Table 1. Summary of main interventions to improve the use of antibiotics in Primary Care.

Year	Institutional support	Who designed and/or performed the interventions	Description
a) Activities at the local level (Aljarafe Area)
2011	Spanish Ministry of Health	Guide coordinating groupa and local Primary Care and Hospital managers	First publication of the antimicrobial therapeutic guide (book form and online).
	(Instituto de Salud Carlos III); European Development Regional Found (FEDER); Andalusian Regional Ministry of Health, Andalusian Health Technology Assessment Agency (AETSA)		Official presentation of the guide. Interdisciplinary conference, chaired by Primary Care and Hospital managers, with the participation of renowned speakers in the field of infectious diseases. Free delivery of guidelines for all attendees. The guide was sent by mail to all Primary Care Districts and Hospitals of the Andalusian Health Service.
		Local Primary Care and Hospital managers	Incorporation of the electronic version of the guide to the websites of Primary Care Centers and Hospital.
		Guide implementing groupb	First dissemination local plan of the guide. Educational meetings in Primary Care Centers (for general practitioners and paediatricians), Dental Care Unit, Emergency Unit, nursing homes with more than 80 residents, and Hospital Units (Emergency Service, Medicine Service, Urology Service, Ophtalmology Service) summarizing the importance of antimicrobial drug resistance, advantages of having a reference guide, the process of elaboration of the guide and participants, the description of the guide’s methodology and contents. For more details, look at ref 28. Number of meetings: 23. Duration of each activity: 1 hour.
2012	Spanish Ministry of Health	Guide coordinating groupa	Publication of second edition of the guide (online).
	(Instituto de Salud Carlos III); European Development Regional Found (FEDER); Andalusian Regional Ministry of Health, Andalusian Health Technology Assessment Agency (AETSA)	Guide implementing groupb	Second dissemination local plan. Educational meetings in Primary Care Centers and Hospital units (Gynecology, Spinal Injuries Unit, Pediatric Emergency Service, Otorhinolaryngology Service). For more details, look at ref 28. Content: recommendations for the treatment of infectious diseases in the community (mainly respiratory, urinary, skin, and dental infections) in the form of clinical cases. Number of meetings: 17. Duration of each activity: 1 hour.
		Guide coordinating groupa; and local Primary Care and Hospital managers	Incorporation of the guide to the Digital Medical History as an electronic decision support tool.
2013	Spanish Ministry of Health	Guide implementing groupb (microbiologists)	Third dissemination local plan. Educational meetings in Primary Care Centers. Content: contribution of the Microbiology Laboratory in the implementation of ASP in Primary Care, correct sampling for microbiological diagnosis, interpretation of antibiograms, local resistance data. Number of meetings: 9. Duration of each activity: 1 hour.
	(Instituto de Salud Carlos III); European Development Regional Fund (FEDER); Andalusian Regional Ministry of Health.
2016–2018	Andalusian Regional Ministry of Health; Andalusian Health Technology Assessment Agency (AETSA)	Guide coordinating groupa	Publication of third edition of the guide (online).
2018	Andalusian Regional Ministry of Health; Andalusian Health Technology Assessment Agency (AETSA); Spanish Medicines Agency and Health Products (AEMPS)	Guide coordinating groupa Local Primary Care and Hospital managers.	Official presentation conference, chaired by local Primary Care managers, Hospital managers, and regional and national authorities summarizing the role of the Aljarafe Guide as reference of regional ASP, and the Spanish Action Plan on Antimicrobial Resistance.
		PIRASOA program Coordinator.
		Spanish Action Plan on Antimicrobial Resistance Coordinator
b) Activities at the regional level (Andalucia)
2011	Andalusian Regional Ministry of Health; Andalusian Health Service (AHS).	General Direction of Health Care-AHS, and General Direction of Pharmacy-AHS	Official presentation of the guide: webcast through the portals of the AHS, Andalusian Center for Drug Information (CADIME), Andalusian Patient Safety Observatory, Andalusian website for Rationale Use of Drugs (Taqwin), website of the Agency for Health Technology Assessment (AETSA).
			Incorporation of the guide to website of Clinical Practice Guidelines of the Andalusian Health Service.
2012	Andalusian Regional Ministry of Health: Andalusian School of Public Health (EASP), and Andalusian Patient Safety Observatory; Andalusian Health Service (AHS).	Teaching teamc	Workshop for Primary Care and Hospital doctors, Primary Care and Hospital pharmacists, and microbiologists, members of the infection teams and commissions for the proper use of antibiotics. One of the objectives or this workshop was to form a group of experts at the regional level, to design activities related to the proper use of antimicrobials. Content: the management of most common infections and antibiotic prescribing, and key aspects about the implementation of Antimicrobial Stewardship Programmes (ASP). Duration of workshop: 8 hours. Workshop were centralized, performed at the EASP, and designed as “training of trainers”, so that the attendees could reproduce it in their Primary Care Centers and Hospitals. To this aim, attendees received a CD with the contents of the presentations and specific bibliography.
		General Direction of Health Care-AHS and General Direction of Pharmacy-AHS
		Teaching teamd	Workshop (3 in total) for general practitioners, Primary Care paediatricians and Primary Care pharmacists. Content: the management of most common infections in the community and antibiotic prescribing, taking as reference “The Aljarafe Guide”, and practical aspects about the implementation of ASP in Primary Care. Duration of workshop: 8 hours. Workshops were centralized, performed simultaneously in Seville, Granada and Antequera, and were designed as “training of trainers”, so that the attendees could reproduce it in their Primary Care Centers. To this aim, attendees received an email with the contents of the presentations and specific bibliography.
		Guide coordinating groupa
		General Direction of Health Care-AHS and General Direction of Pharmacy-AHS
			Workshops (3 in total) for Primary Care Pharmacists. Content: teachers provided knowledge, skills and experiences about the issues of antimicrobial resistance, and monitoring and evaluation of antimicrobial prescribing. Duration of workshops: 8 hours. Workshops were centralized, performed at the EASP, and designed as “training of trainers”, so that the attendees could reproduce them in their Primary Care Centers. To this aim, attendees received an email with the contents of the presentations and specific bibliography.
			Design and selection of indicators for monitoring the impact of ASP in Primary Care [26]
		Local Primary Care and Hospital managers	Incorporation of the guide (or an adaptation) to the Digital Medical History as an electronic decision support tool.
2013	Andalusian Regional Ministry of Health; Andalusian Health Service (AHS)	General Direction of Pharmacy-AHS	Incorporation of targets for antibiotic prescribing indicators linked to financial incentives in the annual agreements signed by Primary Care Areas and Clinical Units with the AHS.
		General Direction of Pharmacy-AHS	Monthly monitoring and feedback to managers and prescribers in Primary Care (general practitioners, paediatricians and dentists) on aggregated and individual rates of antibiotic prescribing. Benchmarking.
		Primary Care Pharmacy Services
2014	Andalusian Regional Ministry of Health	PIRASOA program Committee.	Implementation of institutional Antimicrobial Stewardship Program (ASP) (PIRASOA). Educational ASP comprised the creation of local antimicrobial multidisciplinary teams responsible for implementing interventions. The core of the programme was the counselling interviews. PIRASOA programme took “The Aljarafe Antimicrobial Therapeutic Guide” as reference guide for Primary Care. Since them, dissemination of Aljarafe guide updates was provided through the PIRASOA program. The PIRASOA elements can be consulted elsewhere [27, 29].
		Local ASP PIRASOA teams
c) Other activities at the regional or national level that may influence the rate of antimicrobials prescribing
Year	Who performed the intervention		Interventions
2011	Spanish Ministry of Health		Incorporation of the guide to the website of the Spanish National Health System (Guiasalud) [21]
2013	Spanish Ministry of Health; Spanish Agency for Medicines and Medical Devices (AEMPS)		Change of antimicrobials packaging [30]
2014	Spanish Ministry of Health; Spanish Agency for Medicines and Medical Devices (AEMPS)		Spanish Action Plan on Antimicrobial Resistance starts [25].
2016	Andalusian Ministry of Health		Introduction of 13-valent pneumococcal conjugate vaccine, in the Andalusian programme of childhood vaccination.
2017	Spanish Agency for Medicines and Medical Devices (AEMPS)		Spanish Action Plan on Antimicrobial Resistance adopted Aljarafe Guide as reference for ASP in Primary Care.

