Jørgen Vildershøj Bjørnholt

• Lindstrøm, Jonas Christoffer; Gjerdrum, Hilde Synnøve Vollan; Brynildsrud, Ola Brønstad; Tannæs, Tone Møller; Kristoffersen, Anja Bråthen & Ricanek, Petr [Show all 17 contributors for this article] (2026). Exploring alterations in the gut resistome in medically treated inflammatory bowel disease patients. BMC Microbiology. 26, p. 1–13. doi: 10.1186/s12866-026-05101-9. Full text in Research Archive
• Vikedal, Krister; Jimenez, Natalia Berges; Riisnæs, Ida Mathilde Marstein; Ræder, Synnøve Brandt; Bjørnholt, Jørgen Vildershøj & Bjørås, Magnar [Show all 9 contributors for this article] (2026). Exploring the genetic landscape of ciprofloxacin-induced DNA supercompaction in Escherichia coli. Nucleic Acids Research (NAR). ISSN 0305-1048. 54(12). doi: 10.1093/nar/gkag573. Full text in Research Archive
• Haldorsen, Bjørg; Augustinussen, Marita Helen; Matuschek, Erika; Småbrekke, Lars; Skjold, Frode & Hegstad, Joachim [Show all 59 contributors for this article] (2026). Performance of EUCAST disc diffusion and supplementary methods to detect reduced susceptibility to linezolid in enterococci— the NordicAST LRE-study. Journal of Antimicrobial Chemotherapy. ISSN 0305-7453. 81(6). doi: 10.1093/jac/dkag174. Full text in Research Archive Show summary

  Objectives This multicentre study aimed to assess performance of the EUCAST disc diffusion (DD) and MIC methods for linezolid susceptibility testing in a genetically diverse strain collection. Methods Nordic clinical microbiology laboratories (n = 83) were invited to test a blinded collection of well-characterized Enterococcus faecalis (n = 10) and Enterococcus faecium (n = 10) strains using the EUCAST DD and gradient tests [Etest and MIC Test strips (MTS)] from two manufacturers (bioMerieux and Liofilchem). Results were compared to reference broth microdilution (BMD) MICs and genotype (presence/absence of linezolid resistance determinants). Results Forty-five laboratories provided DD, and 41 gradient test results. Comparing DD with reference MICs and genotype yielded overall categorical agreements (CA) of 87.0% and 97.8%, respectively. Essential agreement (EA) was 99.7% for Etest (bias +10.0%) and 84.5% for MTS (bias +71.0%). Susceptibility categorization with Etest and MTS showed CA of 90.5% and 84.1% with reference MICs, and 82.9% and 98.6% with genotype, respectively. Most discrepancies involved strains with borderline linezolid MICs (4–8 mg/L) and known linezolid resistance mechanisms. Linezolid exposure of strains with MIC 4 mg/L carrying transferable resistance genes (optrA or poxtA), led to MIC increasing above the clinical breakpoint. Conclusions Etest and EUCAST DD had the highest CAs with linezolid reference MIC. EUCAST DD method and MTS gradient test consistently detected strains with confirmed resistance mechanisms. Our findings highlight the potential clinical implications of resistance determinants in MIC borderline strains and support the need for an area of technical uncertainty or a warning in breakpoint tables for linezolid in enterococci.

• Vaz, Filipa Baltazar da Costa; Lindeman, Ida; Hoffmann, Henriette H.; Skagen, Christine; Steffensen, Anne Katrine & Bjørnholt, Jørgen Vildershøj [Show all 10 contributors for this article] (2026). Distinct systemic and gut IgA responses to bacteria of the human upper gastrointestinal tract. Cell reports. 45(8), p. 1–21. doi: 10.1016/j.celrep.2026.117721. Full text in Research Archive
• Huncikova, Zuzana; Christensen, Martin; Wolden, Runa; Venter, Hermoine Jean; Gammelsrud, Karianne Wiger & Bjørnholt, Jørgen [Show all 15 contributors for this article] (2026). CoNS blood culture isolates from very preterm infants: antibiotic susceptibility, synergy testing and mecA gene expression. JAC-Antimicrobial Resistance (JAC-AMR). 8(2). doi: 10.1093/jacamr/dlag058. Full text in Research Archive Show summary

  Objectives: Previous reports suggest that neonatal sepsis with methicillin-resistant (MR) CoNS can be treated with first-generation cephalosporins. We have evaluated the in vitro effect of cefazolin and other antibiotics, synergy between β-lactams and aminoglycosides, and mecA expression in MR-CoNS isolates. Patients and methods: Antimicrobial susceptibility testing was performed in 167 CoNS isolates from 135 very preterm infants (<32 weeks gestation) with late-onset sepsis. Microbroth dilution chequerboard assay explored antibiotic synergy. PCR detected mecA and three aminoglycoside-modifying enzyme genes. Induction experiments evaluated if exposure to cefazolin induces resistance. RT-PCR determined mecA expression in selected MR-CoNS isolates with different cefazolin/oxacillin MICs. Results: All CoNS isolates were susceptible to amikacin and vancomycin. Most were phenotypically resistant to gentamicin (92%) and cefoxitin (93%), and 89% carried the mecA gene. MIC90 values of cefazolin and oxacillin were 16 mg/L and >256 mg/L, respectively. At the cefazolin breakpoint of 8 mg/L, 83% of isolates were susceptible in vitro. No antibiotic combinations showed synergy using the FIC index, but cefazolin combined with aminoglycosides had favourable susceptibility breakpoint index values. In a simplified synergy screen of ‘highly resistant’ isolates, growth was inhibited with a combination of gentamicin and cefazolin at sub-MIC concentrations in 8/42 (19%) isolates. Exposure to cefazolin sub-MICs caused reduced susceptibility in 1/30 (3%) tested isolates. The highest mecA expression was observed in isolates with high oxacillin/cefazolin MICs. Conclusions: CoNS isolates had lower MICs for cefazolin than oxacillin, and 83% were in vitro susceptible to cefazolin. A clinical trial comparing cefazolin with vancomycin as empirical therapy for suspected neonatal sepsis is warranted.

• Arendrup, Maiken Cavling; Guinea, Jesus; Arikan-Akdagli, Sevtap; Meijer, Eelco F.J.; Meis, Jacques F. & Buil, Jochem B. [Show all 23 contributors for this article] (2025). How to interpret MICs of amphotericin B, echinocandins and flucytosine against Candida auris (Candidozyma auris) according to the newly established European Committee for Antimicrobial Susceptibility Testing (EUCAST) breakpoints. Clinical Microbiology and Infection (CMI). ISSN 1198-743X. 32(1), p. 56–61. doi: 10.1016/j.cmi.2025.07.002. Full text in Research Archive
• Vestad, Beate; Hanzely, Petra; Karaliūtė, Indrė; Ramberg, Oda Helgesen; Skiecevičienė, Jurgita & Lukoševičius, Rokas [Show all 12 contributors for this article] (2025). Modulation of Dextran Sodium Sulfate-Induced Colitis in Germ-Free Mice by Enterococcus faecalis Monocolonization. Microorganisms. 13(12). doi: 10.3390/microorganisms13122864. Full text in Research Archive Show summary

  Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis (UC), are characterized by chronic gastrointestinal inflammation and involve complex interactions of genetic, environmental, and immune factors. Enterococcus faecalis, a gut commensal bacterium, has been implicated in IBD pathogenesis. This study investigated the effects of monocolonization with a UC-derived E. faecalis strain on acute dextran sulfate sodium (DSS)-induced colitis in germ-free (GF) mice, focusing on epithelial injury, inflammatory markers, hematologic indices, and bacterial translocation. In DSS-treated mice, monocolonization was associated with modest and mixed effects, including a higher colitis-related disease activity score, reduced anemia, increased fecal albumin and a trend towards reduced fecal calprotectin. Despite translocation of E. faecalis to mesenteric lymph nodes, no systemic dissemination was observed. Histological analysis revealed broadly similar inflammatory patterns between DSS-treated groups, with slightly more epithelial injury observed in colonized mice. These findings suggest that E. faecalis may influence discrete aspects of DSS injury in a strain-dependent and context-specific manner, rather than broadly altering overall disease severity. This study highlights the utility of GF models for examining strain-specific host–microbe interactions and underscores that individual bacterial isolates may exert heterogeneous and selective effects on acute colitis. Further research is needed to elucidate these complex mechanisms.

• Hanzely, Petra; Holm, Kristian; Bjørnholt, Jørgen Vildershøj; Melum, Espen; Hov, Johannes Espolin Roksund & Rasmussen, Henrik (2025). Efficacy of oral and rectal administration of human faecal microbiota transplant (FMT) in human microbiota-associated mouse models. Scientific Reports. 15(1), p. 1–10. doi: 10.1038/s41598-025-32072-0. Full text in Research Archive Show summary

  The gut microbiome has gained significant interest due to its association with immune dysregulation, allergies, autoimmune conditions, metabolic disorders, and inflammation-associated malignancies. Understanding underlying mechanisms requires appropriate in vivo models, such as human microbiota-associated mouse models to study the microbiota–host interactions. This study compared the efficacy of oral and rectal administration of human faecal microbiota transplant (FMT) from a single donor in C57BL/6J germ-free mice as these methods are often used interchangeably. Using 16S rRNA sequencing, we quantified colonisation efficacy in luminal and tissue samples from orally- (n = 6) and rectally- (n = 6) colonised mice. We detected 84 genera in the FMT sample, 17 of which were not transferred at all, while additional 7 genera were found exclusively in rectally-colonised mice. A significantly higher proportion of amplicon sequence variants (ASVs) (33% vs. 26%; P < 0.05) and genera (32% vs. 25%; P < 0.05) were absent in orally- compared to rectally-colonised group. Some taxa showed different relative abundances in human vs. mouse samples (e.g. Alistipes and Bacteroides relatively more abundant in mice while Faecalibacterium considerably decreased). Beta diversity analysis revealed greater similarity between FMT and tissue samples irrespective of the administration route, with distinct separation of the tissue and luminal samples. Overall, rectal administration yielded more overlapping genera and ASVs with FMT, highlighting that it could have advantages compared with oral administration for microbiota establishment studies

• Danielsen, Anders Skyrud; Johansen, Amalie; Sare, Miriam; Lim, Cherry; Bjørnholt, Jørgen & Furberg, Anne-Sofie [Show all 7 contributors for this article] (2025). Two decades of bacteraemia in Norway: an ecological study of incidence and shifts in microbial epidemiology, 2005–2024. Scientific Reports. 15. doi: 10.1038/s41598-025-28472-x. Full text in Research Archive Show summary

  This study aimed to describe temporal changes in the incidence and microbial composition of bacteraemia in Norway from 2005 to 2024. Using national surveillance data from all microbiology laboratories, combined with contextual indicators such as population size, hospital activity, immunosuppression, and cancer incidence, we conducted an ecological analysis of annual aggregated data. The number of isolates from blood cultures increased from 10,964 in 2005 to 22,679 in 2024, or from 238.0 to 408.6 per 100,000 people, while the estimated blood culture positivity rate remained stable at approximately 6%. Escherichia coli, Staphylococcus aureus, and Klebsiella spp. were the most frequent pathogens in 2024, while the proportion of Streptococcus pneumoniae declined by nearly 40%. The apparent rise in the Gram-negative to Gram-positive ratio was largely explained by this decline in pneumococci. Regression models showed a steady increase in incidence of bacteraemia over time, with minimal impact of age adjustment. Increased diagnostic activity is probably driven by a larger share of inpatients meeting criteria for blood culture, consistent with a frailer and more complex case-mix. The relative stability of estimated positivity rate and the proportion of coagulase-negative staphylococci support that the rise reflects a real increase in the underlying burden of bloodstream infections.

