Inappropriate antibiotic usage is now a critical global health issue as it is a leading cause of antimicrobial resistance (AMR), which results in the reduced effectiveness of antimicrobials (Godman et al., 2021; Aldarhami, 2023; Baran et al., 2023; Ho et al., 2024). According to current estimates, AMR causes nearly 1.17 million deaths annually, with the number of deaths likely to more than double by 2050 if key issues and challenges are not addressed (Murray et al., 2022; Do et al., 2023). Infections caused by resistant bacteria increase morbidity and treatment costs, along with higher mortality and the risk of such infections spreading (Dadgostar, 2019; Wagenlehner and Dittmar, 2022; Spellberg et al., 2025; Wan et al., 2025). The impact of AMR is likely to be greater in low- and middle-income countries (LMICs), where the infection burden is higher and antimicrobial choices and usage are impacted by high levels of patient co-payments (Godman et al., 2021; Sulis et al., 2022; Khan et al., 2024; Lewnard et al., 2024; Sartorius et al., 2024; Saleem et al., 2025a).

In response to this critical public health issue, the World Health Organization (WHO, 2015) developed the Global Action Plan (GAP) on AMR, which led to the creation of National Action Plans (NAPs) aimed at encouraging countries to address the emerging public health threat of AMR (WHO, 2016). The purpose of the NAPs is to facilitate effective policy and stewardship measures to reduce the prevalence of AMR within each country (Godman et al., 2022; Willemsen et al., 2022; Charani et al., 2023). However, there have been concerns regarding the implementation of NAPs, especially in LMICs, due to resource constraints and shortage of trained personnel (Chua et al., 2021; Godman et al., 2022; Ohemu, 2022; Saleem et al., 2022). Notably, the fourth objective of NAPs emphasizes the development and implementation of clinical practice guidelines to promote the appropriate use of antimicrobials. These serve as tools for promoting rational prescribing practices and reducing the inappropriate use of antibiotics within countries. Clinical guidelines can be defined as documents that provide recommendations for clinical practice, aiming to minimize variability in care, particularly when scientific evidence is limited or when multiple therapeutic options are available (Steinberg et al., 2011; Johnson et al., 2021). The development and implementation of evidence-based guidelines support clinical decision-making by enhancing the quality of care, improving patient outcomes, and promoting the efficient use of resources (Sackett et al., 1996). The publication and implementation of antibiotic guidelines are regarded as important educational measures, especially for physicians in LMICs. This is because robust clinical guidelines are believed to significantly improve the quality of antibiotic prescribing across all sectors of care (Cooper et al., 2020; D’Arcy et al., 2021; Foxlee et al., 2021; Akhloufi et al., 2022; Boltena et al., 2023). As a result, adherence to published guidelines is increasingly incorporated into antimicrobial stewardship programs (ASPs) both in hospitals and primary care settings, often as part of agreed quality indicator targets (Versporten et al., 2018; Foxlee et al., 2021; Chigome et al., 2023; Funiciello et al., 2024; Lubanga et al., 2024). ASPs increasingly play a pivotal role in monitoring the implementation of national or regional guidelines to improve clinical outcomes across all sectors while minimizing the consequences of inappropriate antibiotic use (Nathwani et al., 2019; Brinkmann and Kibuule, 2020; Akhloufi et al., 2022; Siachalinga et al., 2022; Haseeb et al., 2023). ASPs in high-income countries (HICs) are often supported by electronic health records (EHRs)—digital systems that store patient medical information and can be integrated with clinical decision support tools. As a result, EHRs facilitate the monitoring of prescribing practices, facilitate audits, and help ensure adherence to national or institutional guidelines as part of ASPs. However, there have been concerns about implementing ASPs in LMICs due to resource limitations and personnel issues shortages; encouragingly, this is now beginning to change despite previous challenges (Cox et al., 2017; Brinkmann and Kibuule, 2020; Godman et al., 2021; Borde et al., 2022; Siachalinga et al., 2022).

