Background: There is a need to examine the impact of increasingly prevalent antibiotic shortages on patient outcomes and on the emergence and spread of antimicrobial resistance. Objectives: To: (1) assess patterns and causes of shortages; (2) investigate the effect of shortages on health systems and patient outcomes; and (3) identify strategies for forecasting and managing shortages. Data sources: PubMed/MEDLINE, EMBASE, Scopus, and Web of Science. Study eligibility criteria: Studies published in English from January 2000 to July 2023. Participants health care, policy, and strategic teams managing and responding to shortages. Patient populations (adults and children) affected by shortages. Participants: Healthcare workers responding to and populations affected by antibiotic shortages. Interventions: Strategies, policies, and mitigation options for managing and responding to antibiotic drug shortages. Assessment of risk of bias: The methodological quality of included studies was reviewed using the most appropriate tool from Joanna Briggs institute critical appraisal tool for each study design. Methods of data synthesis: Data synthesis was qualitative and quantitative using descriptive statistics. Results: The final analysis included 74 studies (61/74, 82.4% high-income countries). Shortages were most reported for piperacillin-tazobactam (21/74, 28.4%), with most of the reported antibiotics being in the WHO Watch category (27/54, 51%). Frequent cause of shortages was disruption in manufacturing, such as supply of active pharmaceutical ingredients and raw materials. Clinical implications of shortages included increased length of hospital stay, treatment failure after using inferior alternative agents, and a negative impact on antimicrobial stewardship programmes (AMS). Robust economic impact analysis of shortages is unavailable. Successfully reported mitigation strategies were driven by AMS and infectious diseases teams in hospitals. Conclusions: Antibiotic shortages are directly or indirectly driven by economic viability and reliance on single source ingredients. The limited data on clinical outcomes indicates a mixed effect, with some infections becoming more difficult to treat, though there is no robust data on the impact of shortages on antimicrobial resistance. The mitigation strategies to manage shortages rely heavily on AMS teams. Avaneesh Kumar Pandey, Clin Microbiol Infect 2025;31:345 (c) 2024 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).