• Danielsen, Anders Skyrud; Lim, Cherry; Yoon, Chang Ho; Gran, Jon Michael; Kacelnik, Oliver & Eyre, David W. [Show all 7 contributors for this article] (2025). Epidemiology and excess mortality of antimicrobial resistance in bacteraemias among cancer patients: A cohort study using routinely collected health data from regional hospital trusts in Oxford and Oslo, 2008-2018. BMJ Open. 15(6). doi: 10.1136/bmjopen-2024-092740. Full text in Research Archive Show summary

  Objectives We investigated the epidemiology and impact on mortality of antimicrobial resistance (AMR) in cancer patients with bacteraemia at Oxford University Hospitals (OxUH), UK, and Oslo University Hospital (OsUH), Norway, during 2008–2018. Design Historical cohort study. Setting Regional hospital trusts with multiple sites in OxUH and OsUH. Methods Patients with cancer and blood cultures positive for one of six pathogen groups during a hospital stay within 3 years following their first cancer diagnosis were followed for 30 days after their first bacteraemia episode. We determined the number of cases and the proportion of infections with an AMR phenotype. Excess mortality and the population-attributable fraction (PAF) due to AMR were estimated by contrasting observed mortality at the end of follow-up with an estimated counterfactual scenario where AMR was absent from all bacteraemias, using inverse probability weighting. Main outcome measure 30-day all-cause mortality following the first bacteraemia episode. Main exposure measure A resistant phenotype of the causative pathogen. Results The study included 1929 patients at OxUH and 1640 patients at OsUH. The highest resistance proportions were found for vancomycin resistance in enterococci (85/314, 27.1%) and carbapenem-resistance in Pseudomonas aeruginosa (63/260, 24.2%) at OxUH, and third-generation cephalosporin resistance in Escherichia coli (62/743, 8.3%) and Klebsiella pneumoniae (14/223, 6.3%) at OsUH. Observed mortality for all infections was 26.4% at OxUH, with an estimated counterfactual mortality without AMR of 24.7%, yielding an excess mortality of 1.7% (95% CI: 0.8 to 2.5%). The PAF was 6.3% (95% CI: 2.9 to 9.6%), meaning an estimated 32 of 509 deaths could be attributed to AMR. Limited events at OsUH precluded a similar estimate. Conclusions Despite estimating modest excess mortality, the mortality attributable to resistance in these two high-income, low-prevalence settings highlights the potential for escalation if global resistance trends continue to worsen.

• Danielsen, Anders Skyrud; Nygaard, Nina Johanne; Børseth, Anita Wang; Nilsen, Jorunn V.; Øvreness, H. & Raastad, Ragnhild [Show all 9 contributors for this article] (2024). Patient perspectives on infection prevention and control in cancer care: a survey of knowledge and attitudes among persons with cancer and their next of kin. Journal of Hospital Infection. ISSN 0195-6701. 146, p. 21–30. doi: 10.1016/j.jhin.2024.01.012. Full text in Research Archive Show summary

  Background: With the growing prevalence of antimicrobial resistance, there may be a need to strengthen infection prevention and control (IPC) measures in cancer care. When developing clinical guidelines, it is important to incorporate patient perspectives. Aim: To determine the knowledge of, and attitudes towards, IPC among persons with cancer and their next of kin in Norway. Methods: Through discussions in expert panels and a pilot study, a survey was developed consisting of 13 knowledge statements to be judged true/false and 40 attitude items to be judged using a Likert scale and was sent to a panel of people with cancer experience on August 22nd, 2023. The mean correct responses and attitude scores were reported. Findings: Of 551 respondents, the mean correct response to IPC-related knowledge questions was 79% (95% confidence interval: 78–80). Respondents were most knowledgeable about hand hygiene (99%, 546/551), but least knowledgeable about its role in preventing antibiotic resistance (41%, 225/551). Strong support was noted for IPC, especially within the patient responsibilities theme, with a mean score of 4.83. However, there was a notable reluctance towards some selected intrusive IPC measures, such as reducing contact with close relations. Conclusion: This survey revealed a high level of knowledge and attitudes that support the importance of IPC among persons with cancer in Norway and their next of kin. We recommend including patient perspectives in future development of IPC guidelines.

• Fostervold, Aasmund; Raffelsberger, Niclas Peter; Hetland, Marit; Bakksjø, Ragna-Johanne; Bernhoff, Eva & Samuelsen, Ørjan [Show all 22 contributors for this article] (2024). Risk of death in Klebsiella pneumoniae bloodstream infections is associated with specific phylogenetic lineages. Journal of Infection. ISSN 0163-4453. 88(5), p. 1–11. doi: 10.1016/j.jinf.2024.106155. Full text in Research Archive Show summary

  Background: Klebsiella pneumoniae species complex (KpSC) bloodstream infections (BSIs) are associated with considerable morbidity and mortality, particularly in elderly and multimorbid patients. Multidrug-resistant (MDR) strains have been associated with poorer outcome. However, the clinical impact of KpSC phylogenetic lineages on BSI outcome is unclear. Methods: In an 18-month nationwide Norwegian prospective study of KpSC BSI episodes in adults, we used whole-genome sequencing to describe the molecular epidemiology of KpSC, and multivariable Cox regression analysis including clinical data to determine adjusted hazard ratios (aHR) for death associated with specific genomic lineages. Findings: We included 1078 BSI episodes and 1082 bacterial isolates from 1055 patients. The overall 30-day case-fatality rate (CFR) was 12.5%. Median patient age was 73.4, 61.7% of patients were male. Median Charlson comorbidity score was 3. Klebsiella pneumoniae sensu stricto (Kp) (79.3%, n = 858/1082) and K. variicola (15.7%, n = 170/1082) were the dominating phylogroups. Global MDR-associated Kp clonal groups (CGs) were prevalent (25.0%, n = 270/1082) but 78.9% (n = 213/270) were not MDR, and 53.7% (n = 145/270) were community acquired. The major findings were increased risk for death within 30 days in monomicrobial BSIs caused by K. variicola (CFR 16.9%, n = 21; aHR 1.86, CI 1.10-3.17, p = 0.02), and global MDR-associated Kp CGs (CFR 17.0%, n = 36; aHR 1.52, CI 0.98-2.38, p = 0.06) compared to Kp CGs not associated with MDR (CFR 10.1%, n = 46). Conclusion: Bacterial traits, beyond antimicrobial resistance, have a major impact on the clinical outcome of KpSC BSIs. The global spread of MDR-associated Kp CGs is driven by other mechanisms than antibiotic selection alone. Further insights into virulence determinants, and their association with phylogenetic lineages are needed to better understand the epidemiology of KpSC infection and clinical outcome.

• Oldereid, Tine Simensen; Jiang, Xiaojun; Øgaard, Jonas Daniel Sjøberg; Schrumpf, Elisabeth; Bjørnholt, Jørgen & Rasmussen, Henrik [Show all 7 contributors for this article] (2023). Microbial exposure during early life regulates development of bile duct inflammation. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 59(2), p. 192–201. doi: 10.1080/00365521.2023.2278423. Full text in Research Archive Show summary

  Objectives The early life microbiome has been linked to inflammatory diseases in adulthood and a role for the microbiome in bile duct inflammation is supported by both human and murine studies. We utilized the NOD.c3c4 mouse model that develops a spontaneous immune-driven biliary disease with a known contribution of the microbiome to evaluate the temporal effects of the early life microbiome. Materials and methods Germ-free (GF) NOD.c3c4 mice were conventionalized into a specific pathogen free environment at birth (conventionally raised, CONV-R) or at weaning (germ-free raised, GF-R) and compared with age and gender-matched GF and conventional (CONV) NOD.c3c4 mice. At 9 weeks of age, liver pathology was assessed by conventional histology and flow cytometry immunophenotyping. Results Neonatal exposure to microbes (CONV-R) increased biliary inflammation to similar levels as regular conventional NOD.c3c4 mice, while delayed exposure to microbes (GF-R) restrained the biliary inflammation. Neutrophil infiltration was increased in all conventionalized mice compared to GF. An immunophenotype in the liver similar to CONV was restored in both CONV-R and GF-R compared to GF mice displaying a proportional increase of B cells and reduction of T cells in the liver. Conclusions Microbial exposure during early life has a temporal impact on biliary tract inflammation in the NOD.c3c4 mouse model suggesting that age-sensitive interaction with commensal microbes have long-lasting effects on biliary immunity that can be of importance for human cholangiopathies.

• Oldereid, Tine Simensen; Jiang, Xiaojun; Nordhus, Kathrine Sivertsen; Ponzetta, Andrea; Bjørnholt, Jørgen & Björkström, Niklas K. [Show all 8 contributors for this article] (2023). Role of bacteria and microbial metabolites in immune modulation during early life. Scandinavian Journal of Immunology. ISSN 0300-9475. doi: 10.1111/sji.13336. Full text in Research Archive Show summary

  Abstract Host–microbiome interplay from birth is essential for immune imprinting and tuning. Live gut microbes and microbial‐derived metabolites regulate the development and modulation of the immune system, but whether microbial metabolites solely are sufficient to induce immune maturation remains unclear. Sterile faecal filtrates (FFT) were generated from murine gut contents. Newborn germ‐free (GF) mice were treated twice daily with FFT (GF‐FFT) or saline (GF‐NaCl) from post‐natal day 5 until 4 weeks of age. A third group of GF neonates were conventionalized by the transfer of caecal microbiota with live gut microbes. Host immune compartments were comprehensively immunophenotyped and systemically analysed in all available immune‐related organs using flow cytometry. Oral FFT was associated with reduced survival among neonates (n = 7/19; 36.8% mortality), while saline treatment was well tolerated (n = 1/17, 5.9% mortality). Four‐week‐old FFT‐treated pups were comparable in body weight to GF‐NaCl, and the major B‐cell, conventional T‐cell and unconventional T‐cell subsets were unchanged from saline‐treated mice. Live bacteria administered during early life induced clear changes in proportions of B cells, T cells and T‐cell subsets in all mucosal tissues and secondary lymphoid organs compared to GF‐FFT, including restoration of intestinal natural killer T (NKT) cells with characteristics similar to conventional pups. Our findings show that oral administration of a FFT made of microbial metabolites, antigens and bacteriophages alone is insufficient to induce normal immune development elicited by the presence of live bacteria. Reduced survival during neonatal FFT treatment suggests a potential bioactive attribute of sterile faecal filtrates.

• Hegstad, Kristin; Pöntinen, Anna Kaarina; Bjørnholt, Jørgen; Paulsen, Else Quist & Sundsfjord, Arnfinn Ståle (2023). The first tigecycline resistant Enterococcus faecium in Norway was related to tigecycline exposure. Journal of Global Antimicrobial Resistance. ISSN 2213-7165. 36, p. 112–115. doi: 10.1016/j.jgar.2023.12.002. Full text in Research Archive Show summary

  Objectives - We describe the first tigecycline resistant enterococcal isolate in Norway and the mechanisms involved.<p> <p>Material and methods - The Norwegian National Advisory Unit on Detection of Antimicrobial Resistance (K-res). received in 2022 an Enterococcus faecium blood culture isolate with decreased susceptibility to tigecycline from a hospitalized patient in the South-Eastern Norway Health region for confirmatory testing. K-res verified a tigecycline-resistant E. faecium (TigR) with broth microdilution MIC of 0.5 mg/L. The patient had received treatment with tigecycline because of an infection with a linezolid- and vancomycin-resistant but tigecycline susceptible E. faecium (TigS) 47 days prior to the detection of the corresponding tigecycline-resistant isolate. Whole-genome comparisons, cgMLST and SNP analyses revealed that the two ST117 strains were closely related.<p> <p>Results - The TigR isolate showed a novel deletion of 2 amino acids (K57Y58) in a polymorphic region of ribosomal protein S10 previously associated with tigecycline resistance and a deletion of the tet(M) leader peptide previously related to increased expression of tet(M) and tigecycline resistance in enterococci.<p> <p>Conclusions - Genomic and epidemiological analyses confirm that the two E. faecium (TigR and TigS) are closely related isolates of the same strain and that the two deletions (in rpsJ and of tet(M) leader peptide) account for the tigecycline resistance in TigR.