^aGuide coordinating group: a Primary Care Pharmacist, a Microbiologist, a Hospital Pharmacist, all of them, experts in infectious diseases and antibiotic management.

^bGuide implementing group: three Microbiologists, two Primary Care Pharmacists, two Hospital Pharmacists, four specialists in Family and Community Medicine (one of them from the Emergencies Hospital Service), two Pediatric specialists (one from Primary Care and the other from Pediatric Hospital Emergencies), two specialists in Internal Medicine, a specialist in Otorhinolaryngology, a dentist. They were all part of the team that developed the guide.

^cTeaching team: two members of the General Direction of Health Care (Andalucian Health Service (AHS)), the AHS General Director of Pharmacy, the Head of Service of Rational Drug Use (AHS), a Primary Care Pharmacists, an Infectious Diseases specialist. These professionals were selected by the AHS General Direction of Health Care and General Direction of Pharmacy for their expertise in infectious diseases and antibiotic management.

^dTeaching team: two members of the General Direction of Health Care (Andalucian Health Service (AHS)), the AHS General Director of Pharmacy, the Head of Service of Rational Drug Use (AHS), three Primary Care Pharmacists, three specialists in Family and Community Medicine; three Microbiologists, a Hospital Pharmacist, an Infectious Diseases specialist. These professionals were selected by the AHS General Direction of Pharmacy for their expertise in infectious diseases and antibiotic management.