Meanwhile, there is often a lack of national AMR surveillance, especially within LMICs, which limits the development of national evidence-based guidelines and the subsequent implementation of targeted policies to improve future antibiotic use (Woolf et al., 1999; Ohemu, 2022; Do et al., 2023; Okolie et al., 2023; Kiggundu et al., 2023; Mustafa et al., 2024). HICs often have access to resources for comprehensive guideline development, including local antimicrobial resistance data, systematic reviews, and advanced methodologies, including GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) (Barker et al., 2021). Conversely, LMICs frequently rely on expert opinions and internationally derived guidelines to help improve antibiotic prescribing, which may not be well-adapted to local AMR patterns and healthcare contexts. Moreover, due to resource constraints, implementing such guidelines or establishing such programs is more challenging in LMICs. In addition to this, adherence to national or international guidelines remains highly variable, especially across LMICs, leading to inappropriate and excessive use of antibiotics, which may be a reflection of concerns about the local relevance of adapted guidelines (Sulis et al., 2020; Thi et al., 2024; Wang et al., 2022; Mahmudul Islam et al., 2024).

Consequently, there is a need to evaluate the availability and scope of current national and international antibiotic guidelines. It is important to identify disparities in their development, adaptation, and implementation. These insights can inform strategies to improve guideline adherence, particularly by assessing the extent to which local AMR patterns are incorporated into guideline updates. We acknowledge that the WHO AWaRe book has recently been published, covering 35 common infections across healthcare sectors; this builds on the WHO AWaRe classification, which is part of the Essential Medicines List (Moja et al., 2024; WHO, 2022; Sharland et al., 2019). However, this guidance may require local adaption based on local resistance patterns. In addition, many existing local or national guidance may be outdated, highlighting the urgent need for updates—especially in light of the recent United Nations General Assembly (UN-GA) target, which calls for 70% of antibiotics used across sectors to come from the Access group (United Nations, 2024). We are also aware that the WHO AWaRe classification system is increasingly being used across studies, including those conducted in LMICs, to assess current antibiotic use patterns and set targets for ASPs—a trend that is expected to continue (Saleem et al., 2025a; Saleem et al., 2025b).

In view of the rising global threat of AMR, coupled with the variability in national and local antibiotic prescribing practices, the first objective of this review was to assess the availability, scope, and quality of current antibiotic prescribing guidelines across countries of varying income levels, specifically to identify gaps in guideline development and adaptation. This review also aimed to evaluate the degree to which current guidelines incorporate the WHO AWaRe book recommendations and address key components such as patient education, AMR surveillance, and stewardship strategies (Funiciello et al., 2024; Moja et al., 2024). By identifying these gaps and emphasizing the importance of locally adapted, evidence-based guidelines, this review seeks to contribute to ongoing global efforts to optimize antibiotic use, reduce the reliance on broad-spectrum antibiotics, and assist in achieving the NAP goals, especially in LMICs. This is viewed as essential for meeting the UN-GA target of reducing AMR and increasing the use of Access antibiotics (United Nations, 2024).

We retrieved 335 antibiotic prescribing guidelines, with the majority of data obtained directly from Google and official country websites. Of these, 181 guidelines met our inclusion criteria, provided sufficient information for our review, and were subsequently described in detail. Figure 2 illustrates the guideline selection process.

The general characteristics of the included antibiotic prescribing guidelines are summarized in Table 1 and Supplementary Table S1.

Since the development of antibiotic prescribing guidelines is usually an expensive and time-consuming process, requiring an expert’ team developed on the basis of the best available evidence, systematic reviews, and sound clinical understanding, there are likely to be disparities among countries with different income levels. HICs generally had more extensive and consistently updated clinical practice guidelines (CPGs) compared to LMICs, largely due to greater demand for care and better access to the resources, infrastructure, and expertise required for the development of such guidelines (Owolabi et al., 2018). For example, guidelines from the UK’s NICE, the US IDSA, and the Netherlands’ SWAB are based on rigorous methodologies, frequent updates, and comprehensive AMR integration (Greater Manchester, 2024; Tamma et al., 2024; Guideline Netherlands, 2024). Meanwhile, guidelines from LMICs, such as Nigeria’s National STGs and Ethiopia’s Standard Treatment Guidelines, particularly those from LICs, fell short in terms of coverage, quality, and content (Ministry of Health Ethiopia, 2014; Ministry of Health Nigeria, 2016).