• Rubaye, Mushtaq al; Janice, Jessin; Bjørnholt, Jørgen Vildershøj; Kacelnik, Oliver; Haldorsen, Bjørg C. & Nygaard, Randi M. [Show all 26 contributors for this article] (2023). The population structure of vancomycin-resistant and -susceptible Enterococcus faecium in a low-prevalence antimicrobial resistance setting is highly influenced by circulating global hospital-associated clones. Microbial Genomics. 9(12). doi: 10.1099/mgen.0.001160. Full text in Research Archive Show summary

  Between 2010 and 2015 the incidence of vancomycin-resistant Enterococcus faecium (VREfm) in Norway increased dramatically. Hence, we selected (1) a random subset of vancomycin-resistant enterococci (VRE) from the Norwegian Surveillance System for Communicable Diseases (2010–15; n=239) and (2) Norwegian vancomycin-susceptible E. faecium (VSEfm) bacteraemia isolates from the national surveillance system for antimicrobial resistance in microbes (2008 and 2014; n=261) for further analysis. Whole-genome sequences were collected for population structure, van gene cluster, mobile genetic element and virulome analysis, as well as antimicrobial susceptibility testing. Comparative genomic and phylogeographical analyses were performed with complete genomes of global E. faecium strains from the National Center for Biotechnology Information (NCBI) (1946–2022; n=272). All Norwegian VREfm and most of the VSEfm clustered with global hospital-associated sequence types (STs) in the phylogenetic subclade A1. The vanB2 subtype carried by chromosomal Tn1549 integrative conjugative elements was the dominant van type. The major Norwegian VREfm cluster types (CTs) were in accordance with concurrent European CTs. The dominant vanB-type VREfm CTs, ST192-CT3/26 and ST117-CT24, were mostly linked to a single hospital in Norway where the clones spread after independent chromosomal acquisition of Tn1549. The less prevalent vanA VRE were associated with more diverse CTs and vanA carrying Inc18 or RepA_N plasmids with toxin–antitoxin systems. Only 5 % of the Norwegian VRE were Enterococcus faecalis, all of which contained vanB. The Norwegian VREfm and VSEfm isolates harboured CT-specific virulence factor (VF) profiles supporting biofilm formation and colonization. The dominant VREfm CTs in general hosted more virulence determinants than VSEfm. The phylogenetic clade B VSEfm isolates (n=21), recently classified as Enterococcus lactis, harboured fewer VFs than E. faecium in general, and particularly subclade A1 isolates. In conclusion, the population structure of Norwegian E. faecium isolates mirrors the globally prevalent clones and particularly concurrent European VREfm/VSEfm CTs. Novel chromosomal acquisition of vanB2 on Tn1549 from the gut microbiota, however, formed a single major hospital VREfm outbreak. Dominant VREfm CTs contained more VFs than VSEfm.

• Rubaye, Mushtaq Talib Shawi al; Janice, Jessin; Bjørnholt, Jørgen; Löhr, Iren Høyland; Sundsfjord, Arnfinn Ståle & Hegstad, Kristin (2023). The first vanE-type vancomycin resistant Enterococcus faecalis isolates in Norway – phenotypic and molecular characteristics. Journal of Global Antimicrobial Resistance. ISSN 2213-7165. 36, p. 193–199. doi: 10.1016/j.jgar.2023.12.021. Full text in Research Archive Show summary

  Objectives We aimed to characterize the vanE cluster and its genetic support in the first Norwegian vanE-type isolates and assess genetic relatedness to other vanE isolates. Methods Two vanE-type vancomycin resistant Enterococcus faecalis (vanE-VREfs) isolates (E1 and E2) recovered from the same patient 30 months apart were examined for antimicrobial susceptibility, genome sequence, vancomycin resistance induction, vanE transferability, genome mutation rate, and phylogenetic relationship to E. faecalis closed genomes and two vanE-VREfs from North America. Results The ST34 E1 and E2 strains expressed low-level vancomycin resistance and susceptibility to teicoplanin. Their vanE gene clusters were part of a non-transferable Tn6202. The histidine kinase part of vanSE was expressed although a premature stop codon (E1) and insertion of a transposase (E2) truncated their vanSE gene. The vancomycin resistance phenotype in E1 was inducible while constitutive in E2. E1 showed a 125-fold higher mutation rate than E2. Variant calling showed 60 variants but nearly identical chromosomal gene content and synteny between the isolates. Their genomes also showed high similarity to another ST34 vanE-VREfs from Canada. Conclusion In-depth genomic analyses of the first two vanE-VREfs found in Europe identified a single chromosomal insertion site of two variants of vanE-conferring Tn6202. Single nucleotide polymorphism (SNP) and core genome multilocus sequence type (cgMLST) analyses show the genomes are different. This can be explained by the high mutation rate of E1 and acquisition of different mobile genetic elements; thus, we believe the two isolates from the same patient are genetically related. Genome similarities also suggest relatedness between the Canadian and Norwegian vanE-VREfs.

• Corwin, Linn Merete B.; Ingebretsen, André; Campbell, Patricia; Alfsnes, Kristian; Müller, Fredrik & Mauder, Norman [Show all 8 contributors for this article] (2023). Fourier transform infrared spectroscopy; can it be used as a rapid typing method of Neisseria gonorrhoeae? Journal of Microbiological Methods. ISSN 0167-7012. 205, p. 1–9. doi: 10.1016/j.mimet.2023.106675. Full text in Research Archive Show summary

  Background Typing of Neisseria gonorrhoeae is necessary for epidemiologic surveillance, while time consuming and resource intensive. Fourier transform infrared (FTIR) spectroscopy has shown promising results when typing several bacterial species. This study investigates whether FTIR spectroscopy can be used as a rapid method for typing clinical N. gonorrhoeae isolates, comparing FTIR spectroscopy to multi locus sequence typing (MLST), N. gonorrhoeae multi antigen sequence typing (NG-MAST) and whole genome sequencing (WGS). Methods Sixty consecutive isolates from a venereology clinic and three isolates from an outbreak were included. Isolates were analysed with FTIR spectroscopy on the IR Biotyper system (Bruker Daltonik) with the IR Biotyper software (version 2.1) with default analysis settings (spectral range 1300–800 cm−1). Four technical replicates of each isolate were analysed in three different runs. The output was a hierarchical cluster analysis (HCA) presented as a dendrogram; a tree-like overview of how closely different isolates are related. FTIR spectroscopy was compared to MLST, NG-MAST and WGS to see if the FTIR spectroscopy-dendrogram grouped the isolates in the same clusters. Results Fifty-one out of 60 isolates, and the three outbreak isolates, produced at least one spectrum in each run and were included. No agreement between FTIR spectroscopy and MLST or NG-MAST or WGS was shown. The FTIR spectroscopy-dendrogram failed to cluster the outbreak isolates. Conclusion FTIR spectroscopy (spectral range 1300–800 cm−1) is not yet suitable for epidemiologic typing of N. gonorrhoeae. Absence of a capsule as well as phase- and antigenic variation of carbohydrate surface structures of the gonococcal cell wall may contribute to our findings. Future studies should include analysis of a wider range of the spectrum recorded (4000-500 cm−1), and should also explore further mathematical analytic approaches of the similarity between spectra.

• Heim, Amalie Von Barner Tvedegaard; Janice, Jessin; Bjørnholt, Jørgen; Lunestad, Bjørn Tore; Hegstad, Kristin & Svanevik, Cecilie Smith (2023). Genomic insights into Enterococcus faecium isolates from marine bivalves highlight One Health concerns and healthcare linkages. Microbial Genomics. 9(12), p. 1–15. doi: 10.1099/mgen.0.001154. Full text in Research Archive Show summary

  Enterococci, especially Enterococcus faecium, are one of today’s leading causes of multidrug-resistant infections in hospital settings. The marine environment may harbour enterococci, but its role as an evolutionary niche and as a vector for the spread of enterococci is sparsely investigated. Hence, by applying enterococci in bivalves as a sentinel tool, this study aimed to describe the prevalence of enterocooci along the Norwegian coast and in addition the phylogeny of E. faecium in particular. Enterococci in batch samples of marine bivalves, harvested from 86 different locations, were quantitatively examined by a culture-dependent most probable number (MPN) method. Isolates were identified by MALDI-TOF-MS prior to antimicrobial susceptibility testing by broth microdilution. In-detail analyses of a representative selection of E. faecium isolates (n=148) were done by Illumina whole-genome sequencing, and assembled genomes were compared to closed E. faecium genomes in the public databases and to genomes from commensal and clinical isolates from Norway. Diversity among E. faecium within the same batch sample of bivalves was also explored. Enterococci were detected in 287 of the 471 examined bivalve samples, but in low concentrations with a median value of <18 MPN /100 g. From positive samples, 479 isolates of enterococci were identified belonging to ten different species, where E. faecium (n=247), Enterococcus hirae (n=114) and Enterococcus faecalis (n=66) were most frequently found. Resistance towards one or more antimicrobial agents was observed in 197 isolates (41 %), none of the isolates showed acquired resistance to vancomycin or linezolid. Phylogenetic analyses revealed high diversity among the E. faecium isolates and showed that the marine niche is dominated by strains from the non-clinical setting belonging to clade A2 (n=85) and B (E. lactis) (n=60). Only three isolates belonged to the hospital-associated clade A1 (ST80 and ST117). Two of these clustered with one isolate from a hospitalized patient and one from a non-hospitalized person. This study demonstrated a high prevalence, but low concentrations of enterococci in bivalves, and low levels of antimicrobial resistance. E. faecium genomes showed high population diversity and that very few E. faecium isolates in bivalves may have arisen from the human healthcare system. A systematic surveillance of target micro-organisms applying methods examining multiple isolates from the same bivalve sample provides important data to assess the enterococcal phylogeny, antimicrobial resistance and the level of faecal pollution in the marine environment.

• Danielsen, Anders Skyrud; Elstrøm, Petter; Eriksen-Volle, Hanne-Merete; Hofvind, Solveig Sand-Hanssen; Eyre, David W. & Kacelnik, Oliver [Show all 7 contributors for this article] (2023). The epidemiology of multidrug-resistant organisms in persons diagnosed with cancer in Norway, 2008–2018: expanding surveillance using existing laboratory and register data. European Journal of Clinical Microbiology and Infectious Diseases. ISSN 0934-9723. 43, p. 121–132. doi: 10.1007/s10096-023-04698-3. Full text in Research Archive Show summary

  Abstract Surveillance has revealed an increase of multidrug-resistant organisms (MDROs), even in low-prevalent settings such as Norway. MDROs pose a particular threat to at-risk populations, including persons with cancer. It is necessary to include such populations in future infection surveillance. By combining existing data sources, we aimed to describe the epidemiology of MDROs in persons diagnosed with cancer in Norway from 2008 to 2018. A cohort was established using data from the Cancer Registry of Norway, which was then linked to notifications of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin- and/or linezolid-resistant enterococci (V/LRE), and carbapenemase-producing Gram-negative bacilli (CP-GNB) from the Norwegian Surveillance System for Communicable Diseases, and laboratory data on third-generation cephalosporin-resistant Enterobacterales (3GCR-E) from Oslo University Hospital (OUH). We described the incidence of MDROs and resistance proportion in Enterobacterales from 6 months prior to the person’s first cancer diagnosis and up to 3 years after. The cohort included 322,005 persons, of which 0.3% (878) were diagnosed with notifiable MDROs. Peak incidence rates per 100,000 person-years were 60.9 for MRSA, 97.2 for V/LRE, and 6.8 for CP-GNB. The proportion of 3GCR-E in Enterobacterales in blood or urine cultures at OUH was 6% (746/12,534). Despite overall low MDRO incidence, there was an unfavourable trend in the incidence and resistance proportion of Gram-negative bacteria. To address this, there is a need for effective infection control and surveillance. Our study demonstrated the feasibility of expanding the surveillance of MDROs and at-risk populations through the linkage of existing laboratory and register data.

• Ljungquist, Oskar; Haldorsen, Bjørg; Pöntinen, Anna Kaarina; Janice, Jessin; Josefsen, Ellen Haldis & Elstrøm, Petter [Show all 28 contributors for this article] (2023). Nationwide, population-based observational study of the molecular epidemiology and temporal trend of carbapenemase-producing Enterobacterales in Norway, 2015 to 2021. Eurosurveillance. ISSN 1025-496X. 28(27), p. 1–11. doi: 10.2807/1560-7917.es.2023.28.27.2200774. Full text in Research Archive Show summary

  Introduction National and regional carbapenemase-producing Enterobacterales (CPE) surveillance is essential to understand the burden of antimicrobial resistance, elucidate outbreaks, and develop infection-control or antimicrobial-treatment recommendations. Aim This study aimed to describe CPE and their epidemiology in Norway from 2015 to 2021. Methods A nationwide, population-based observational study of all verified clinical and carriage CPE isolates submitted to the national reference laboratory was conducted. Isolates were characterised by antimicrobial susceptibility testing, whole genome sequencing (WGS) and basic metadata. Annual CPE incidences were also estimated. Results A total of 389 CPE isolates were identified from 332 patients of 63 years median age (range: 0-98). These corresponded to 341 cases, 184 (54%) being male. Between 2015 and 2021, the annual incidence of CPE cases increased from 0.6 to 1.1 per 100,000 person-years. For CPE-isolates with available data on colonisation/infection, 58% (226/389) were associated with colonisation and 38% (149/389) with clinical infections. WGS revealed a predominance of OXA-48-like (51%; 198/389) and NDM (34%; 134/389) carbapenemases in a diversified population of Escherichia coli and Klebsiella pneumoniae, including high-risk clones also detected globally. Most CPE isolates were travel-related (63%; 245/389). Although local outbreaks and healthcare-associated transmission occurred, no interregional spread was detected. Nevertheless, 18% (70/389) of isolates not directly related to import points towards potentially unidentified transmission routes. A decline in travel-associated cases was observed during the COVID-19 pandemic. Conclusions The close-to-doubling of CPE case incidence between 2015 and 2021 was associated with foreign travel and genomic diversity. To limit further transmission and outbreaks, continued screening and monitoring is essential.

