A nationwide genomic study of clinical <i>Klebsiella pneumoniae</i> in Norway 2001–15: introduction and spread of ESBLs facilitated by clonal groups CG15 and CG307

Fostervold, Aasmund; Hetland, Marit Andrea Klokkhammer; Bakksjø, Ragna; Bernhoff, Eva; Holt, Kathryn E.; Samuelsen, Ørjan; Simonsen, Gunnar Skov; Sundsfjord, Arnfinn; Löhr, Iren Høyland; Lindemann, Paul Christoffer; Handal, Nina; Rødland, Åshild Marvik; Jakovljev, Aleksandra; Åsheim, Sandra; Gammelsrud, Karianne Wiger; Sandnes, Rolf Arne; Weme, Einar Tollaksen; Kümmel, Angela; Nilsen, Einar; Lindstad, Belinda Langnes; Hollekim, Anne C; Hjetland, Reidar; Oseid, Anne R; Hafne, Liv Jorunn

doi:10.1093/jac/dkab463

Cited by 19 publications

(28 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, aerobactin was detected in only 7 (2 of which were iuc3) out of 484 intestinal K. pneumoniae isolates from healthy humans in Norway (1.4 %) [52]. Another Norwegian study has described the finding of iuc3 in K. pneumoniae from two humans with bloodstream infections [54]. A blast search identified the composite transposon sequences in these two isolates, as well as in K. pneumoniae isolates from China, Thailand, the UK, the USA and Laos, mostly from pigs and humans.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Highly conserved composite transposon harbouring aerobactin iuc3 in Klebsiella pneumoniae from pigs

et al. 2023

Self Cite

View full text Add to dashboard Cite

Klebsiella pneumoniae is an important opportunistic pathogen associated with severe invasive disease in humans. Hypervirulent K. pneumoniae , which are K. pneumoniae with several acquired virulence determinants such as the siderophore aerobactin and others, are more prominent in countries in South and South-East Asia compared to European countries. This Klebsiella pathotype is capable of causing liver abscesses in immunocompetent persons in the community. K. pneumoniae has not been extensively studied in non-human niches. In the present study, K. pneumoniae isolated from caecal samples (n=299) from healthy fattening pigs in Norway were characterized with regard to population structure and virulence determinants. These data were compared to data from a previous study on K. pneumoniae from healthy pigs in Thailand. Lastly, an in-depth plasmid study on K. pneumoniae with aerobactin was performed. Culturing and whole-genome sequencing was applied to detect, confirm and characterize K. pneumoniae isolates. Phylogenetic analysis described the evolutionary relationship and diversity of the isolates, while virulence determinants and sequence types were detected with Kleborate. Long-read sequencing was applied to obtain the complete sequence of virulence plasmids harbouring aerobactin. A total of 48.8 % of the investigated Norwegian pig caecal samples (n=299) were positive for K. pneumoniae . Acquired virulence determinants were detected in 72.6 % of the isolates, the most prominent being aerobactin (69.2 %), all of which were iuc3. In contrast, only 4.6 % of the isolates from Thailand harboured aerobactin. The aerobactin operon was located on potentially conjugative IncFIBK/FIIK plasmids of varying sizes in isolates from both countries. A putative, highly conserved composite transposon with a mean length of 16.2 kb flanked by truncated IS3-family IS407-group insertion sequences was detected on these plasmids, harbouring the aerobactin operon as well as several genes that may confer increased fitness in mammalian hosts. This putative composite transposon was also detected in plasmids harboured by K. pneumoniae from several countries and sources, such as human clinical samples. The high occurrence of K. pneumoniae harbouring aerobactin in Norwegian pigs, taken together with international data, suggest that pigs are a reservoir for K. pneumoniae with iuc3. Truncation of the flanking ISKpn78-element suggest that the putative composite transposon has been permanently integrated into the plasmid, and that it is no longer mobilizable.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Another Norwegian study has described the finding of iuc3 in K. pneumoniae from two humans with bloodstream infections [54]. A blast search identified the composite transposon sequences in these two isolates, as well as in K.…”

Section: Discussionmentioning

confidence: 99%

Highly conserved composite transposon harbouring aerobactin iuc3 in Klebsiella pneumoniae from pigs

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“… 29 Fostervold et al observed a higher prevalence of the yersiniabactin gene in extended-spectrum β-lactamase (ESBL) (37.8%) than in the non-ESBL (17.3%) Kp isolates. 30 Another study reported that genes encoding yersiniabactin were identified in 83.7% (123/147) of the CRKP isolates. 31 Sherif et al found that yersiniabactin was the most common virulence factor (69.2%) in 39 randomly selected, geographically diverse MDR Kp isolates.…”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes, Microbiological Characteristics and Risk Factors for Difficult-to-Treat Resistance to Klebsiella pneumoniae Infection