As evidence-based decision-making has become a global standard for health interventions, the GRADE framework is increasingly used for the development of clinical guidelines (Baral et al., 2012; Park et al., 2015; Boon et al., 2021). HICs, supported by robust infrastructure and expert panels, have extensively implemented GRADE to provide transparency and methodological strength in recommendations (Bayona et al., 2017). For example, guidelines developed by the Infectious Diseases Society of America (IDSA), the American Thoracic Society (ATS), and UK bodies such as NICE and the British Thoracic Society (BTS) used GRADE consistently to integrate high-quality evidence and improve the implementation of antibiotic prescribing protocols (Jackson et al., 2020; NICE Guidelines, 2023; Smith et al., 2020; Gould et al., 2012a). In contrast, LMICs often rely on expert consensus due to limited resources, training, and access to evidence (Mzumara et al., 2023). Although several LMICs, including Pakistan, Ghana, Timor-Leste, and Rwanda, have developed evidence-based national treatment guidelines, their development is typically challenged by limited surveillance data, restricted funding, and suboptimal laboratory infrastructure (MMIDSP Guideline, 2022; Ministry of Health Ghana, 2017a; Hospital Guidelines Timor Leste, 2016; Ministry of Health Rwanda, 2022). These limitations also impede the routine use of systematic reviews and localized AMR data to inform prescribing.

Strengthening national efforts to combat AMR requires the development of guidelines that are both globally informed and locally applicable, as emphasized by the WHO. However, many LMICs lack the necessary infrastructure to support such efforts, particularly in terms of robust AMR surveillance systems. In these countries, either there is no routine national antibiogram reporting or the systems are fragmented and limited to isolated institutions (Gandra et al., 2020; Peters et al., 2024; Iskandar et al., 2021). A strong surveillance system typically includes nationwide coverage alongside standardized data collection, timely reporting, and integration with treatment guideline development (Nsubuga et al., 2011; Yang et al., 2020). The absence of these features in several LMICs undermines the ability to track resistance patterns and update empiric treatment guidelines accordingly (Gandra et al., 2020). Consequently, prescribers might find it challenging to match their practices with the WHO AWaRe book guidance; however, the AWaRe system provides a good starting point, particularly given its increasing use to monitor antibiotic use, including among LMICs, and the ongoing efforts to strengthen surveillance systems in these settings (Do et al., 2023; Iskandar et al., 2021; Tawfick et al., 2023). As a result, many LMICs are now working to implement more effective resistance surveillance in line with WHO goals. Local adaptation of the AWaRe guidance is key to support its use and enhance the effective management of infectious diseases. Local resistance trends contained within national and regional AMR surveillance data must inform first-line treatment choices, ensuring that guideline recommendations reflect local resistance profiles rather than relying merely on global trends (Mastrangelo et al., 2021). For instance, Rwanda’s susceptibility-guided empiric therapy and Kenya’s formulary mapping provide an example of how national guidance can be customized based on local data (Ministry of Health Rwanda, 2022; Gitaka et al., 2020). However, many LMICs lack comprehensive antibiograms, resulting in empiric overuse of broad-spectrum antibiotics, which should now be limited under the WHO AWaRe framework and guidance. This was evident in several guidelines included in our review. This included those from Nigeria, Ethiopia, and Malawi, which provided syndromic treatment recommendations without referencing local resistance data (Ministry of Health Ethiopia, 2014; Ministry of Health Malawi, 2015; Ministry of Health Nigeria, 2016). Addressing this gap involves investment in laboratory infrastructure and the training of healthcare professionals to correctly interpret and apply surveillance (Nishimura et al., 2008). This is important if LMICs are to achieve their AMR goals within their NAPs.

