Antibiotic Prescribing Patterns in Ghana, Uganda, Zambia and Tanzania Hospitals: Results from the Global Point Prevalence Survey (G-PPS) on Antimicrobial Use and Stewardship Interventions Implemented

Antimicrobial resistance (AMR) remains an important global public health issue with antimicrobial misuse and overuse being one of the main drivers. The Global Point Prevalence Survey (G-PPS) of Antimicrobial Consumption and Resistance assesses the prevalence and the quality of antimicrobial prescriptions across hospitals globally. G-PPS was carried out at 17 hospitals across Ghana, Uganda, Zambia and Tanzania. The overall prevalence of antimicrobial use was 50% (30–57%), with most antibiotics prescribed belonging to the WHO ‘Access’ and ‘Watch’ categories. No ‘Reserve’ category of antibiotics was prescribed across the study sites while antimicrobials belonging to the ‘Not Recommended’ group were prescribed infrequently. Antimicrobials were most often prescribed for prophylaxis for obstetric or gynaecological surgery, making up between 12 and 18% of total prescriptions across all countries. The most prescribed therapeutic subgroup of antimicrobials was ‘Antibacterials for systemic use’. As a result of the programme, PPS data are now readily available for the first time in the hospitals, strengthening the global commitment to improved antimicrobial surveillance. Antimicrobial stewardship interventions developed included the formation of AMS committees, the provision of training and the preparation of new AMS guidelines. Other common interventions included the presentation of findings to clinicians for increased awareness, and the promotion of a multi-disciplinary approach to successful AMS programmes. Repeat PPS would be necessary to continually monitor the impact of interventions implemented. Broader participation is also encouraged to strengthen the evidence base

Assessing the Impact of a Global Health Fellowship on Pharmacists’ Leadership Skills and Consideration of Benefits to the National Health Service (NHS) in the United Kingdom

Antimicrobial resistance (AMR) poses a global, public health concern that affects humans, animals and the environment. The UK Fleming Fund’s Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) scheme aimed to support antimicrobial stewardship initiatives to tackle AMR through a health partnership model that utilises volunteers. There is evidence to indicate that NHS staff participating in international health projects develop leadership skills. Running in parallel with the CwPAMS scheme was the first Chief Pharmaceutical Officer’s Global Health (CPhOGH) Fellowship for pharmacists in the UK. In this manuscript, we evaluate the impact, if any, of participation in the CwPAMS scheme and the CPhOGH Fellowship, particularly in relation to leadership skills, and consider if there are demonstrable benefits for the NHS. The 16 CPhOGH Fellows were invited to complete anonymised baseline and post-Fellowship self-assessment. This considered the impact of the Fellowship on personal, professional and leadership development. Senior colleagues were invited to provide insights into how the Fellows had performed over the course of the Fellowship. All Fellows responded to both the pre- and post-Fellowship questionnaires with a return of 100% (16/16) response rate. There was a significant improvement in Fellows’ perception of their confidence, teaching abilities, understanding of behaviour change, management and communication skills. However, there was no change in the Fellows’ attitude to work. Feedback was received from 26 senior colleagues for 14 of the CPhOGH Fellows. Overall, senior colleagues considered CPhOGH Fellows to progress from proficient/established competencies to strong/excellent when using the national pharmacy Peer Assessment Tool and NHS Healthcare Leadership Model. The majority (88%) of senior colleagues would recommend the Fellowship to other pharmacists. The analysis of the data provided suggests that this CPhOGH Fellowship led to the upskilling of more confident, motivated pharmacist leaders with a passion for global health. This supports the NHS’s long-term plan “to strengthen and support good compassionate and diverse leadership at all levels”. Constructive feedback was received for improvements to the Fellowship. Job satisfaction and motivation improved, with seven CPhOGH Fellows reporting a change in job role and five receiving a promotion

A New Mode of Mineralocorticoid Receptor Antagonism by a Potent and Selective Nonsteroidal Molecule*

Limitations of current steroidal mineralocorticoid receptor (MR) antagonists have stimulated the search for a new generation of molecules. We screened for novel nonsteroidal compounds and identified MR antagonists derived from the chemical class of dihydropyridines. Chemical optimization resulted in BR-4628, which displays high in vitro and in vivo MR potency as well as selectivity with respect to the other steroid hormone receptors and the L-type calcium channel. Biochemical studies demonstrated that BR-4628 forms complexes with MR that do not promote the recruitment of transcriptional co-regulators. Docking experiments, using the crystal structure of the MR ligand-binding domain in an agonist conformation, revealed that BR-4628 accommodates in the MR ligand-binding cavity differently in comparison with the classical steroidal MR antagonists. An alanine scanning mutagenesis approach, based on BR-4628 docking, allowed identifying its anchoring mode within the ligand-binding cavity. Altogether, we propose that BR-4628 is a bulky antagonist that inactivates MR through a passive mechanism. It represents the prototype of a new class of MR antagonists