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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...

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Increasing incidence rates of invasive Streptococcus dysgalactiae subspecies equisimilis (SDSE) infections have been reported worldwide, but the evolutionary mechanisms underlying this development remain elusive. Through prospective surveillance of invasive SDSE infections in western Norway, we observed the emergence of a novel and virulent SDSE genotype, stG62647. This emm-type, rarely encountered as a cause of invasive disease during 1999–2012, emerged in 2013 as the predominant SDSE-genotype. The stG62647-infections were associated with an aggressive clinical course, including the occurrence of streptococcal toxic shock syndrome, necrotizing soft-tissue infections and endocarditis. All the invasive stG62647-isolates were subjected to whole genome sequencing, attempting to explore the genetic events underpinning its epidemicity. Although 10% of the genomes was unique for stG62647-genotype, notably 18 out of 19 isolates contained a disrupted streptococcal invasive locus (sil) due to the insertion of a transposase, IS1548, into the silB-gene. We postulate that the virulence of stG6267-isolates could be partly attributable to the abrogation of the attenuating control normally exerted by this regulon, although experimental verification was not performed. To the best of our knowledge, this is the first study employing large scale whole genome sequencing to illuminate the genetic landscape of epidemic lineages in SDSE.

Resistance to gentamicin in Escherichia coli from blood culture has shown an increase over the past decade in Norway. This study was done to investigate aminoglycoside resistance in Escherichia coli and Klebsiella pneumoniae in Western Norway. The material included 49 blood culture isolates which had shown aminoglycoside resistance collected during 2000-2009. To investigate co-resistance to alternative antibiotics and dynamics involved in aminoglycoside resistance 67 isolates (mostly from urine) exhibiting resistance to both aminoglycosides and extended spectrum beta-lactam antibiotics were also included. MIC values were obtained for amikacin, gentamicin, kanamycin, netilmicin, streptomycin and tobramycin and all isolates were screened using PCR for aac(3)-II and aac(6')-Ib, encoding aminoglycoside modifying enzymes. Resistance to ≥3 aminoglycosides was found in 92% of the isolates and 60.3% showed resistance to gentamicin, netilmicin, tobramycin and kanamycin. Amikacin resistance was low. Co-resistance to ciprofloxacin was found in 88% of the isolates with gentamicin resistance. aac(3)-IIa/c was found in 79.3% and aac(6')-Ib in 37.9% of the isolates and 28.4% harboured both genes. aac(6')-Ib-cr, possibly contributing to ciprofloxacin resistance was found mostly in extended spectrum beta-lactamase producers. The aminoglycoside resistance patterns indicate co-existence of multiple resistance mechanisms. The use of ciprofloxacin and third generation cephalosporins is likely to have contributed to the increase in aminoglycoside resistance in Norway.