In HICs, AMS initiatives usually involve EHR audits, rapid diagnostics, and multidisciplinary stewardship teams to enhance appropriate antibiotic use. These technologies and institutional structures are usually lacking in LMICs. Scaling up such efforts across sectors will be critical to limiting unnecessary empiric antibiotic use and enhancing treatment outcomes (Bankar et al., 2022).

Financial barriers may also restrict the implementation of guidelines in LMICs as appreciable resources are typically needed in guideline development and adaptation (Baral et al., 2012). Technical requirements, ethical considerations, infrastructural barriers, and overburdened health systems, coupled with the lack of sufficient funding, typically prevent effective and meaningful implementation of clinical trials and other studies in LMICs to improve future antibiotic use. Consequently, it can be difficult to make conclusions regarding the applicability of guidelines that are applicable in HICs but could be a problem among LMICs (Stokes et al., 2016). To achieve success, strategies need to be adapted to overcome local resistance profiles, invest in AMS activities and diagnostics, and develop global partnerships to turn theory into practical and equitable solutions to address AMR in LMICs.

Educating key stakeholders, including prescribers and patients, about WHO AWaRe principles, including the importance of prioritizing Access over Watch antibiotics and avoiding unnecessary broad-spectrum antibiotic use, can strengthen AMS efforts at the population level (Saleem et al., 2025c). This is because patient education and counseling play crucial roles in improving antibiotic use, especially in LMICs, and enhancing healthcare outcomes (Saleem et al., 2025c). Counseling interventions often incorporate practical tools and follow-up care to support adherence. The British Thoracic Society’s 2020 Long-Term Macrolide Guidelines suggest written materials on therapy risks/benefits, whereas the ACCP 2006 Chronic Cough Guidelines advise patients on symptom relief and the self-limiting nature of viral bronchitis (Smith et al., 2020; Braman, 2006). Post-discharge instructions, including those in the SCCM 2020 Sepsis Guidelines, incorporate monitoring for secondary infections and corticosteroid-related side effects (Weiss et al., 2020). Effective counseling not only reduces unnecessary antibiotic use but also educates patients to engage in stewardship efforts, which include reducing requests and expectations for antibiotics for self-limiting viral infections for themselves or their children (Saleem et al., 2025c). In combination, these strategies connect clinical practice and community education, creating a unified front to reduce unnecessary antibiotic use and associated AMR, which is particularly important in LMICs (Mastrangelo et al., 2021).

We acknowledge that our study has limitations. We considered only English-language guidelines that were openly accessible, potentially leading to an overrepresentation of guidelines from HICs, particularly those in the European Region. There were also several countries for which we could not find guidance documents, and we encourage these countries to make their guidelines open-access and readily available to key stakeholder groups, including the general public. Similarly, our research might have missed documents depending on the search queries and engines used. However, we sought to include as many guiding documents as possible. Consequently, we believe our findings are robust and provide valuable direction for future work.

We found significant disparities in the availability, structure, and methodological rigor of guidelines across countries with different income levels. HICs commonly apply evidence-based frameworks such as GRADE, incorporate local AMR data, and have embedded stewardship strategies in the development of their antibiotic guidelines. This contrasts with many guidelines from LMICs, which remain generalized, outdated, and often rely on expert opinion due to limited resources, diagnostic capacity, and surveillance infrastructure. The incorporation of WHO AWaRe Book recommendations, as well as the extent to which current guidelines addressed patient education, AMR surveillance, and stewardship strategies, was also more evident in guidelines from HICs. In contrast, these components were often lacking in guidelines from LMICs, with patient education and surveillance data particularly underrepresented. The WHO AWaRe framework and Book provide a vital stepping stone, especially for LMICs; however, its successful implementation in LMICs relies on equity-led reforms. By prioritizing context-specific guidelines, increasing funding for diagnostics and stewardship, and fostering global partnerships, LMICs can transform the AWaRe framework and the associated guidance into practical and effective solutions to combat rising AMR rates. This approach will not only addresses current disparities but also help preserve the efficacy of antibiotics for future generations.