• Corwin, Linn Merete B.; Campbell, Patricia; Jakobsen, Kirsti; Müller, Fredrik; Lai, Xiaoran & Unemo, M. [Show all 9 contributors for this article] (2023). Improvement in Neisseria gonorrhoeae culture rates by bedside inoculation and incubation at a clinic for sexually transmitted infections. Annals of Clinical Microbiology and Antimicrobials. 22. doi: 10.1186/s12941-023-00576-0. Full text in Research Archive Show summary

  Background Culture of Neisseria gonorrhoeae is essential for surveillance of complete antimicrobial susceptibility profiles. In 2014, the culture success rate of N. gonorrhoeae from samples taken at the clinic for sexually transmitted infections (STI clinic), Oslo University Hospital, Norway, was only 20%. The present study aimed to improve gonococcal culture rates using bedside inoculation of patient samples on gonococcal agar plates and incubation at the STI clinic. Methods This prospective quality improvement study was conducted by the STI clinic and the Department of Microbiology at Oslo University Hospital from May 2016 - October 2017. When culture of N. gonorrhoeae was clinically indicated, we introduced a parallel ‘bedside culture’ at the STI clinic and compared results with the standard culture at the microbiology department. Samples were taken from urethra, anorectum, pharynx and cervix. Culture rates were compared across symptomatic and asymptomatic anatomical sites. Results From 596 gonococcal-positive PCR samples, bedside culture had a significantly higher success rate of 57% compared to 41% with standard culture (p < 0.05). Overall, culture rate from symptomatic sites was 91% v. 45% from asymptomatic sites. The culture rates from different anatomical sites were as follows: urethra 93%, anorectum 64%, pharynx 28% and cervix 70%. Bedside culture significantly (p < 0.05) improved the culture rates for symptomatic urethral and asymptomatic pharyngeal samples. Conclusions Where feasible, bedside inoculation on gonococcal agar plates and incubation of samples from patients with gonorrhoea is recommended. This will improve the culture diagnostics and provide additional gonococcal isolates for antimicrobial resistance surveillance.

• Christensen, Ingrid; Berild, Dag; Bjørnholt, Jørgen; Jelsness-Jørgensen, Lars-Petter; Debes, Sara Molvig & Haug, Jon Birger (2023). The Role of Procalcitonin as an Antimicrobial Stewardship Tool in Patients Hospitalized with Seasonal Influenza. Antibiotics. 12(3). doi: 10.3390/antibiotics12030573. Full text in Research Archive Show summary

  Background: Up to 60% of the antibiotics prescribed to patients hospitalized with seasonal influenza are unnecessary. Procalcitonin (PCT) has the potential as an antimicrobial stewardship program (ASP) tool because it can differentiate between viral and bacterial etiology. We aimed to explore the role of PCT as an ASP tool in hospitalized seasonal influenza patients. Methods: We prospectively included 116 adults with seasonal influenza from two influenza seasons, 2018–2020. All data was obtained from a single clinical setting and analyzed by descriptive statistics and regression models. Results: In regression analyses, we found a positive association of PCT with 30 days mortality and the amount of antibiotics used. Influenza diagnosis was associated with less antibiotic use if the PCT value was low. Patients with a low initial PCT (<0.25 µg/L) had fewer hospital and intensive care unit (ICU) days and fewer positive chest X-rays. PCT had a negative predictive value of 94% for ICU care stay, 98% for 30 days mortality, and 88% for bacterial coinfection. Conclusion: PCT can be a safe rule-out test for bacterial coinfection. Routine PCT use in seasonal influenza patients with an uncertain clinical picture, and rapid influenza PCR testing, may be efficient as ASP tools.

• Danielsen, Anders Skyrud; Franconeri, Léa; Page, Samantha; Myhre, Anders Eivind; Tornes, Ragnhild Agathe & Kacelnik, Oliver [Show all 7 contributors for this article] (2023). Clinical outcomes of antimicrobial resistance in cancer patients: a systematic review of multivariable models. BMC Infectious Diseases. 23(1). doi: 10.1186/s12879-023-08182-3. Full text in Research Archive Show summary

  Background Infections are major causes of disease in cancer patients and pose a major obstacle to the success of cancer care. The global rise of antimicrobial resistance threatens to make these obstacles even greater and hinder continuing progress in cancer care. To prevent and handle such infections, better models of clinical outcomes building on current knowledge are needed. This internally funded systematic review (PROSPERO registration: CRD42021282769) aimed to review multivariable models of resistant infections/colonisations and corresponding mortality, what risk factors have been investigated, and with what methodological approaches. Methods We employed two broad searches of antimicrobial resistance in cancer patients, using terms associated with antimicrobial resistance, in MEDLINE and Embase through Ovid, in addition to Cinahl through EBSCOhost and Web of Science Core Collection. Primary, observational studies in English from January 2015 to November 2021 on human cancer patients that explicitly modelled infection/colonisation or mortality associated with antimicrobial resistance in a multivariable model were included. We extracted data on the study populations and their malignancies, risk factors, microbial aetiology, and methods for variable selection, and assessed the risk of bias using the NHLBI Study Quality Assessment Tools. Results Two searches yielded a total of 27,151 unique records, of which 144 studies were included after screening and reading. Of the outcomes studied, mortality was the most common (68/144, 47%). Forty-five per cent (65/144) of the studies focused on haemato-oncological patients, and 27% (39/144) studied several bacteria or fungi. Studies included a median of 200 patients and 46 events. One-hundred-and-three (72%) studies used a p-value-based variable selection. Studies included a median of seven variables in the final (and largest) model, which yielded a median of 7 events per variable. An in-depth example of vancomycin-resistant enterococci was reported. Conclusions We found the current research to be heterogeneous in the approaches to studying this topic. Methodological choices resulting in very diverse models made it difficult or even impossible to draw statistical inferences and summarise what risk factors were of clinical relevance. The development and adherence to more standardised protocols that build on existing literature are urgent.

• Berild, Dag; Jelsness-Jørgensen, Lars-Petter; Bjørnholt, Jørgen & Haug, Jon Birger (2022). Skreddersydde tiltak gir bedre antibiotikastyring i norske sykehus. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 142(5), p. 1–3. doi: 10.4045/tidsskr.22.0094. Full text in Research Archive
• Christensen, Ingrid; Haug, Jon Birger; Berild, Dag; Bjørnholt, Jørgen; Skodvin, Brita & Jelsness-Jørgensen, Lars-Petter (2022). Factors Affecting Antibiotic Prescription among Hospital Physicians in a Low-Antimicrobial-Resistance Country: A Qualitative Study. Antibiotics. 11(1). doi: 10.3390/antibiotics11010098. Full text in Research Archive Show summary

  Antimicrobial resistance (AMR) is a threat to hospital patients. Antimicrobial stewardship programs (ASPs) can counteract AMR. To optimize ASPs, we need to understand what affects physicians’ antibiotic prescription from several contexts. In this study, we aimed to explore the factors affecting hospital physicians’ antibiotic choices in a low-resistance country to identify potential targets for future ASPs. We interviewed 14 physicians involved in antibiotic prescription in a Norwegian hospital. The interviews were audiotaped, transcribed verbatim, and analyzed using thematic analysis. The main factors affecting antibiotic prescription were a high work pressure, insufficient staff resources, and uncertainties regarding clinical decisions. Treatment expectations from patients and next of kin, benevolence towards the patients, suboptimal microbiological testing, and limited time for infectious disease specialists to offer advisory services also affected the antibiotic choices. Future ASP efforts should evaluate the system organization and prioritizations to address and manage potential time-pressure issues. To limit the use of broad-spectrum antibiotics, improving microbiology testing and the routines for consultations with infectious disease specialists seems beneficial. We also identified a need among the prescribing physicians for a debate on ethical antibiotic questions.

• Al-Rubaye, Mushtaq T.S.; Janice, Jessin; Bjørnholt, Jørgen Vildershøj; Jakovljev, Aleksandra; Hultström, Maria Elisabeth & Sundsfjord, Arnfinn [Show all 7 contributors for this article] (2021). Novel genomic islands and a new vanD-subtype in the first sporadic VanD-type vancomycin resistant enterococci in Norway. PLOS ONE. 16(7). doi: 10.1371/journal.pone.0255187. Full text in Research Archive Show summary

  Background - Vancomycin-resistant enterococci (VRE) represent several types of transferable vancomycin resistance gene clusters. The vanD type, associated with moderate to high level vancomycin resistance, has only sporadically been described in clinical isolates. The aim of this study was to perform a genetic characterization of the first VanD-type VRE strains detected in Norway. Methods - The VanD-type VRE-strains (n = 6) from two patient cases were examined by antimicrobial susceptibility testing and whole genome sequencing (WGS) to uncover Van-phenotype, strain phylogeny, the vanD gene clusters, and their genetic surroundings. The putative transferability of vanD was examined by circularization PCR and filter mating. Results - The VanD-type Enterococcus faecium (n = 4) and Enterococcus casseliflavus (n = 2) strains recovered from two cases (A and B), expressed moderate to high level vancomycin resistance (MIC 64—>256 mg/L) and various levels of teicoplanin susceptibility (MIC 2—>256 mg/L). WGS analyses revealed phylogenetically different E. faecium strains (A1, A2, and A3 of case A and B1 from case B) as well as vanD gene clusters located on different novel genomic islands (GIs). The E. casseliflavus strains (B2 and B3 of case B) were not clonally related, but harbored nearly identical novel GIs. The vanD cluster of case B strains represents a novel vanD-subtype. All the vanD-GIs were integrated at the same chromosomal site and contained genes consistent with a Clostridiales origin. Circular forms of the vanD-GIs were detected in all strains except B1. Transfer of vanD to an E. faecium recipient was unsuccessful. Conclusions - We describe the first VanD-type E. casseliflavus strains, a novel vanD-subtype, and three novel vanD-GIs with a genetic content consistent with a Clostridiales order origin. Despite temporal occurrence, case A and B E. faecium strains were phylogenetically diverse and harbored different vanD subtypes and vanD-GIs.

• Størdal, Eline Hasselgård; Solevåg, Anne Lee; Bjørnholt, Jørgen; Rønnestad, Arild Erland & Stensvold, Hans Jørgen (2021). Sepsis treatment options identified by 10-year study of microbial isolates and antibiotic susceptibility in a level-four neonatal intensive care unit. Acta Paediatrica. ISSN 0803-5253. doi: 10.1111/apa.16189. Full text in Research Archive Show summary

  Aim: This observational study investigated the microbiology of blood culture-positive sepsis episodes and susceptibility to empiric antibiotics in early-onset sepsis (EOS) and late-onset sepsis (LOS) in a level-four neonatal intensive care unit (NICU) from 2010 to 2019. Methods: It was based on patient records and data that Oslo University Hospital, Norway, routinely submitted to the Norwegian Neonatal Network database. Clinical data were merged with blood culture results, including antibiotic susceptibility. Results: We studied 5249 infants admitted to the NICU 6321 times and identified 324 positive blood cultures from 287 infants, with 30 EOS and 305 LOS episodes. Frequent causative agents for EOS were group B streptococci (33.3%), Escherichia coli (20.0%) and Staphylococcus aureus (16.7%). All were susceptible to empiric ampicillin and gentamicin. LOS was most frequently caused by coagulase-negative staphylococci (CONS) (73.8%), Staphylococcus aureus (15.7%) and Enterococci (6.9%). CONS, Staphylococcus aureus, Enterococci, Escherichia coli, Klebsiella and Enterobacter represented 91.9% of LOS episodes and were susceptible to vancomycin and cefotaxime (96.1%), vancomycin and gentamicin (97.0%) and cloxacillin and gentamicin (38.1%). Conclusion: Empiric treatment with ampicillin and gentamicin was adequate for EOS. Combining vancomycin and gentamicin may be a safer alternative to cefotaxime for LOS, as this reduces exposure to broad-spectrum antibiotics.

