Even without accounting for veterinary or pharmaceutical waste, human antibiotic use alone is pushing rivers past ecological tipping points, putting global water systems and health at risk. Contaminant pathways of antibiotics in the global aquatic environment. Modeled contaminant pathways and mass balances of antibiotics by path. Values in parentheses indicate total amounts of the top 40 antibiotics consumed worldwide in tonnes year−1; percentage values are relative to the total excretion amount (20,500 tonnes year−1). In a recent article published in the journal PNAS Nexus, researchers estimated the quantities of the 40 antibiotics most commonly used by humans that reach oceans and rivers, with a focus on domestic sources. Their analysis underscores the urgent need for global strategies to control pollution. It suggests that 8,500 tons of antibiotics reach river systems each year and that six million kilometers of global rivers exceed safe levels for promoting resistance and harming ecosystem health. Background Antibiotic contamination in natural waters is increasingly reported in sediments, groundwater, and surface water, raising concerns for both human and environmental health. Even at low levels, antibiotics can facilitate the development of resistance genes, reduce microbial diversity, and have a negative impact on aquatic life. Understanding antibiotic pollution is critical because antimicrobial resistance (AMR) is projected to become a leading global health threat. Antibiotics enter the environment due to incomplete human metabolism, insufficient removal in wastewater systems, and widespread use in animal farming, aquaculture, and pharmaceutical manufacturing. Industrial sources are somewhat regulated, but household and hospital wastewater, both important point sources, are often inadequately treated. An estimated half of the wastewater from these sources is released without treatment globally. Since global human antibiotic use has surged, increasing by 65% between 2000 and 2015 and by 114% in low-income countries, concerns about the growing environmental load are intensifying. Advanced treatment technologies exist but are not widely implemented. Moreover, some antibiotic residues may persist in sediments or transform into other biologically active forms. Direct global monitoring of antibiotics is limited by high costs and complexity, making regular tracking difficult. As an alternative, contaminant fate models can simulate the environmental fate of chemicals, helping identify high-risk regions. Environmental exposure levels of antibiotics in global rivers. Total risk quotient (RQtot) is calculated as the sum of individual risk quotients of all 40 antibiotics in the global river system under low-flow conditions. Rivers in gray present insignificant risk (RQtot < 0.01). Only rivers exceeding a long-term average flow of 0.1 m3 s−1 are shown. About the study In this analysis, researchers used a contaminant fate model called HydroFATE to assess whether antibiotics from human use alone pose a threat to river systems globally, based on data from 23.8 million kilometers of river networks. They estimated the antibiotic emissions from human activity by combining population distributions, per capita antibiotic use, and human metabolism rates. The fate of these substances was modeled based on their pathways, including treated and untreated wastewater, as well as natural land attenuation. River networks were simulated to track contaminant transport by calculating how antibiotic loads accumulated downstream, incorporating instream decay and lake removal. Concentrations in rivers were computed as the total load divided by local river discharge. The research team then validated the models by comparing the results with measured antibiotic concentrations at 877 global sites for 21 compounds. The model used the lowest monthly river flow between 1971 and 2000 to simulate risk under plausible but impactful conditions. Environmental exposure was assessed using risk quotients (RQi), calculated as the ratio of modeled concentrations to ecological or resistance-promoting thresholds. These were summed into a total risk quotient (RQtot) to capture cumulative impacts. The exposure faced by humans in terms of health impacts was evaluated using the equivalent dose concentration as a proportion of the defined daily dose and assessed against chronic exposure thresholds. The highest percentile of dose concentrations was used to estimate high-risk human exposure scenarios, assuming untreated water consumption. Annual consumption of the 40 antibiotics selected for inclusion in this study, aggregated by country. Reported values are from Klein et al. (20), and extrapolated values were calculated based on the methodology described in the paper. Findings The researchers estimated that global antibiotic consumption was 32,200 tons per year, with 29,200 tons attributed to the top 40 most commonly used antibiotics. After accounting for additional countries, the estimate rose to 30,300 tons. Of this amount, 68%, or 20,500 tons per year, is excreted, and approximately 29%, or 8,500 tons per year, is estimated to be released into the river system. Only 43% of domestic antibiotic loads are treated through wastewater systems. Centralized plants eliminate 72% of incoming antibiotics but still contribute 17% of emissions. Decentralized and untreated systems contribute 29% and 54%, respectively. Most removal occurs through instream decay (48%) and lake retention (13%). Under conditions of low flow, 49% of the global river length posed no risk, 9% had a low risk, 17% had a medium risk, and 25% had a high to very high risk. About 3.8 million kilometers of rivers had one or more substances that exceeded individual risk thresholds, and 0.7 million kilometers were contaminated by ten or more high-risk antibiotics. Countries like India, Pakistan, and China showed extensive river lengths at high risk, largely driven by common antibiotics such as amoxicillin, ceftriaxone, and cefixime, which were the main contributors by river length exceeding individual high-risk thresholds, although other antibiotics like ciprofloxacin were also significant contributors in specific regions or for human health risk assessment. For human health exposure, 1.4% of global rivers fell within the highest antibiotic dose percentile, potentially affecting over 750 million people under conditions where untreated water was consumed. Conclusions The study finds that human antibiotic use poses significant risks to rivers globally, with even greater risks likely in areas where veterinary use, pharmaceutical waste, and inadequate wastewater treatment are also present. While industrial discharge, aquaculture, and agriculture are key contributors, these were not included in the models due to limitations in data availability. Seasonal peaks and extreme weather events could also lead to higher local concentrations. Despite its constraints, the model reliably estimates long-term risks and highlights the urgent need for improved wastewater management, stricter regulations, and responsible antibiotic use. Policies should prioritize high-risk regions, especially in low- and middle-income countries, and adopt a OneHealth approach in drug approval to protect ecosystems and public health.