The feasibility of paramedics delivering antibiotic treatment pre-hospital to 'red flag' sepsis patients: a service evaluation.

BACKGROUND: Sepsis is associated with a 36% mortality rate, rising to 50% for septic shock. Currently, when an East Midlands Ambulance Service clinician recognises 'red flag' sepsis, only the oxygen and fluid elements of the 'Sepsis Six' care bundle are delivered, omitting the antibiotic therapy. For a patient in septic shock, every hour's delay in antibiotic therapy is associated with a 7.6% increase in mortality. Ambulance clinicians are therefore appropriately placed to assess and commence treatment at the earliest point of recognition. The aim of this evaluation was to assess the feasibility of training paramedics to recognise 'red flag' sepsis, obtain blood cultures and administer a broad spectrum antibiotic, meropenem, to patients in the pre-hospital environment. METHODS: A prospective six-month feasibility pilot evaluation was conducted in May 2016. Paramedics were trained and given access to a broad spectrum antibiotic, meropenem, along with a patient group direction to administer the antibiotic to 'red flag' sepsis patients. Training included sepsis recognition, taking of blood cultures and patient group direction compliance. RESULTS: Twenty paramedics volunteered and successfully completed the training. Of the 113 patients that were identified as 'red flag' sepsis, 107 (94.6%) were confirmed as infected by the receiving hospital. Ninety-eight blood samples were successfully drawn by study paramedics, with only seven (7.1%) reported as contaminated samples, compared with 8.5% of samples taken by staff in the receiving ED during the same time period. Ninety patients (80%) assessed by paramedics as meeting the criteria were treated with meropenem, and patient group direction compliance was 100%. CONCLUSION: Paramedics can safely deliver pre-hospital antibiotics to patients with 'red flag' sepsis and obtain blood cultures prior to administration, with a contamination rate comparable with local hospitals, following a short training course.

Discovery of a potent, selective, and orally bioavailable acidic 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitor: discovery of 2-[(3S)-1-[5-(cyclohexylcarbamoyl)-6-propylsulfanylpyridin-2-yl]-3-piperidyl]acetic acid (AZD4017).

Inhibition of 11ß-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. We report here the discovery of a nicotinic amide derived carboxylic acid class of inhibitors that has good potency, selectivity, and pharmacokinetic characteristics. Compound 11i (AZD4017) is an effective inhibitor of 11ß-HSD1 in human adipocytes and exhibits good druglike properties and as a consequence was selected for clinical development.