• Ramstad, Silje; Wasteson, Yngvild; Lindstedt, Bjørn-Arne; Taxt, Arne Michael; Bjørnholt, Jørgen & Brandal, Lin Cathrine T. [Show all 7 contributors for this article] (2021). Characterization of Shiga toxin 2a encoding bacteriophages isolated from high-virulent O145:H25 Shiga toxin-producing Escherichia coli. Frontiers in Microbiology. 12. doi: 10.3389/fmicb.2021.728116. Full text in Research Archive Show summary

  Shiga toxin-producing Escherichia coli (STEC) may cause severe disease mainly due to the ability to produce Shiga toxins (Stx) encoded on bacteriophages. In Norway, more than 30% of the reported cases with STEC O145:H25 develop hemolytic uremic syndrome (HUS), and most cases, with known travel history, acquired the infection domestically. To describe phage characteristics associated with high virulence, we extracted the Stx2a phage sequences from eight clinical Norwegian O145:H25 STEC to conduct in-depth molecular characterization using long and short read sequencing. The Stx2a phages were annotated, characterized, and compared with previously published Stx2a phages isolated from STEC of different serotypes. The Norwegian O145:H25 Stx2a phages showed high sequence identity (&amp;gt;99%) with 100% coverage. The Stx2a phages were located at the integration site yciD , were approximately 45 kbp long, and harbored several virulence-associated genes, in addition to stx2a , such as nanS and nleC . We observed high sequence identity (&amp;gt;98%) and coverage (≥94%) between Norwegian O145:H25 Stx2a phages and publicly available Stx2a phages from O145:H25 and O145:H28 STEC, isolated from HUS cases in the USA and a hemorrhagic diarrhea case from Japan, respectively. However, low similarity was seen when comparing the Norwegian O145:H25 Stx2a phage to Stx2a phages from STEC of other serotypes. In all the Norwegian O145:H25 STEC, we identified a second phage or remnants of a phage (a shadow phage, 61 kbp) inserted at the same integration site as the Stx2a phage. The shadow phage shared similarity with the Stx2a phage, but lacked stx2a and harbored effector genes not present in the Stx2a phage. We identified a conserved Stx2a phage among the Norwegian O145:H25 STEC that shared integration site with a shadow phage in all isolates. Both phage and shadow phage harbored several virulence-associated genes that may contribute to the increased pathogenicity of O145:H25 STEC.

• Falk, Ragnhild Sørum; Mariampillai, Julian Eek; Prestgaard, Erik Edvard; Heir, Trond; Bodegard, Johan & Robsahm, Trude Eid [Show all 18 contributors for this article] (2021). The Oslo Ischaemia Study: cohort profile. BMJ Open. 11(10). doi: 10.1136/bmjopen-2021-049111. Full text in Research Archive Show summary

  Abstract Purpose The Oslo Ischaemia Study was designed to investigate the prevalence and predictors of silent coronary disease in Norwegian middle-aged men, specifically validating exercise electrocardiography (ECG) findings compared with angiography. The study has been important in investigating long-term predictors of cardiovascular morbidity and mortality, as well as investigating a broad spectrum of epidemiological and public health perspectives. Participants In 1972–1975, 2014 healthy men, 40–59 years old, were enrolled in the study. Comprehensive clinical examination included an ECG-monitored exercise test at baseline and follow-ups. The cohort has been re-examined four times during 20 years. Linkage to health records and national health registries has ensured complete endpoint registration of morbidity until the end of 2006, and cancer and mortality until the end of 2017. Findings to date The early study results provided new evidence, as many participants with a positive exercise ECG, but no chest pain (‘silent ischaemia’), did not have significant coronary artery stenosis after all. Still, they were over-represented with coronary disease after years of follow-up. Furthermore, participants with the highest physical fitness had lower risk of cardiovascular disease, and the magnitude of blood pressure responses to moderate exercise was shown to influence the risk of cardiovascular disease and mortality. With time, follow-up data allowed the scope of research to expand into other fields of medicine, with the aim of investigating predictors and the importance of lifestyle and risk factors. Future plans Recently, the Oslo Ischaemia Study has been found worthy, as the first scientific study, to be preserved by The National Archives of Norway. All the study material will be digitised, free to use and accessible for all. In 2030, the Oslo Ischaemia Study will be linked to the Norwegian Cause of Death Registry to obtain complete follow-up to death. Thus, a broad spectrum of additional opportunities opens.

• Ramstad, Silje; Brandal, Lin T.; Taxt, Arne Michael; Wasteson, Yngvild; Bjørnholt, Jørgen & Naseer, Mohammed Umaer (2021). Prevalence of genotypic antimicrobial resistance in clinical Shiga toxin-producing Escherichia coli in Norway, 2018 to 2020. Journal of Medical Microbiology. ISSN 0022-2615. 70(12). doi: 10.1099/jmm.0.001454. Full text in Research Archive Show summary

  Introduction. Shiga toxin-producing Escherichia coli (STEC) can cause severe to fatal disease in humans. Antimicrobial treatment is sometimes necessary, but contraindicated due to undesirable clinical outcome. However, recent studies have shown promising outcomes following antimicrobial treatment. Before the establishment of a possible antimicrobial treatment strategy for STEC infections, the prevalence of antimicrobial resistance in STEC needs to be determined. Gap Statement. The resistance status of Norwegian clinical STEC is not known and should be assessed. Aim. We aim to characterize genotypic antimicrobial resistance determinants in clinical STEC in Norway, and determine the prevalence of genotypic resistance in order to inform possible antimicrobial treatment options for STEC infections. Methodology. We included all clinical STEC submitted to the Norwegian Reference Laboratory from March 2018 to April 2020. All samples were whole-genome sequenced and screened for genotypic antimicrobial resistance,virulence determinants and plasmid incompatibility groups. We performed phylogenetic clustering of STEC by core-genome multi-locus sequence typing, and statistical association analyses between isolate characteristics and genotypic resistance. Results. A total of 459 STEC were analysed. For 385 (83.9 %) STEC we did not identify any antimicrobial resistance determinants. Seventy-four STEC (16.1 %) harboured antimicrobial resistance determinants against one or more antimicrobial classes. The most frequent genotypic resistance was identified against aminoglycosides (10.5 %). Thirty-nine STEC (8.5 %) had a multi-drug resistance (MDR) genotype. Genotypic resistance was more prevalent in non-O157 than O157 STEC (P=0.02). A positive association was seen between genotypic resistance and the low-virulent STEC O117:H7 phylogenetic cluster (no. 14) (P<0.001). Genotypic resistance was not significantly associated to high-virulent STEC. STEC O146:H28 and isolates harbouring the plasmid replicon type IncQ1 were positively associated with MDR. Conclusion. The overall prevalence of genotypic resistance in clinical STEC in Norway is low (16.1 %). Genotypic resistance is more prevalent in non-O157 strains compared to O157 strains, and not significantly associated to high-virulent STEC. Resistance to antimicrobials suggested for treatment, especially azithromycin is low and may present an empiric treatment alternative for severe STEC infections.

• Lossius, Astrid Haaskjold; Sundnes, Olav; Ingham, Anna Cäcilia; Edslev, Sofie Marie; Bjørnholt, Jørgen Vildershøj & Lilje, Berit [Show all 12 contributors for this article] (2021). Shifts in the Skin Microbiota after UVB Treatment in Adult Atopic Dermatitis. Dermatology. ISSN 1018-8665. 238(1), p. 109–120. doi: 10.1159/000515236. Full text in Research Archive Show summary

  &lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The pathophysiology in atopic dermatitis (AD) is not fully understood, but immune dysfunction, skin barrier defects, and alterations of the skin microbiota are thought to play important roles. AD skin is frequently colonized with &lt;i&gt;Staphylococcus aureus&lt;/i&gt; (&lt;i&gt;S. aureus&lt;/i&gt;) and microbial diversity on lesional skin (LS) is reduced compared to on healthy skin. Treatment with narrow-band ultraviolet B (nb-UVB) leads to clinical improvement of the eczema and reduced abundance of &lt;i&gt;S. aureus&lt;/i&gt;. However, in-depth knowledge of the temporal dynamics of the skin microbiota in AD in response to nb-UVB treatment is lacking and could provide important clues to decipher whether the microbial changes are primary drivers of the disease, or secondary to the inflammatory process. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; To map the temporal shifts in the microbiota of the skin, nose, and throat in adult AD patients after nb-UVB treatment. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Skin swabs were taken from lesional AD skin (&lt;i&gt;n&lt;/i&gt; = 16) before and after 3 treatments of nb-UVB, and after 6–8 weeks of full-body treatment. We also obtained samples from non-lesional skin (NLS) and from the nose and throat. All samples were characterized by 16S rRNA gene sequencing. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; We observed shifts towards higher diversity in the microbiota of lesional AD skin after 6–8 weeks of treatment, while the microbiota of NLS and of the nose/throat remained unchanged. After only 3 treatments with nb-UVB, there were no significant changes in the microbiota. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Nb-UVB induces changes in the skin microbiota towards higher diversity, but the microbiota of the nose and throat are not altered.

• Christensen, Ingrid; Haug, Jon Birger; Berild, Dag; Bjørnholt, Jørgen Vildershøj & Jelsness-Jørgensen, Lars-Petter (2020). Hospital physicians' experiences with procalcitonin - implications for antimicrobial stewardship; a qualitative study. BMC Infectious Diseases. 20(1). doi: 10.1186/s12879-020-05246-6. Full text in Research Archive Show summary

  Background. Procalcitonin is an inflammatory biomarker that is sensitive for bacterial infections and a promising clinical decision aid in antimicrobial stewardship programs. However, there are few studies of physicians’ experiences concerning the use of PCT. The objective of this study was to investigate whether hospital physicians’ experience with procalcitonin after 18 months of use can inform the PCT implementation in antimicrobial stewardship programs. Materials/methods. We deployed a qualitative approach using semi-structured interviews with 14 hospital physicians who had experience with procalcitonin in clinical practice. Interviews were audio-taped, transcribed verbatim and analysed using thematic analysis. Results. Physicians reported a knowledge gap, which made them uncertain about the appropriate procalcitonin use, interpretation, and trustworthiness. Simultaneously, the physicians experienced procalcitonin as a useful clinical decision aid but emphasised that their clinical evaluation of the patient was the most important factor when deciding on antibiotic treatment. Conclusions. Procalcitonin was regarded a helpful clinical tool, but the physicians called for more knowledge about its appropriate uses. Active implementation of unambiguous procalcitonin algorithms and physician education may enhance the utility of the test as an antimicrobial stewardship adjunct.

• Ramstad, Silje Nøstvedt; Taxt, Arne Michael; Naseer, Mohammed Umaer; Wasteson, Yngvild; Bjørnholt, Jørgen Vildershøj & Brandal, Lin Cathrine T. (2020). Effects of antimicrobials on Shiga toxin production in high-virulent Shiga toxin-producing Escherichia coli. Microbial Pathogenesis. ISSN 0882-4010. doi: 10.1016/j.micpath.2020.104636. Full text in Research Archive Show summary

  Purpose: Antimicrobial treatment of Shiga toxin-producing Escherichia coli (STEC) infections is controversial because antimicrobials may stimulate Shiga toxin (Stx) production, and thereby increase the risk of developing haemolytic uremic syndrome (HUS). Previous in vitro studies have shown this mainly in infections caused by STEC serotype O157:H7. The aim of this study was to investigate induction of Stx transcription and production in different serotypes of STEC isolated from severely ill patients, following their exposure in vitro to six different classes of antimicrobials. Methods: We investigated Stx transcription and production in 12 high-virulent STEC strains, all carrying the stx2a gene, of six different serotypes following their exposure to six classes of antimicrobials. Liquid cultures of the STEC strains were incubated with sub-inhibitory concentrations of the antimicrobials. We used reversetranscription quantitative PCR to measure the relative expression of Stx2a mRNA and an enzyme-linked immunosorbent assay to quantify Stx production. Results: In general the antibiotics tested showed only minor effects on transcriptional levels of Stx2a. Ciprofloxacin caused an increase of Stx production in all but two strains, while gentamicin, meropenem and azithromycin did not induce Stx production in any of the STEC strains examined. STEC O104:H4 was the serotype that in greatest extent responded to antimicrobial exposure with an increase of stx2a transcription and Stx production. Conclusion: Gentamicin, meropenem and azithromycin exposure did not result in elevated Stx production. We recommend that this finding is investigated further in the search for candidates for future antimicrobial treatment of STEC.

