Academic Editors: Tania Ayllón and Gustavo Ortiz-Díez Received: 28 January 2025 Revised: 21 February 2025 Accepted: 26 February 2025 Published: 5 March 2025 Citation: Wesangula, E.; Chizimu, J.Y.; Mapunjo, S.; Mudenda, S.; Seni, J.; Mitambo, C.; Yamba, K.; Gashegu, M.; Nhantumbo, A.; Francis, E.; et al. A Regional Approach to Strengthening the Implementation of Sustainable Antimicrobial Stewardship Programs in Five Countries in East, Central, and Southern Africa. Antibiotics 2025, 14, 266. https://doi.org/10.3390/ antibiotics14030266 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/). Article A Regional Approach to Strengthening the Implementation of Sustainable Antimicrobial Stewardship Programs in Five Countries in East, Central, and Southern Africa Evelyn Wesangula 1, * , Joseph Yamweka Chizimu 2 , Siana Mapunjo 3 , Steward Mudenda 2 , Jeremiah Seni 4 , Collins Mitambo 5 , Kaunda Yamba 6 , Misbah Gashegu 7 , Aquino Nhantumbo 8 , Emiliana Francis 3 , Nyambura Moremi 9 , Henry Athiany 10 and Martin Matu 1 1 East Central and Southern Africa Health Community, Arusha P.O. Box 1009, Tanzania; mmatu@ecsahc.org 2 Zambia National Public Health Institute, Antimicrobial Resistance Coordinating Committee, Lusaka 10101, Zambia; chizimuyjoseph@yahoo.com (J.Y.C.); freshsteward@gmail.com (S.M.) 3 Antimicrobial Resistance Coordinating Committee, Ministry of Health, Dodoma P.O. Box 743, Tanzania; smapunjo@yahoo.com (S.M.); emmyfra@yahoo.com (E.F.) 4 Department of Microbiology and Immunology, Weill-Bugando School of Medicine, Catholic University of Health and Allied Sciences, Mwanza P.O. Box 1464, Tanzania; senijj80@gmail.com 5 Antimicrobial Resistance Coordinating Committee, Ministry of Health, Lilongwe P.O. Box 30377, Malawi; cmitambo@gmail.com 6 ReAct Africa, Lusaka 10101, Zambia; kaundayamba@gmail.com 7 Rwanda Biomedical Center, Kigali P.O. Box 7162, Rwanda; misbah.gashegu@rbc.gov.rw 8 National Institute of Health, Maputo 1100, Mozambique; aquino.nhantumbo@ins.gov.mz 9 National Public Health Laboratory, Dar es Salaam P.O. Box 9083, Tanzania; nyamburasogone@gmail.com 10 Department of Statistics and Actuarial Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi P.O. Box 62000-00200, Kenya; henry.athiany@jkuat.ac.ke * Correspondence: ewesangula@ecsahc.org; Tel.: +254-721244868 Abstract: Background: Antimicrobial stewardship (AMS) programs optimize the use of antimicrobials and reduce antimicrobial resistance (AMR). This study evaluated the imple- mentation of AMS programs in Africa using a harmonized regional approach. Methods: This was an exploratory cross-sectional study across five countries involving 32 hospi- tals using an adapted Periodic National and Hospitals Assessment Tool from the World Health Organization (WHO) policy guidance on integrated AMS activities in human health. Results: This study found baseline scores for AMS core elements ranging from 34% to 79% at the baseline which improved to 58% to 92% at the endline. At baseline, Drugs and Therapeutics Committee (DTC) functionality in updating facility-specific medicines and medical devices ranged from 58% to 100%, and this ranged from 79 to 100% at endline. Classifying antibiotics by WHO AWaRe, classification ranged from 33% to 83% at baseline and 64% to 100% at endline. Leadership commitment scores were 47% at baseline and 66% at endline. Education and training scores were 42% and 63% at baseline and endline, respectively. Reporting and feedback scores were 34% at baseline and 58% at endline. Conclusions: Our study showed that understanding context and standardizing regional stewardship approaches enhanced cross-country learning and improved AMS implementa- tion. Although the challenges in Low- and Middle-Income Countries (LMICs) are similar, they vary by country and can be addressed by strengthening AMS regulatory frameworks and surveillance systems. Keywords: antimicrobial stewardship; antimicrobial resistance; core elements of AMS; regional approach; Africa Antibiotics 2025, 14, 266 https://doi.org/10.3390/antibiotics14030266