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Every day in hospitals around the world, millions of interspecialty referrals are made to obtain advice on the optimal care and management of patients. In the UK, the brunt of this work is undertaken by junior doctors with less clinical experience than the specialist colleagues to which they refer. A survey of 283 junior doctors revealed that colleagues were underconfident when making referrals and struggled to know which specialty to contact, how to reach the specialty and what clinical information to include in the referral. More concerningly, 10% of those surveyed had experienced bullying or belittling behaviours and verbal aggression from colleagues when referring.The aim of this project was to design and implement a referrals toolkit for junior doctors to improve confidence making referrals and time to interspecialty advice, to improve patient care. Process mapping to understand the constituents of good referrals was combined with a failure modes and effects analysis describing how referrals fail to identify areas for intervention.A specialty referrals guide with all specialty contact information was created at the trust, demonstrating an increase in junior doctor median confidence from 3/5 (n=20) to 5/5 (n=23) (p

Recently we described a novel di-benzene-pyrylium-indolene (BAS00127538) inhibitor of Lipid II. BAS00127538 (1-Methyl-2,4-diphenyl-6-((1E,3E)-3-(1,3,3-trimethylindolin-2-ylidene)prop-1-en-1-yl)pyryl-1-ium) tetrafluoroborate is the first small molecule Lipid II inhibitor and is structurally distinct from natural agents that bind Lipid II, such as vancomycin. Here, we describe the synthesis and biological evaluation of 50 new analogs of BAS00127538 designed to explore the structure-activity relationships of the scaffold. The results of this study indicate an activity map of the scaffold, identifying regions that are critical to cytotoxicity, Lipid II binding and range of anti-bacterial action. One compound, 6jc48-1, showed significantly enhanced drug-like properties compared to BAS00127538. 6jc48-1 has reduced cytotoxicity, while retaining specific Lipid II binding and activity against Enterococcus spp. in vitro and in vivo. Further, this compound showed a markedly improved pharmacokinetic profile with a half-life of over 13 hours upon intravenous and oral administration and was stable in plasma. These results suggest that scaffolds like that of 6jc48-1 can be developed into small molecule antibiotic drugs that target Lipid II.