• Ruscio, Francesco Di; Guzzetta, Giorgio; Bjørnholt, Jørgen; Leegaard, Truls Michael; Moen, Aina Elisabeth Fossum & Merler, Stefano [Show all 7 contributors for this article] (2019). Quantifying the transmission dynamics of MRSA in the community and healthcare settings in a low-prevalence country. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 116(29), p. 14599–14605. doi: 10.1073/pnas.1900959116. Full text in Research Archive Show summary

  Methicillin-resistant Staphylococcus aureus (MRSA) is a primarily nosocomial pathogen that, in recent years, has increasingly spread to the general population. The rising prevalence of MRSA in the community implies more frequent introductions in healthcare settings that could jeopardize the effectiveness of infection-control procedures. To investigate the epidemiological dynamics of MRSA in a low-prevalence country, we developed an individual-based model (IBM) reproducing the population’s sociodemography, explicitly representing households, hospitals, and nursing homes. The model was calibrated to surveillance data from the Norwegian national registry (2008–2015) and to published household prevalence data. We estimated an effective reproductive number of 0.68 (95% CI 0.47–0.90), suggesting that the observed rise in MRSA infections is not due to an ongoing epidemic but driven by more frequent acquisitions abroad. As a result of MRSA importations, an almost twofold increase in the prevalence of carriage was estimated over the study period, in 2015 reaching a value of 0.37% (0.25–0.54%) in the community and 1.11% (0.79–1.59%) in hospitalized patients. Household transmission accounted for half of new MRSA acquisitions, indicating this setting as a potential target for preventive strategies. However, nosocomial acquisition was still the primary source of symptomatic disease, which reinforces the importance of hospital-based transmission control. Although our results indicate little reason for concern about MRSA transmission in low-prevalence settings in the immediate future, the increases in importation and global circulation highlight the need for coordinated initiatives to reduce the spread of antibiotic resistance worldwide.

• Berdal, Jan Erik; Follin-Arbelet, Benoit & Bjørnholt, Jørgen Vildershøj (2019). Experiences from multiplex PCR diagnostics of faeces in hospitalised patients: Clinical significance of Enteropathogenic Escherichia coli (EPEC) and culture negative campylobacter. BMC Infectious Diseases. 19(1). doi: 10.1186/s12879-019-4271-1. Full text in Research Archive Show summary

  Background In hospitalised patients with diarrhoea a positive campylobacter stool Polymerase Chain Reaction (PCR) test with negative culture results as well as Enteropathogenic Escherichia coli (EPEC) positive stool PCRs, challenges the clinician and may lead the unexperienced clinician astray. The aim of the study was to elucidate the clinical significance of positive Campylobacter and/or EPEC test results in hospitalised patients with diarrhoea. Methods We conducted a retrospective case-case study. Case groups with 1) EPEC only and 2) EPEC in combination with any other pathogen in the PCR multiplex array, 3) PCR positive/culture negative Campylobacter, and 4) PCR positive/culture positive Campylobacter were compared. Medical records were reviewed and cases classified according to pre-specified clinical criteria as infectious gastroenteritis or non-infectious causes for diarrhoea. We analyzed the association between laboratory findings (the 4 subgroups) and the pre-specified clinical classification. We further sequenced culture negative campylobacter samples and tested EPEC for bundle forming pilus A (bfpA) gene, distinguishing typical from atypical EPEC. Results A total of 291 patients were included, 169 were PCR positive for Campylobacter and 122 for EPEC. For both pathogens, co-infections were more common in culture negative/PCR positive samples than in culture positive samples. Clinical characteristics differed significantly in and between groups. Campylobacter culture positive patients had very high prevalence of characteristics of acute infectious gastroenteritis, whereas patients with PCR positive test results only often had an alternative explanation for their diarrhoea. Culture positives were almost exclusively C. jejuni/coli, whereas in culture negatives, constituting a third of the total PCR positives, C. concisus was the most frequent species. The vast majority of EPEC only positives had documented non-infectious factors that could explain diarrhoea. The EPEC co-infected group mimicked the culture positive campylobacter group, with most patients fulfilling the infectious gastroenteritis criteria. Conclusions In hospitalised patients, positive PCR results for campylobacter and EPEC should be interpreted in a clinical context after evaluation of non-infectious diarrhoea associated conditions, and cannot be used as a stand-alone diagnostic tool.

• Dahl, Cecilie; Stigum, Hein; Valeur, Jørgen; Iszatt, Nina; Lenters, Virissa Claire & Peddada, Shyamal [Show all 10 contributors for this article] (2018). Preterm infants have distinct microbiomes not explained by mode of delivery, breastfeeding duration or antibiotic exposure. International Journal of Epidemiology. ISSN 0300-5771. 47(5), p. 1658–1669. doi: 10.1093/ije/dyy064. Full text in Research Archive
• Ruscio, Francesco Di; Bjørnholt, Jørgen; Larssen, Kjersti Wik; Leegaard, Truls Michael; Moen, Aina Elisabeth Fossum & Blasio, Birgitte Freiesleben De (2018). Epidemiology and spa-type diversity of meticillin-resistant Staphylococcus aureus in community and healthcare settings in Norway. Journal of Hospital Infection. ISSN 0195-6701. doi: 10.1016/j.jhin.2017.12.019. Full text in Research Archive Show summary

  Background: There has been a marked increase in the incidence of meticillin-resistant Staphylococcus aureus (MRSA) during the past decade in Norway; a country with one of the lowest prevalence rates and an active ‘search-and-destroy’ policy applied to hospital settings. Aim: To characterize the trends of notification rates of community-associated (CA) and healthcare-associated (HA) MRSA in Norway, and explore the diversity and circulation of MRSA spa types within and outside healthcare settings. Methods: A registry-based study on notified MRSA infections and colonizations was conducted in Norway between 2006 and 2015. The diversity and abundance of CA- and HA-MRSA spa types were compared using novel ecological diversity measures (Hill numbers). Findings: During the study period, the monthly notification rate increased 6.9-fold and 1.8-fold among CA- and HA-MRSA, respectively; the increase was steeper among colonizations than infections. In both settings, the distribution of spa types was uneven, with a few dominant spa types and many singletons. The spa-type diversity of CA-MRSA was higher than HA-MRSA in terms of different types (685 vs 481), and increased during the study period. However, the diversity associated with the dominant spa types was similar and remained stable. A high overlap of spa types was estimated between the settings; spa-t002, t019 and t008 were the most common. Conclusion: The present findings suggest a strong connection between CA- and HA-MRSA epidemiology in Norway. If the fast-growing trend of CA-MRSA continues in the years to come, it may challenge current guidelines and infection control of MRSA in healthcare environments.

• Johnsen, Bjørn Odd; Handal, Nina; Meisal, Roger; Bjørnholt, Jørgen; Gaustad, Peter & Leegaard, Truls Michael (2017). erm gene distribution among Norwegian Bacteroides isolates and evaluation of phenotypic tests to detect inducible clindamycin resistance in Bacteroides species. Anaerobe. ISSN 1075-9964. 47, p. 226–232. doi: 10.1016/j.anaerobe.2017.06.004. Full text in Research Archive
• Ruscio, Francesco Di; Bjørnholt, Jørgen; Leegaard, Truls Michael; Moen, Aina Elisabeth Fossum & Blasio, Birgitte Freiesleben De (2017). MRSA infections in Norway: A study of the temporal evolution, 2006-2015. PLOS ONE. 12(6). doi: 10.1371/journal.pone.0179771. Full text in Research Archive Show summary

  Background: Norway has one of the lowest prevalences of methicillin-resistant Staphylococcus aureus (MRSA) infections in the world. This study exploits the extensive data on MRSA infections in the Norwegian surveillance system to investigate the important factors defining the MRSA epidemiology. Methods: We performed a quasi-Poisson regression of the monthly notification rate (NR) of MRSA infections reported from January 2006 to December 2015, comparing the time trend among people with an immigrant vs. Norwegian background and domestic vs. imported infections, stratified by age groups. Findings: A total of 5289 MRSA infections were reported during the study period, of which 2255 (42·6%) were acquired in Norway, 1370 (25·9%) abroad, and 1664 (31·5%) with an unknown place of acquisition. Overall, the monthly NR increased significantly from 2006 to 2015 (+0·8% each month). The monthly increase in immigrants (+1·3%) was steeper than that in people with a Norwegian background (+0·6%). There was a significant growth (+0·4%) in the rate of domestically acquired infections, however, the NR of infections acquired abroad increased faster (+0·8%). For both imported and domestic infections, the increase occurred in persons aged < 70 years. Interpretation: Our analysis suggests that immigration and importation, especially among persons aged < 40 years, represent important factors for the increasing notification rate of MRSA infections in Norway.

• Samuelsen, Ørjan; Overballe-Petersen, Søren; Bjørnholt, Jørgen; Brisse, Sylvain; Doumith, Michel & Woodford, Neil [Show all 10 contributors for this article] (2017). Molecular and epidemiological characterization of carbapenemase-producing Enterobacteriaceae in Norway, 2007 to 2014. PLOS ONE. 12(11). doi: 10.1371/journal.pone.0187832. Full text in Research Archive Show summary

  The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) is increasing worldwide. Here we present associated patient data and molecular, epidemiological and phenotypic characteristics of all CPE isolates in Norway from 2007 to 2014 confirmed at the Norwegian National Advisory Unit on Detection of Antimicrobial Resistance. All confirmed CPE isolates were characterized pheno- and genotypically, including by whole genome sequencing (WGS). Patient data were reviewed retrospectively. In total 59 CPE isolates were identified from 53 patients. Urine was the dominant clinical sample source (37%) and only 15% of the isolates were obtained from faecal screening. The majority of cases (62%) were directly associated with travel or hospitalization abroad, but both intra-hospital transmission and one inter-hospital outbreak were observed. The number of CPE cases/year was low (2–14 cases/year), but an increasing trend was observed. Klebsiella spp. (n = 38) and E. coli (n = 14) were the dominant species and bla_KPC (n = 20), bla_NDM (n = 19), bla_OXA-48-like (n = 12) and bla_VIM (n = 7) were the dominant carbapenemase gene families. The CPE isolates were genetically diverse except for K. pneumoniae where clonal group 258 associated with bla_KPC dominated. All isolates were multidrug-resistant and a significant proportion (21%) were resistant to colistin. Interestingly, all bla_OXA-48-like, and a large proportion of bla_NDM-positive Klebsiella spp. (89%) and E. coli (83%) isolates were susceptible in vitro to mecillinam. Thus, mecillinam could have a role in the treatment of uncomplicated urinary tract infections caused by OXA-48- or NDM-producing E. coli or K. pneumoniae. In conclusion, the impact of CPE in Norway is still limited and mainly associated with travel abroad, reflected in the diversity of clones and carbapenemase genes.

• Blomfeldt, Anita; Eskesen, Arne N; Aamot, Hege Vangstein; Leegaard, Truls Michael & Bjørnholt, Jørgen (2016). Population-based epidemiology of Staphylococcus aureus bloodstream infection: clonal complex 30 genotype is associated with mortality. European Journal of Clinical Microbiology and Infectious Diseases. ISSN 0934-9723. 35(5), p. 803–813. doi: 10.1007/s10096-016-2601-4. Full text in Research Archive
• Grøntvedt, Carl Andreas; Elstrøm, Petter; Stegger, Marc; Skov, Robert L; Andersen, Paal Skytt & Larssen, Kjersti Wik [Show all 13 contributors for this article] (2016). Methicillin-resistant Staphylococcus aureus CC398 in humans and pigs in Norway: A "One Health" perspective on introduction and transmission. Clinical Infectious Diseases. ISSN 1058-4838. 63(11), p. 1431–1438. doi: 10.1093/cid/ciw552. Full text in Research Archive
• Blomfeldt, Anita; Aamot, Hege Vangstein; Eskesen, Arne N; Monecke, Stefan; White, Richard & Leegaard, Truls Michael [Show all 7 contributors for this article] (2016). DNA microarray analysis of Staphylococcus aureus causing bloodstream infection: bacterial genes associated with mortality? European Journal of Clinical Microbiology and Infectious Diseases. ISSN 0934-9723. 35(8), p. 1285–1295. doi: 10.1007/s10096-016-2663-3. Full text in Research Archive
• Mandal, Siddhartha; Godfrey, Keith M.; McDonald, Daniel; Treuren, Will V.; Bjørnholt, Jørgen & Midtvedt, Tore [Show all 12 contributors for this article] (2016). Fat and vitamin intakes during pregnancy have stronger relations with a proinflammatory maternal microbiota than does carbohydrate intake. Microbiome. 4. doi: 10.1186/s40168-016-0200-3. Full text in Research Archive Show summary

  Background Although diet is known to have a major modulatory influence on gut microbiota, knowledge of the specific roles of particular vitamins, minerals, and other nutrients is limited. Modulation of the composition of the microbiota in pregnant women is especially important as maternal microbes are transferred during delivery and initiate the colonization process in the infant. We studied the associations between intake of specific dietary nutrients during pregnancy and gut microbiota composition. Methods Utilizing the Norwegian NoMIC cohort, we examined the relations between intakes of 28 dietary macro- and micronutrients during pregnancy, derived from food frequency questionnaires administered to 60 women in the second trimester, and observed taxonomic differences in their gut microbiota four days after delivery (assessed through Illumina 16S rRNA amplicon analysis). Results Higher dietary intakes of fat-soluble vitamins, especially vitamin D, were associated with reduced microbial alpha diversity (p value <0.001). Furthermore, using recently developed statistical methodology, we discovered that the variations in fat-soluble vitamins, saturated and mono-unsaturated fat, and cholesterol intake, were associated with changes in phyla composition. Specifically, vitamin D, mono-unsaturated fat, cholesterol, and retinol were associated with relative increases in Proteobacteria, which is a phylum known to encompass multiple pathogens and to have pro-inflammatory properties. In contrast, saturated fat, vitamin E, and protein were associated with relative decreases in Proteobacteria. Conclusions The results in this article indicate that fats and fat-soluble vitamins are among the most potent dietary modulators of gut microbiota in mothers. The shifts in microbiota due to diet need to be further studied alongside gut microbiota changes during pregnancy to better understand the impact on infant gut microbiota.

