Occurrence of macrolide antibiotics in drinking water sources and their potential health risks

Macrolide antibiotics (MLAs) are widely utilized in both human and veterinary medicine. Their extensive use has led to ubiquitous contamination in aquatic environments, posing significant risks to public health and ecosystems. Despite their prevalence, comprehensive analyses of their environmental fate, diverse exposure pathways, and potential molecular toxicological mechanisms remain insufficient. This study systematically reviewed MLAs in global drinking water sources from 2005 to 2025 and their potential impacts on health. Using VOSviewer for bibliometric analysis, key research clusters focusing on ecological risks, antimicrobial resistance development, and health outcomes were identified. MLAs are frequently detected in surface and groundwater, with concentrations exceeding 1000 ng/L in specific regions, primarily influenced by seasonal variations and regional industrial activities. Additionally, we assessed how MLAs through the food chain into human dietary sources such as seafood and dairy products. Clinically, MLAs exposure correlates with a range of adverse health outcomes including cardiotoxicity (QT interval prolongation), hearing loss, obesity, and developmental defects. Five representative toxicity pathways were reviewed: mitochondrial dysfunction and impaired mitophagy/apoptosis, hERG potassium channel blockade, altered bile acid homeostasis, nicotinic acetylcholine receptor (nAChR) inhibition, and oxidative stress. The evidence supporting these pathways varies across individual macrolides, and their relevance to exposure through drinking water remains uncertain. By identifying existing research gaps, this review establishes a robust scientific foundation for risk assessment and calls for enhanced oversight to mitigate the environmental and health risks associated with MLAs.