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Objective Multiple myeloma is a haematological malignancy characterized by proliferation of monoclonal plasma cells in the bone marrow. Development of resistance and minimal residual disease remain challenging in the treatment of multiple myeloma. Transforming growth factor-β activated kinase 1 (TAK1) has recently gained attention as a potential drug target in multiple myeloma. This study aimed at determining the in vivo effects of TAK1-inhibitors in a Vκ*MYC multiple myeloma mouse model. Results We treated mice carrying Vκ*MYC multiple myeloma cells with the TAK1-inhibitors 5Z-7-oxozeaenol and NG25. There were tendencies towards increased survival for both inhibitors, but only NG25 prolonged survival significantly. However, this effect was limited, and no differences in disease burden were observed for any of the treatments. In conclusion, although TAK1-inhibitors might prolong survival somewhat, they do not prevent disease in the Vκ*MYC mouse model of multiple myeloma.

To characterise all bloodstream infections (BSIs) in a low antimicrobial resistance (AMR) prevalence setting with regard to the appropriateness of empirical antimicrobial therapy, compliance with the national clinical practice guideline, de-escalation practice and outcome. A retrospective observational study including patients aged ≥ 18 years admitted to a university hospital in central Norway with positive blood culture in 2019. We included 756 BSI episodes in our analysis. Empirical antimicrobial therapy was in accordance with the national guideline in 534 (70.6%), and not in accordance in 190 (25.1%) of the BSI episodes. There was a statistically significant association between compliance with the national guideline and concordant empirical antimicrobial therapy (p = .001). De-escalation of antimicrobial therapy was possible but not done in 217 (31.1%) of the BSI episodes. Variables identified as independent predictors of discordant empirical antimicrobial therapy included hospital department, type of empirical antimicrobial regimen, bacterial species, and AMR. Independent predictors of intra-hospital case fatality rate were coverage of empirical antimicrobial therapy, CCI-score, SAPS-II score, site of infection, and type of empirical antimicrobial regimen. Furthermore, the intra-hospital and long-term unadjusted all-cause case fatality rates were increased (p < .001, log-rank test for overall difference in survival) for the patients who received discordant empirical antimicrobial therapy. Our study shows that empirical antimicrobial therapy initiated in accordance with national guideline recommendations increases the likelihood of receiving concordant therapy. Discordant empirical antimicrobial therapy was associated with poorer outcomes, even in a setting with low AMR prevalence.