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Microbial pollution of surface waters poses substantial risks for public health, amongst others during recreational use. Microbial pollution was studied at selected sampling sites in rivers Rhine, Moselle and Lahn (Germany) on the basis of commonly used fecal indicator organisms (FIO) indicating bacterial (Escherichia coli, intestinal enterococci) and viral (somatic coliphages) fecal contamination. In addition, blaCTX-Mantibiotic resistance genes (ARG) were quantified at twosites in river Lahn and were used as markers for tracking the spread of antibiotic resistance in the aquatic environment. The impact of changes in climate-related parameters on FIO was examined by studying monitoring results of contrasting flow conditions at rivers Rhine and Moselle. Analyses at all studied river sites clearly indicate that high discharge and precipitation enhance the influx of FIO, ARG and thus potentially (antibiotic resistant) pathogens into rivers. In contrast, a decrease in hygienic microbial pollution was observed under high solar irradiation and increasing water temperatures. Based on identified contributing key factors, multiple linear regression (MLR) models for five sites at a stretch of river Lahn were established that allow a timely assessment of fecal indicator abundances. An interaction between abiotic and biotic factors (i.e. enhanced grazing pressure) considerably contributed to the formation of seasonal patterns among FIO abundances. This was enhanced during extraordinary low flow conditions in rivers with pronounced trophic interactions, clearly hampering a transfer of model approaches between rivers of different biological and hydrological characteristics. Bacterial indicatorswere stronger influenced by grazing pressure than phages. Hence, bacterial indicators alone do not sufficiently describe viral pollution in rivers. BlaCTX-Mgenes were omnipresent in Lahn River water and corresponded to distribution patterns of FIO, indicating fecal sources. Agriculture and waste watertreatment plant effluents contributed to ARG loads and participants in non-bathing water sports were found to be at risk of ingesting antibiotic resistant bacteria (ARB) including ARG, bearing the risk of infection or colonization. Results of the present study highlight the need to be aware of such risks not only in designated bathing waters. ARG abundance at both riverine sampling sites could largely be explained by E. coliabundance and may thus also be incorporated into multiple regression models using E. colispecific environmental predictors. It can be expected that the frequency of short-term microbial pollution events will increase over the next decades due to climate change. Several challenges were identified with regard to the implementation of early warning systems to protect the public from exposure to pathogens in rivers. Most importantly, the concept of the Bathing Water Directive (Directive 2006/7/EC) itself as well as the lack of harmonization in the regulatory framework at European Union (EU) level are major drawbacks and require future adjustments to reliably manage health risks related to microbial water pollution in waters used in multifunctional ways.