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Antibiotics, the most frequently prescribed drugs of modern medicine, are extensively used for both human and veterinary applications. Antibiotics from different wastewater sources (e.g., municipal, hospitals, animal production, and pharmaceutical industries) ultimately are discharged into wastewater treatment plants. Sorption and biodegradation are the two major removal pathways of antibiotics during biological wastewater treatment processes. This review provides the fundamental insights into sorption mechanisms and biodegradation pathways of different classes of antibiotics with diverse physical–chemical attributes. Important factors affecting sorption and biodegradation behavior of antibiotics are also highlighted. Furthermore, this review also sheds light on the critical role of extracellular polymeric substances on antibiotics adsorption and their removal in engineered biological wastewater treatment systems. Despite major advancements, engineered biological wastewater treatment systems are only moderately effective (48–77%) in the removal of antibiotics. In this review, we systematically summarize the behavior and removal of different antibiotics in various biological treatment systems with discussion on their removal efficiency, removal mechanisms, critical bioreactor operating conditions affecting antibiotics removal, and recent innovative advancements. Besides, relevant background information including antibiotics classification, physical–chemical properties, and their occurrence in the environment from different sources is also briefly covered. This review aims to advance our understanding of the fate of various classes of antibiotics in engineered biological wastewater treatment systems and outlines future research directions.

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