Objectives Recent reports indicate the emergence of a new carbapenemase-producing Klebsiella pneumoniae clone, ST307. We sought to better understand the global epidemiology and evolution of this clone and evaluate its association with antimicrobial resistance (AMR) genes. Methods We collated information from the literature and public databases and performed a comparative analysis of 95 ST307 genomes (including 37 that were newly sequenced). Results We show that ST307 emerged in the mid-1990s (nearly 20 years prior to its first report), is already globally distributed and is intimately associated with a conserved plasmid harbouring the bla CTX-M-15 ESBL gene and several other AMR determinants. Conclusions Our findings support the need for enhanced surveillance of this widespread ESBL clone in which carbapenem resistance has occasionally emerged.

Background The clonal diversity underpinning trends in multidrug resistant Escherichia coli causing bloodstream infections remains uncertain. We aimed to determine the contribution of individual clones to resistance over time, using large-scale genomics-based molecular epidemiology.Methods This was a longitudinal, E coli population, genomic, cohort study that sampled isolates from 22 512 E coli bloodstream infections included in the Norwegian surveillance programme on resistant microbes (NORM) from 2002 to 2017. 15 of 22 laboratories were able to share their isolates, and the first 22•5% of isolates from each year were requested. We used whole genome sequencing to infer the population structure (PopPUNK), and we investigated the clade composition of the dominant multidrug resistant clonal complex (CC)131 using genetic markers previously reported for sequence type (ST)131, effective population size (BEAST), and presence of determinants of antimicrobial resistance (ARIBA, PointFinder, and ResFinder databases) over time. We compared these features between the 2002-10 and 2011-17 time periods. We also compared our results with those of a longitudinal study from the UK done between 2001 and 2011. FindingsOf the 3500 isolates requested from the participating laboratories, 3397 (97•1%) were received, of which 3254 (95•8%) were successfully sequenced and included in the analysis. A significant increase in the number of multidrug resistant CC131 isolates from 71 (5•6%) of 1277 in 2002-10 to 207 (10•5%) of 1977 in 2011-17 (p<0•0001), was the largest clonal expansion. CC131 was the most common clone in extended-spectrum β-lactamase (ESBL)-positive isolates (75 [58•6%] of 128) and fluoroquinolone non-susceptible isolates (148 [39•2%] of 378). Within CC131, clade A increased in prevalence from 2002, whereas the global multidrug resistant clade C2 was not observed until 2007. Multiple de-novo acquisitions of both bla CTX-M ESBL-encoding genes in clades A and C1 and gain of phenotypic fluoroquinolone non-susceptibility across the clade A phylogeny were observed. We estimated that exponential increases in the effective population sizes of clades A, C1, and C2 occurred in the mid-2000s, and in clade B a decade earlier. The rate of increase in the estimated effective population size of clade A (N e =3147) was nearly ten-times that of C2 (N e =345), with clade A over-represented in Norwegian CC131 isolates (75 [27•0%] of 278) compared with the UK study (8 [5•4%] of 147 isolates).Interpretation The early and sustained establishment of predominantly antimicrobial susceptible CC131 clade A isolates, relative to multidrug resistant clade C2 isolates, suggests that resistance is not necessary for clonal success. However, even in the low antibiotic use setting of Norway, resistance to important antimicrobial classes has rapidly been selected for in CC131 clade A isolates. This study shows the importance of genomic surveillance in uncovering the complex ecology underlying multidrug resistance dissemination and competition, which have impl...

Background MDR and hypervirulence (hv) are typically observed in separate Klebsiella pneumoniae populations. However, convergent strains with both properties have been documented and potentially pose a high risk to public health in the form of invasive infections with limited treatment options. Objectives Our aim was to characterize the genetic determinants of virulence and antimicrobial resistance (AMR) in two ESBL-producing K. pneumoniae isolates belonging to the international MDR clone ST15. Methods The complete genome sequences of both isolates, including their plasmids, were resolved using Illumina and Oxford Nanopore sequencing. Results Both isolates carried large mosaic plasmids in which AMR and virulence loci have converged within the same vector. These closely related mosaic hv-MDR plasmids include sequences typical of the K. pneumoniae virulence plasmid 1 (KpVP-1; including aerobactin synthesis locus iuc ) fused with sequences typical of IncFII K conjugative AMR plasmids. One hv-MDR plasmid carried three MDR elements encoding the ESBL gene bla CTX-M-15 and seven other AMR genes ( bla TEM , aac3'-IIa , dfrA1 , satA2 , bla SHV , sul1 and aadA1 ) . The other carried remnants of these elements encoding bla TEM and aac3'-IIa , and bla CTX-M-15 was located in a second plasmid in this isolate. The two isolates originated from patients hospitalized in Norway but have epidemiological and genomic links to Romania. Conclusions The presence of both virulence and AMR determinants on a single vector enables simultaneous transfer in a single event and potentially rapid emergence of hv-MDR K. pneumoniae clones. This highlights the importance of monitoring for such convergence events with stringent genomic surveillance.

Infants may be long-term faecal carriers of ESBL-producing K. pneumoniae after colonization during hospitalization in the neonatal period. Delivery by caesarean section and antibiotic treatment during hospitalization are possible risk factors for prolonged carriage. Faecal ESBL carriage in infants represents a reservoir for intra-household spread of ESBL-producing K. pneumoniae.

Neonatal intensive care units (NICUs) are vulnerable to nosocomial outbreaks caused by multiresistant Enterobacteriaceae, but no reports of NICU outbreaks of extended‐spectrum β‐lactamase (ESBL) producing Klebsiella pneumoniae have previously been published from countries with a low level of antimicrobial resistance such as the Scandinavian countries. We describe a clonal outbreak of CTX‐M‐15 ‐producing Klebsiella pneumoniae affecting 58 infants in the neonatal intensive care unit at Stavanger University Hospital, Norway, during a period of 4 months, 2008–2009. The clone spread widely and rapidly in the NICU, and extensive interventions were required to terminate the outbreak. In contrast to previous outbreaks, only one infant acquired a systemic infection caused by the outbreak strain, probably due to a favourable epidemic strain lacking the most common virulence factors. A probable index case was identified, due to multiple positive breast milk samples collected from the infant's mother before and after the infant's transfer from another hospital. Breast milk samples from 3/18 (17%) mothers of colonized infants were positive for ESBL‐producing K. pneumoniae. Vertical transmission of ESBL‐producing bacteria has been shown previously,’but the possibility of transmission of ESBL‐producing K. pneumoniae through expressed breast milk is reported here for the first time. The increasing occurrence of ESBL‐producing’Enterobacteriaceae should therefore encourage changes in diagnostic routines for bacterial screening of breast milk.