Emergence and dissemination of antimicrobial resistance in Escherichia coli causing bloodstream infections in Norway in 2002-17: a nationwide, longitudinal, microbial population genomic study.

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. FINDINGS: Of 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 ß-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 blaCTX-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 (Ne=3147) was nearly ten-times that of C2 (Ne=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 implications for the design of strategies and interventions to control the spread of high-risk multidrug resistant clones. FUNDING: Trond Mohn Foundation, European Research Council, Marie Sklodowska-Curie Actions, and the Wellcome Trust.

Trends in antimicrobial resistance and empiric antibiotic therapy of bloodstream infections at a general hospital in Mid-Norway: a prospective observational study.

BACKGROUND: The occurrence of bloodstream infection (BSI) and antimicrobial resistance have been increasing in many countries. We studied trends in antimicrobial resistance and empiric antibiotic therapy at a medium-sized general hospital in Mid-Norway. METHODS: Between 2002 and 2013, 1995 prospectively recorded episodes of BSI in 1719 patients aged 16-99 years were included. We analyzed the antimicrobial non-susceptibility according to place of acquisition, site of infection, microbe group, and time period. RESULTS: There were 934 community-acquired (CA), 787 health care-associated (HCA) and 274 hospital-acquired (HA) BSIs. The urinary tract was the most common site of infection. Escherichia coli was the most frequently isolated infective agent in all three places of acquisition. Second in frequency was Streptococcus pneumoniae in CA and Staphylococcus aureus in both HCA and HA. Of the BSI microbes, 3.5% were non-susceptible to the antimicrobial regimen recommended by the National Professional Guidelines for Use of Antibiotics in Hospitals, consisting of penicillin, gentamicin, and metronidazole (PGM). In contrast, 17.8% of the BSI microbes were non-susceptible to cefotaxime and 27.8% were non-susceptible to ceftazidime. Antimicrobial non-susceptibility differed by place of acquisition. For the PGM regimen, the proportions of non-susceptibility were 1.4% in CA, 4.8% in HCA, and 6.9% in HA-BSI (p < 0.001), and increasing proportions of non-susceptibility over time were observed in HA-BSI, 2.2% in 2002-2005, 6.2% in 2006-2009, and 11.7% in 2010-2013 (p = 0.026), mainly caused by inherently resistant microbes. We also observed increasing numbers of bacteria with acquired resistance, particularly E. coli producing ESBL or possessing gentamicin resistance, and these occurred predominantly in CA- and HCA-BSI. CONCLUSIONS: Generally, antimicrobial resistance was a far smaller problem in our BSI cohort than is reported from countries outside Scandinavia. In our cohort, appropriate empiric antibiotic therapy could be achieved to a larger extent by replacing second- and third-generation cephalosporins with penicillin-gentamicin or piperacillin-tazobactam.

Infectious tenosynovitis with bloodstream infection caused by Erysipelothrix rhusiopathiae, a case report on an occupational pathogen.

BACKGROUND: Erysipelothrix rhusiopathiae is an established animal pathogen, which may cause infections in humans. It is a gram-positive rod and found in the tonsils or the digestive tracts of animals. The bacterium is occupationally related, as usually only people with frequent animal contacts are infected. We report a case of a patient who was admitted with an infectious tenosynovitis with bloodstream infection due to E. rhusiopathiae, and to our knowledge, this is the first report of a tenosynovitis with systemic manifestation associated with this bacterium. CASE PRESENTATION: A 52-year old Norwegian man, who worked with transportation of swine cadavers, was admitted to the local hospital with sepsis and unknown focus of infection. A few days earlier he had an injury to the skin of one of his fingers that later proved to be infected with E. rhusiopathiae. There were no other causes for his symptoms than the infectious tenosynovitis with systemic manifestation. The infection resolved on treatment with antibiotics and surgery. A transoesophageal echocardiogram was performed to exclude endocarditis, which may be associated with this pathogen. CONCLUSIONS: This case report highlights the importance of clinicians being aware of this bacterium, and we describe risk factors for infection, differences in the clinical manifestations of the disease, challenges with diagnosing the bacterium and adverse effects of immunosuppressive drugs. Recommended treatment is appropriate antibiotic therapy and adequate debridement and surgical drainage of the tendon sheath.