• Bentele, Horst; Bergsaker, Marianne A Riise; Hauge, Siri Helene & Bjørnholt, Jørgen (2014). Vaccination coverage for seasonal influenza among residents and health care workers in Norwegian nursing homes during the 2012/13 season, a cross-sectional study. BMC Public Health. 14(1). doi: 10.1186/1471-2458-14-434. Full text in Research Archive
• Berdal, Jan Erik; Haagensen, Rolf E; Ranheim, Trond Egil & Bjørnholt, Jørgen (2014). Nosocomial candidemia; risk factors and prognosis revisited; 11 years experience from a Norwegian secondary hospital. PLOS ONE. 9(7). doi: 10.1371/journal.pone.0103916. Full text in Research Archive
• Skjeldestad, Finn Egil; Bjørnholt, Jørgen; Gran, Jon Michael & Eriksen, Hanne-Merete (2014). The effect of antibiotic prophylaxis guidelines on surgical-site infections associated with cesarean delivery. International Journal of Gynecology & Obstetrics. ISSN 0020-7292. 128(2), p. 126–130. doi: 10.1016/j.ijgo.2014.08.018. Full text in Research Archive
• White, Richard; Bjørnholt, Jørgen; Baird, Donna D.; Midtvedt, Tore; Harris, Jennifer & Pagano, Marcello [Show all 12 contributors for this article] (2013). Novel Developmental Analyses Identify Longitudinal Patterns of Early Gut Microbiota that Affect Infant Growth. PLoS Computational Biology. ISSN 1553-734X. 9(5). doi: 10.1371/journal.pcbi.1003042. Full text in Research Archive Show summary

  It is acknowledged that some obesity trajectories are set early in life, and that rapid weight gain in infancy is a risk factor for later development of obesity. Identifying modifiable factors associated with early rapid weight gain is a prerequisite for curtailing the growing worldwide obesity epidemic. Recently, much attention has been given to findings indicating that gut microbiota may play a role in obesity development. We aim at identifying how the development of early gut microbiota is associated with expected infant growth. We developed a novel procedure that allows for the identification of longitudinal gut microbiota patterns (corresponding to the gut ecosystem developing), which are associated with an outcome of interest, while appropriately controlling for the false discovery rate. Our method identified developmental pathways of Staphylococcus species and Escherichia coli that were associated with expected growth, and traditional methods indicated that the detection of Bacteroides species at day 30 was associated with growth. Our method should have wide future applicability for studying gut microbiota, and is particularly important for translational considerations, as it is critical to understand the timing of microbiome transitions prior to attempting to manipulate gut microbiota in early life.

• Berdal, Jan Erik; Bjørnholt, Jørgen; Blomfeldt, Anita; Smith, Erichsen Nils & Bukholm, Geir (2007). Patterns and dynamics of airway colonisation in mechanically-ventilated patients. Clinical Microbiology and Infection (CMI). ISSN 1198-743X. 13. doi: 10.1111/j.1469-0691.2006.01678.x. Full text in Research Archive
• Berdal, Jan Erik; Smith, Erichsen Nils; Bjørnholt, Jørgen; Blomfeldt, Anita & Bukholm, Geir (2006). Does Pseudomonas aeruginosa colonization influence morbidity and mortality in the intensive care unit patient? Experience from an outbreak caused by contaminated oral swabs. Acta Anaesthesiologica Scandinavica. ISSN 0001-5172. 50, p. 1095–1102. Full text in Research Archive
• Stavem, Knut; Aaser, E.; Sandvik, L.; Bjørnholt, Jørgen Vildershøy; Erikssen, G & Thaulow, Erik [Show all 7 contributors for this article] (2005). Lung function, smoking and mortality in a 26-year follow-up of healthy middle-aged males. European Respiratory Journal. ISSN 0903-1936. 25. Full text in Research Archive Show summary

  Lung function has been associated with mortality after adjusting for other risk factors; however, few studies have adjusted for physical fitness and reported separate analyses according to smoking status. In 1972�1975, spirometry, clinical and physiological parameters were recorded in 1,623 apparently healthy males aged 40�59 yrs. After 26 yrs of follow-up, the current authors investigated the association between baseline lung function and mortality, adjusting for smoking, physical fitness and other potential factors. By 2000, 615 individuals (38%) had died, with 308 (50%) of these deaths from cardiovascular (CV) causes. Forced expiratory volume in one second was a predictor of all-cause mortality (risk ratio (RR) 1.10 per reduction of 10%) after adjusting for smoking, physical fitness, age, systolic blood pressure, body mass index and serum cholesterol. The corresponding multivariate RR was 1.07 for CV causes and 1.34 for respiratory death. In conclusion, in stratified analyses among current and former smokers, forced expiratory volume in one second % predicted was a strong independent predictor of all-cause mortality and respiratory death among current smokers. Forced expiratory volume in one second % predicted was not associated with mortality among never-smokers. Prospective population studies have reported pulmonary function to be an independent predictor of all-cause and cardiovascular (CV) mortality when adjusting for a variety of confounders or known risk factors. Poor lung function, measured as forced expiratory volume in one second (FEV1), is also associated with increased mortality from respiratory diseases and malignancies. The mechanism for the relationship between lung function and CV mortality remains largely unexplained. Various mechanisms for the association between lung function and CV mortality have been suggested, such as through systemic inflammation, autonomic dysfunction, physical inactivity, socio-economic status, residual confounding, or that lung function is an indicator of general health status or unmeasurable environmental or lifestyle influences. The impact of lung function on mortality and coronary heart disease 24 after adjustment for self-reported physical activity has been reported, although no studies of mortality have adjusted for objective measures of physical fitness. Few studies also have reported the association between lung function and mortality separately for smoking groups. In this study, the current authors aimed to assess the predictive value of pulmonary function for all-cause, CV and respiratory mortality after adjusting for a number of risk factors, including smoking status and physical fitness. In addition, the present authors intended to assess the association separately in groups with different smoking habits. This study presents data from a population of healthy middle-aged males with follow-up over 26 yrs.

• Bodegård, Lars Johan; Erikssen, Gunnar; Bjørnholt, Jørgen; Gjesdal, K; Liestøl, Knut & Erikssen, Jan Emil (2005). Reasons for terminating an exercise test provide independent prognostic information: 2014 apparently healthy men followed for 26 years. European Heart Journal. ISSN 0195-668X. 26, p. 1394–1401. Full text in Research Archive
• Berdal, Jan Erik; Skråmm, Inge; Mowinckel, P.; Gulbrandsen, Pål & Bjørnholt, Jørgen (2005). Use of rifampicin and ciprofloxacin combination therapy after surgical debridement in the treatment of early manifestation prosthetic joint infections. Clinical Microbiology and Infection (CMI). ISSN 1198-743X. 11, p. 843–845. Full text in Research Archive
• Bodegård, Lars Johan; Erikssen, Gunnar; Bjørnholt, Jørgen; Gjesdal, Knut; Thelle, Dag Steinar & Erikssen, Jan Emil (2004). Symptom-limited exercise testing, ST depressions and long-term coronary heart disease mortality in apparently healthy middle-aged men. Journal of Cardiovascular Risk. ISSN 1350-6277. 11, p. 320–327. Full text in Research Archive Show summary

  Background Previous studies have shown that ST-depressions >1.0 mm during or post exercise increase long term risk of dying from coronary heart disease (CHD), needing a coronary artery bypass grafting (CABG) or developing acute myocardial infarction (AMI) in healthy men. In the present prospective cohort study we investigate whether less marked ST-depressions may influence CHD-mortality, incidence of AMI, needing a CABG or having a nonfatal stroke. Methods During 1972-75, 2014 men aged 40-59 years, free from somatic diseases and not using any drugs, underwent an examination program including case history, clinical examination, various blood tests and a symptom limited exercise ECG-test. ECG was registered during exercise and at 30 seconds, 1, 2, 3 and 5 minutes post exercise. The possible prognostic impact of ST-changes of 0.50-0.99 mm and >1.00 mm compared to normal ST-segments were studied separately and combined. Horizontal, downsloping and slowly upsloping ST-segment pattern were combined. Results After adjustment for age, smoking, blood pressure, cholesterol, maximal heart rate, left ventricular hypertrophy and physical fitness ST-depressions &#8805;0.50 mm � during and/or post exercise � were associated with a 1.47-fold (95% CI 1.10 � 1.95) and1.54-fold (95% CI of 1.17 � 2.04) increased 26 years risk of CHD-mortality respectively. The same ST-changes also increased 22 years risk of developing nonfatal AMI or needing CABG but not developing nonfatal stroke. Conclusions Even an ST-depression >0.50 mm during and/or post exercise increases the long term risk of CHD-death, developing an AMI or needing CABG. No assosiation was found between ST-changes and incidence of nonfatal strokes.

• Erikssen, Gunnar; Bodegård, Lars Johan; Bjørnholt, Jørgen; Liestøl, Knut; Thelle, Dag Steinar & Erikssen, Jan Emil (2004). Exercise testing of healthy men in a new perspective: from diagnosis to prognosis. European Heart Journal. ISSN 0195-668X. 25, p. 978–986. Full text in Research Archive
• Bodegård, Lars Johan; Erikssen, Gunnar; Bjørnholt, Jørgen; Thelle, Dag Steinar & Erikssen, Jan Emil (2004). Possible angina detected by the WHO angina questionnaire in apparently healthy men with a normal exercise ECG: coronary heart disease or not? A 26 year follow up study. Heart. ISSN 1355-6037. 90, p. 627–632. Full text in Research Archive
• Bjørnholt, Jørgen; Erikssen, Gunnar; Kjeldsen, Sverre Erik; Bodegard, Johan; Thaulow, Erik & Erikssen, Jan Emil (2003). Fasting blood glucose is independently associated with resting and exercise blood pressure and development of elevated blood pressure. Journal of Hypertension. ISSN 0263-6352. p. 1383–1389. Full text in Research Archive
• Bodegard, Johan; Erikssen, Gunnar; Sandvik, Leiv; Kjeldsen, Sverre Erik; Bjørnholt, Jørgen & Erikssen, Jan Emil (2002). Early Versus Late Morning Measurement of Blood Pressure in Healthy Men. A Potential Source of Measurement Bias? Blood Pressure. ISSN 0803-7051. 6(11), p. 366–370. Full text in Research Archive
• Bjørnholt, Jørgen; Erikssen, Gunnar; Liestøl, Knut; Jervell, Jakob Anton; Thaulow, Erik & Erissen, J. (2000). Type 2 diabetes and maternal family history: an impact beyond slow glucose removal rate and fasting hyperglycemia in low-risk individuals? Results from 22 years of follow-up of healty nondiabetic men. Diabetes Care. ISSN 0149-5992. 23(9), p. 1255–1259. Full text in Research Archive
• Erikssen, Gunnar; Liestøl, Knut; Bjørnholt, Jørgen; Stormorken, Helge; Thaulow, Erik & Erikssen, Jan Emil (2000). Erythrocyte sedimentation rate as a predictor of coronary heart disease mortality. Erythrocyte sedimentation rate as a predictor of coronary heart diseaes mortality.. 120, p. 1011–1014. Full text in Research Archive
• Erikssen, Gunnar; Liestøl, Knut; Eriksen, Jan; Bjørnholt, Jørgen & Thaulow, Erik (2000). Hypothesis: The recent decline in the coronary heart disease mortality - mainly a shift from fatal to non-fatal events? Scandinavian Cardiovascular Journal. ISSN 1401-7431. p. 34–34. Full text in Research Archive
• Bjørnholt, Jørgen; Sandvik, Leiv; Jervell, Jakob Anton & Eriksen, Jan (1999). Response to Bilkau et al. Fasting blood glucose and risk of cardiovascular disease. Diabetes Care. ISSN 0149-5992. p. 1383–1384. Full text in Research Archive
• Bjørnholt, Jørgen; Eriksen, G.; Aaser, Ellinor; Sandvik, Leiv; Nitter-Hauge, Sigurd L & Jervell, Jakob Anton [Show all 8 contributors for this article] (1999). Fasting blood glucose: An understimated risk foactor for cardiovascular deat. Results from a 22-year follow-up of healthy non-diabetic men. Diabetes Care. ISSN 0149-5992. 22, p. 45–49. Full text in Research Archive
• Bjørnholt, Jørgen; Eriksen, G.; Aaser, Ellinor; Sandvik, Leiv; Nitter-Hauge, Sigurd L & Jervell, Jakob Anton [Show all 8 contributors for this article] (1999). Fasting blood glucose: An underestimated risk factor for cardiovascular deat. Results from a 22-year follow-up of healthy non-diabetic men. Diabetes Care. ISSN 0149-5992. 22, p. 45–49. Full text in Research Archive
• Thaulow, Erik; Bjørnholt, Jørgen; Eriksen, Jan & Nitter-Hauge, Sigurd L (1996). Kan medisinsk antiischemisk behandling bedre overlevelsen ved stabil koronar sykdom. Hjerteforum. ISSN 0802-1465. p. 18–26. Full text in Research Archive
• Thaulow, Erik; Bjørnholt, Jørgen; Eriksen, Jan & Nitter-Hauge, Sigurd L (1996). Kan medisinsk antiischemisk behandling bedre overlevelsen ved stabil koronarsykdom? Hjerteforum. ISSN 0802-1465. 9, p. 18–26. Full text in Research Archive

