amidst a clade carrying that insertion ( Figure 3B ).…”

“…Several of the L3 insertion acquisition events (most notably of GD) are associated with subsequent clonal expansions. For example, the clade consisting largely of ST512 that encodes a GD insertion became highly successful as evident in the phylogeny and supported by multiple surveillance reports (18,27). Our data also confirmed previous reports that this clade likely spread from the USA to Europe and the Middle East (26) where it dominated the resistant KP population in some countries over several years (e.g.…”

Resistome and virulome accretion in an NDM-1-producing ST147 sublineage of Klebsiella pneumoniae associated with an outbreak in Tuscany, Italy: a genotypic and phenotypic characterisation

“…This endemicity was mostly caused by the successful clonal expansion of a K pneumoniae carbapenemase (KPC)-producing K pneumoniae clone and belonging to clonal complex 258. 5 Within the past decade, clonal complex 258 has been compounded by the emergence of additional KPC-producing K pneumoniae clones (eg, ST307 and ST101), 6 whereas CPE producing other types of carbapenemases (eg, OXA-48 and metalloβ-lactamases) have remained sporadic or at most been responsible for small outbreaks. 7 Since November 2018, however, a large outbreak of CPE-producing NDM-type carba penemases (NDM-CPE) emerged in Tuscany, Italy.…”

A Patient With Multiple Carbapenemase Producers Including an Unusual Citrobacter sedlakii Hosting an IncC blaNDM-1- and armA-carrying Plasmid

“…However, p3347689I_1 was missing the IS CR1-aph(3 ' )-VI -IS Aba125-bla NDM-1 -Δ ble- qacEΔ1-sul1 region, suggesting an acquisition event in p3347558_1 ( Figure 1B ). Finally, we note that ST395 is a globally successful lineage that usually carries bla OXA-48 and bla KPC carbapenemase encoding-genes [ 25 ].…”