Yang¹,

Liu²,

Wu³

et al. 2022

IDR

View full text Add to dashboard Cite

Purpose This study aimed to identify the clinical outcomes, microbiological features and risk factors for difficult-to-treat resistance (DTR) Klebsiella pneumoniae (Kp) infection. Materials and Methods A retrospective study was conducted at Peking University Third Hospital from January 2020 to March 2021. DTR was defined as resistance to ≥1 carbapenem, ≥1 extended-spectrum cephalosporin, and ≥1 fluoroquinolone. Hypervirulent Kp (HvKp) was defined as peg-344-, iroB-, iucA-, rmpA- , or rmpA2 -positive. Clinical data were collected. Antimicrobial susceptibility testing and string tests were performed to determine resistance and hypermucoviscosity phenotype. Whole genome sequencing was performed to analyze the sequence type (ST), capsular serotypes, resistance and virulence genes. Risk factors for 30-day mortality were analyzed. Results Fifty DTR-Kp (50.0%) strains were identified among 100 patients. Compared to non-DTR-Kp group, a significant number of patients with DTR-Kp infection experienced ICU admission (44.0% versus 10.0%, P<0.001) and mechanical ventilation after Kp detection (26.0% versus 10.0%, P=0.037). Notably, the percentage of hvKp among the DTR-Kp isolates increased consistently over the 15 months evaluated. Most DTR-Kp strains belonged to ST11 (82.0%), followed by ST15 (12.0%), ST86 (2.0%), ST996 (2.0%), and ST3157 (2.0%). DTR-Kp isolates possessed various resistance genes, such as bla KPC-2 , bla TEM-1D and fosA3 (90.0%, 80.0% and 72.0%, respectively). Importantly, the yersiniabactin genes were significantly clustered in DTR group (48/50, 96.0%). The 30-day mortality was significantly higher in patients with DTR-Kp infection than non-DTR-Kp group (38.0% versus 8.2%, P=0.001). DTR-Kp infection (odds ratio [OR] = 4.196) was an independent risk factor for the 30-day mortality of Kp-infected patients. Additionally, cerebrovascular disease (OR = 2.780) and Charlson comorbidity index (OR= 1.584) were independent risk factors for DTR-Kp infections. Conclusion DTR-hvKp is rapidly emerging. The DTR-Kp strains harbored various resistance genes and high rates of yersiniabactin siderophore genes. DTR-Kp infection was an independent risk factor for mortality, suggesting that enhanced awareness essential.

show abstract

“…Those that were confirmed ST17 and had <500 assembled contigs, known year of collection and sample source (n=149) were included in our global dataset. Additionally, we included 64 ST17 genomes from the recent SpARK study (17) and 41 ST17 genomes from Norwegian surveillance studies that were not linked to the Stavanger NICU outbreak (11, 21–23). For analyses of global dynamics, we also included 46 of the Stavanger NICU outbreak genomes, resulting in a global dataset of 300 genomes (BioSample accessions are given in Table S2).…”

Section: Methodsmentioning

confidence: 99%

Within-patient and global evolutionary dynamics ofKlebsiella pneumoniaeST17

Hetland

Hawkey

Bernhoff

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Klebsiella pneumoniaesequence type (ST) 17 is a global problem clone that causes multidrug-resistant (MDR) hospital infections worldwide. In 2008-2009, an outbreak of MDR ST17 occurred at a neonatal intensive care unit (NICU) in Stavanger, Norway. Fifty-seven children were colonised. We observed intestinal persistence of ST17 in all of the children for up to two years after hospital discharge. Here, we investigated the within-host evolution of ST17 in 45 of those children during long-term colonisation and compared the outbreak with 254 global strains. Ninety-two outbreak-related isolates were whole-genome sequenced. They had capsule locus KL25, O locus O5 and carried yersiniabactin. During within-host colonisation ST17 remained stable with few single nucleotide polymorphisms, no acquisition of antimicrobial resistance (AMR) or virulence determinants, and persistent carriage of ablaCTX-M-15-encoding IncFII(K) IncFIB(K) plasmid (pKp2177_1). The global collection included ST17 from 1993-2020 from 34 countries, that were from human infection (41.3%), colonisation (39.3%) and respiratory specimens (7.3%), from animals (9.3%), and from the environment (2.7%). We estimate that ST17 emerged mid-to-late 19th century (1859, 95% HPD 1763-1939) and diversified through recombinations of the K and O loci to form several sublineages, with various AMR genes, virulence loci and plasmids. There was limited evidence of persistence of AMR genes in any of these lineages. A globally disseminated sublineage with KL25/O5 accounted for 52.7% of the genomes. It included a monophyletic subclade that emerged in the mid-1980s, which comprised the Stavanger NICU outbreak and 10 genomes from three other countries, which all carried pKp2177_1. The plasmid was also observed in a KL155/OL101 subclade from the 2000s. Three clonal expansions of ST17 were identified, all were healthcare-associated and carried either yersiniabactin and/or pKp2177_1. To conclude, ST17 is globally disseminated and associated with opportunistic hospital-acquired infections. It contributes to the burden of global MDR infections, but many diverse lineages persist without acquired AMR. We hypothesise that non-human sources and human colonisation may play a crucial role for severe infections in vulnerable patients, such as preterm neonates.

show abstract

A nationwide genomic study of clinical Klebsiella pneumoniae in Norway 2001–15: introduction and spread of ESBLs facilitated by clonal groups CG15 and CG307

Cited by 19 publications

References 42 publications

Highly conserved composite transposon harbouring aerobactin iuc3 in Klebsiella pneumoniae from pigs

Highly conserved composite transposon harbouring aerobactin iuc3 in Klebsiella pneumoniae from pigs

Clinical Outcomes, Microbiological Characteristics and Risk Factors for Difficult-to-Treat Resistance to Klebsiella pneumoniae Infection

Within-patient and global evolutionary dynamics ofKlebsiella pneumoniaeST17

Contact Info

Product

Resources

About