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• Danielsen, Anders Skyrud; Johansen, Amalie; Sare, Miriam; Lim, Cherry; Bjørnholt, Jørgen & Furberg, Anne-Sofie [Show all 7 contributors for this article] (2026). The microbial winners and losers in all Norwegian blood cultures over two decades, 2005–2024. Full text in Research Archive Show summary

  Background Bacteraemia incidence and microbial epidemiology are evolving globally, and is likely influenced by demographic changes [1,2]. The Norwegian Surveillance System for Antimicrobial Resistance (NORM) provides an opportunity to assess long-term trends in bacteraemia and their drivers, as all findings in blood cultures from all microbiological laboratories nationally are reported to the system [3]. This study aimed to describe temporal changes in bacteraemia incidence and microbial composition in Norway from 2005 to 2024, contextualising trends with population-level indicators. Methods We analysed national data on deduplicated blood culture isolates from 2005 to 2024, using reports from NORM. Isolates were classified into 21 species categories. Blood culture positivity rates were estimated at seven hospitals, adjusting for catchment populations. Contextual indicators were retrieved from national registries. Temporal trends in incidence (per 100,000 population) were modelled using negative binomial regression, adjusted for population age structure (≥70 years). Calendar year was included as a restricted cubic spline to capture non-linear trends. Results We analysed a total of 319,149 blood culture isolates from 2005 to 2024, with a yearly increase from 10,964 in 2005 to 22,679 in 2024, corresponding to 238 to 409 per 100,000 population (71.7% increase). Blood culture positivity remained stable at approximately 6%. Escherichia coli increased by 64%, Klebsiella spp. by 146%, and Staphylococcus aureus by 70%. Streptococcus pneumoniae declined by 49%, from 22 to 11 per 100,000. Most species showed increased incidence, with Gram-negative organisms rising more than Gram-positives. Streptococcus dysgalactiae and the "other" Gram-positive and Gram-negative categories also increased substantially. The population aged ≥70 years grew by 37.7%, while hospital bed-days declined by 37.3%. Conclusion This study shows a steady rise in bacteraemia incidence in Norway over the two decades. The stability of blood culture positivity rates suggests that the observed trends may reflect a real increase in infection burden. The decline in S. pneumoniae may reflect the impact of childhood pneumococcal vaccination. The relative increase in Gram-negative organisms and some emerging species indicate an increasing diversity, possibly due to changes in the patient case-mix, with importance for treatment regimens.

• Danielsen, Anders Skyrud; Gu, Qingze; Fostervold, Aasmund; Eyre, David W. & Bjørnholt, Jørgen (2024). ‘Bloodstream infection’: A valuable concept we should keep in our toolbox. Journal of Infection. ISSN 0163-4453. 89(4). doi: 10.1016/j.jinf.2024.106236. Full text in Research Archive
• Danielsen, Anders Skyrud; Lim, Cherry; Yoon, Chang-Ho; Gran, Jon Michael; Kacelnik, Oliver & Eyre, David W. [Show all 7 contributors for this article] (2024). Excess mortality due to AMR in bacteraemias among cancer patients in Oxford and Oslo, 2008-2018. Full text in Research Archive
• Danielsen, Anders Skyrud; Kacelnik, Oliver & Bjørnholt, Jørgen Vildershøj (2023). Reasons for hope? The incidence of MRSA and VRE seems to have stabilised in Norwegian cancer patients. Full text in Research Archive
• Heim, Amalie von BT; Lunestad, Bjørn Tore; Janice, Jessin; Bjørnholt, Jørgen; Hegstad, Kristin & Svanevik, Cecilie Smith (2022). Enterococci in marine bivalves from Norway – where do they come from and should we be concerned? Full text in Research Archive
• Fraz, Mai Sasaki Aanensen; Dahle, Gry; Skaug, Kirsten Margrete; Jarraud, Sophie; Frye, Stephan Alfons & Bjørnholt, Jørgen [Show all 7 contributors for this article] (2022). Case report: A prosthetic valve endocarditis caused by Legionella bozemanae in an immunocompetent patient. Frontiers in Medicine. 9:1055465, p. 1–7. doi: 10.3389/fmed.2022.1055465. Full text in Research Archive Show summary

  Extrapulmonary infections with Legionella species are rare, but important to acknowledge. We report a case of infective endocarditis (IE) with Legionella bozemanae in a 66-year-old immunocompetent man with an aortic homograft. The diagnosis was made by direct 16S rRNA gene amplification from valve material, confirmed by a targeted Legionella -PCR in serum and the detection of L. bozemanae specific antibodies. To our knowledge, this is the first confirmed case of IE with L. bozemanae as causative pathogen. The infected aortic prosthesis was replaced by a homograft, and the patient was successfully treated with levofloxacin and azithromycin for 6 weeks.

• Blomfeldt, Anita; Lilje, Berit; Stegger, Marc & Bjørnholt, Jørgen (2019). Man or microbe? A pilot study exploring Staphylococcus aureus CC30 isolates from bloodstream infections and nasal carriers. Full text in Research Archive
• Blomfeldt, Anita & Bjørnholt, Jørgen Vildershøj (2017). S. aureus blodbaneinfeksjon – hvilken rolle spiller bakteriene? Indremedisineren. ISSN 1891-1617. Full text in Research Archive
• Grøntvedt, Carl Andreas; Elstrøm, Petter; Stegger, Marc; Skov, Robert L; Andersen, Paal Skytt & Larsen, Kjersti Wiik [Show all 13 contributors for this article] (2016). MRSA CC398 in humans and pigs in Norway – Introduction and transmission. Full text in Research Archive
• Dahl, Cecilie; Stigum, Hein; Valeur, Jørgen; Iszatt, Nina; Lenters, Virissa & Mandal, Siddhartha [Show all 9 contributors for this article] (2016). Preterm infants have distinct microbiomes, not explained by mode of delivery, less breastfeeding, or antibiotic exposure. Full text in Research Archive
• Bjørnholt, Jørgen; Kacelnik, Oliver & Eriksen, Hanne-Merete (2016). Re: Kumulert sum ved overvåking av postoperative sårinfeksjoner. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 136(2), p. 105–106. doi: 10.4045/tidsskr.15.1366. Full text in Research Archive
• Angen, Øystein; Stegger, Marc; Grøntvedt, Carl Andreas; Elstrøm, Petter; Bjørnholt, Jørgen & Andersen, Paal Skytt [Show all 12 contributors for this article] (2015). Whole genome sequencing of MRSA CC398 - indication of several introductions to Norway. Full text in Research Archive
• Larssen, Kjersti Wik; Marstein, Lillian; Eriksen, Sissel-Karin; Kilnes, Anne K.; Gran, Frode Width & Bergh, Kåre [Show all 9 contributors for this article] (2014). Methicillin resistant Staphylococcus aureus carrying mecC in Norway. Full text in Research Archive
• Bodegard, Johan; Erikssen, Gunnar; Bjørnholt, Jørgen; Thelle, Dag Steinar & Erikssen, Jan Emil (2003). Är oförklarade bröstsmärtor hos friska män farliga eller icke? Full text in Research Archive
• Bjørnholt, Jørgen; Aaser, Ellinor; Sandvik, Leiv; Nitter-Hauge, Sigurd L; Eriksen, G. & Eriksen, Jan [Show all 7 contributors for this article] (1997). Fasting blood glucose is an independent predictor for cardiovascular death, but not in all age groups. Full text in Research Archive
• Herrador, Bernardo Rafael Guzmán; Berg, Thale Cathrine; Bjørnholt, Jørgen; Elstrøm, Petter; Kacelnik, Oliver & Kapperud, Georg [Show all 11 contributors for this article] (2015). Utbrudd av smittsomme sykdommer i Norge i 2014. Nasjonalt folkehelseinstitutt, Divisjon for Smittevern. Full text in Research Archive
• Herrador, Bernardo Rafael Guzmán; Arnesen, Trude Margrete; Berg, Thale Cathrine; Bjørnholt, Jørgen; Elstrøm, Petter & Kacelnik, Oliver [Show all 11 contributors for this article] (2014). Utbrudd av smittsomme sykdommer i Norge. Årsrapport 2013. Folkehelseinstituttet. Full text in Research Archive Show summary

  I 2013 ble det varslet 198 utbrudd med totalt 3 833 rapporterte sykdomstilfeller. Antallet syke varierte fra 2 til 290 per utbrudd. Ved 62 av utbruddene var det mistanke om smitte fra næringsmidler, og halvparten av alle utbrudd (102) var varslet fra helseinstitusjoner. Type utbrudd Antall utbrudd Antall tilfeller Totalt Median og variasjon Helseinstitusjon 102 1 951 11 (2-290) Næringsmiddelbårne 62 1 103 10 (2-109) Andre 34 779 10 (2-91) Totalt 198 3 833 10 (2-290) For utbrudd i helseinstitusjoner var norovirus og meticillinresistent Staphylococcus aureus (MRSA) de hyppigst forekommende agens, med henholdsvis 72 og 8 utbrudd. Det vanligste agens angitt ved næringsmiddelbårne utbrudd var norovirus (13 utbrudd); etterfulgt av Salmonella, Campylobacter, enterohemoragisk E. coli (EHEC), Hepatitt A - virus og Shigella sonnei (to utbrudd hver). Det er antagelig fortsatt en stor underrapportering av utbrudd. Rask og mer fullstendig varsling av utbrudd gjør at sentrale myndigheter kan se det enkelte utbrudd i nasjonal sammenheng. De kan dermed danne seg et bilde av den epidemiologiske situasjon i landet som helhet, varsle internasjonale instanser dersom det er nødvendig og gi råd og informasjon der det er behov.

• Steinbakk, Martin; Sunde, Marianne; Urdal, Anne Margrete; Barkbu, Kjersti Nilsen; Sørum, Henning & Lunestad, Bjørn Tore [Show all 10 contributors for this article] (2014). Antibiotikaresistens - kunnskapshull, utfordringer og aktuelle tiltak. Rapport fra tverrsektoriell ekspertgruppe. Folkehelseinstituttet. Full text in Research Archive
• Herrador, Bernardo Guzman; Bentele, Horst; Berg, Thale Cathrine; Bjørnholt, Jørgen; Bruun, Tone & Elstrøm, Petter [Show all 12 contributors for this article] (2013). Utbrudd av smittsomme sykdommer i Norge i 2012. Årsrapport. Folkehelseinstituttet. ISSN 9788280825766. Full text in Research Archive

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