Benchmarking AWaRe: estimating optimal levels of AWaRe antibiotic use in 186 countries, territories and areas based on clinical infection and resistance burden

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSEnsuring appropriate access to essential antibiotics is a critical global public health goal. The UN General Assembly agreed that 70% of global antibiotic use should be WHO Access group. A standard method to estimate optimal antibiotic use based on burden of disease, resistance and local context is needed to inform national policies. MethodsUsing data from multiple global datasets, we clustered 186 countries, territories and areas (CTAs) into peer groups based on sociodemographic factors, infection and resistance incidence using a latent class model. Within each cluster, benchmark countries with low antibiotic use and infection mortality were identified. We estimated optimal Total DID given infection burden, Reserve DID based on relevant resistance burdens, Watch DID based on clinical infections requiring Watch antibiotics from the WHO AWaRe Book and Access DID as the residual volume. FindingsGlobally 43.0 billion DDDs (95%CI:35.4billion-57.7billion) of antibiotics in 2019 were needed in 186 CTAs, of which 76% would optimally be Access (95%CI:70%-82%). CTAs in lower-income clusters required more Watch and Reserve antibiotics than higher income CTAs. Among CTAs with actual use data available, 72% (48/67) of CTAs used more Total and 99% (66/67) used more Watch antibiotics than estimated optimal levels. ImplicationsWe present the first estimates of optimal AWaRe antibiotic levels for 186 CTAs. After accounting for country-specific needs, the UNGA 70% Access target is globally appropriate. AWaRe benchmarking enables CTAs to estimate under and overuse of AWaRe antibiotics to inform national policies. FundingThe ADILA Project funded by the Wellcome Trust [222051/Z/20/Z]. RO_SCPLOWESEARCHC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWINC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWCONTEXTC_SCPLOWO_ST_ABSEvidence before this studyC_ST_ABSMember states agreed at the 2024 United Nations General Assembly (UNGA) AMR meeting that the WHO AWaRe (Access, Watch, Reserve) system should underpin global antibiotic surveillance and that 70% of global use should be from the AWaRe Access group, while accounting for national contexts but did not agree any method for derived country-level targets. The WHO GLASS antimicrobial use (GLASS-AMU) surveillance system and other studies have reported observed antibiotic use. GLASS reports actual national medicine-level antibiotic use from 2015-2022 for 60 CTAs. The GRAM study (Browne, et al., 2021) modelled estimated total antibiotic use from 2000-2018 for 204 CTAs but were only able to estimate AWaRe antibiotic use for 76 CTAs where data from the commercial IQVIA MIDAS(R) database were available. Recent estimates from Klein et al. (2024) reported changes in antibiotic use from 2016 - 2023 for 67 CTAs in IQVIA MIDAS(R). Despite these studies quantifying estimates of current national medicine-level antibiotic use, there are very few estimates of what levels of antibiotic use are "optimal" both overall and by AWaRe group. We searched PubMed for studies from January 2015 through October 2025 on national-level antibiotic targets and AWaRe antibiotic policy using Boolean search terms. We identified few studies that estimated optimal levels of antibiotic use, but none for all AWaRe groups. As part of the Lancet AMR series, Mendelson et al. (2024) estimated expected total antibiotic use based on infection burden using the WHO AWaRe book guidance. This study developed a framework for estimating required Watch antibiotic use but did not provide comprehensive estimates for Access and Reserve use. Summan et al. (2025) estimated antibiotic needs for chronic obstructive pulmonary disease (COPD) and pneumonia in 20 CTAs using disease burden and bacterial aetiology. These estimates focused only on penicillins and cephalosporins and did not provide population based standardised measures to allow for cross-national comparison among CTAs. Mishra et al. (2025) estimated the gap in Reserve antibiotic treatment courses for use in carbapenem resistant Gram-negative infections in 8 countries using GRAM estimates and IQVIA sales data. While these studies have estimated expected antibiotic use for specific antibiotics or infections, there is no reported method to estimate optimal national levels of total and AWaRe antibiotic use. Added value of this studyWe developed a standard method for deriving optimal ranges of total and AWaRe antibiotic use in defined daily doses (DDD) per 1000 inhabitants per day (DID) accounting for national level infection and antibiotic resistance burden, population socio-demographics, national income, health system infrastructure and healthcare access using a benchmarking approach. Our study provides the first comprehensive estimates of optimal levels of total antibiotic use and disaggregated by AWaRe group in DID for a 2019 baseline for 186 CTAs and compares actual levels of AWaRe use to expected optimal use for 67 CTAs using the IQVIA MIDAS(R) dataset. We used publicly available data from the Global Burden of Disease (GBD), Global Research on Antimicrobial Resistance (GRAM) and the World Bank to provide an open-access, standardised AWaRe-clinical framework that could inform national and global evidence-based antibiotic policy development and implementation. Implications of all the available evidenceAlthough some recent studies have attempted to derive estimates for optimal levels of antibiotic use, they have been focused on specific infections or antibiotics. The UNGA AMR commitments provide a clear direction for global target setting for antibiotic use. Our study provides the first method to estimate optimal antibiotic levels at a country level for both total and AWaRe, based on local infection burden and antibiotic resistance for 186 CTAs. Estimating optimal antibiotic levels with an agreed standard methodology across CTAs would allow for benchmarking and peer-comparison, assisting with target setting and shared learning across National Action Plans from different policy initiatives and outcomes.