Development of a Triple Check-Point Antimicrobial Stewardship Intervention (TCP-AMSI) to ensure optimal initation, evaluation and de-escaltion of antimicrobial therapy in an Ethiopia tertiary care setting.

Background Antimicrobial resistance (AMR) is one of the top global public health and development threats. The WHO calculated that bacterial AMR will be directly responsible for 10 million global deaths in 2050. The overuse and misuse of antimicrobials in humans, next to animals and plants are the main drivers in the development of drug-resistant bacteria. The problem of AMR is aggravated by inadequate antimicrobial drug development; we are facing an empty antibiotic pipeline. AMR affects countries in all regions and all income levels, but its consequences are exacerbated by poverty and equality. Therefore, low- and middle-income countries, such as Ethiopia, are more affected. AMR makes infections harder to treat and makes other medical treatments, such as surgery and cancer chemotherapy, much riskier. Antimicrobial stewardship, bundling different types of interventions and approaches to warrant correct use of antimicrobials (antibacterials, antifungals and antivirals), is very important to combat emergence of antimicrobial resistance. In western Europe, antimicrobial stewardship is nowadays accepted as standard-of-care in hospital setting. However, low income countries, such as Ethiopia, antimicrobial stewardship is implemented in a very fragmented way or absent. Objectives The aim of this PhD project is to develop and implement a ‘triple check-point antimicrobial stewardship intervention’ in different tertiary care setting, ensuring optimal initiation, evaluation and de-escalation of antimicrobials in patients admitted with (severe) infections. With this, we aim to show that antimicrobial consumption will be reduced while maintaining the same efficacy (clinical cure rate) and safety. Methods The PhD proposal will be carried out in a ‘sandwich’ format. The study protocol, and especially the study intervention, will be prepared at the KU Leuven based on literature search and education different on antimicrobial stewardship interventions in Belgium. The study protocol will be developed as an interrupted time series analysis. The primary endpoint is reduction in antimicrobial consumption (DDD/100 patient days), efficacy, safety and emergence of antimicrobial resistance will be included as secondary endpoints. The study will be conducted in 4 tertiary care centres in Ethiopia; i.e. Ayder Comprehensive Specialized Hospital, Axum Comprehensive Specialized Hospital, Felege Hiwot Comprehensive Specialized Hospital, and Tikur Anbessa Comprehensive Specialized Hospital. These fouf specialized centres are located in different regions in Ethiopia, each have more than 250 beds and are equipped with adult and pediatric medical wards including ICUs. During the pre-intervention period, information on the pre-defined endpoints, the type and number of infectious diseases and antimicrobial treatment will be registered. Afterwards, the intervention will be implemented. The intervention, entitled ‘triple checkpoint-antimicrobial stewardship intervention, consists of a thorough check on antimicrobial treatment (choice, spectrum, dose, duration, de-escalation, discontinuation) at 3 timepoints (initiation, early maintenance and end of therapy). Clinicians and pharmacists will be trained on the intervention. In the post-intervention period, the same data will be acquired. After completion of the study, the data will be analyzed and finalized at the KU Leuven. A dissemination protocol, including barriers and facilitators, will be developed to allow dissemination in other Ethiopian hospitals.