BACKGROUNDAzithromycin (AZM), a 15-member macrolide antibiotic, has caused widespread pollution in China, where anaerobic digestion is the predominant wastewater treatment technology. However, the type of anaerobic sludge most suitable for treating antibiotic wastewater is unclear. Therefore, this study aimed to determine the response of anaerobic flocculent and granular sludge to AZM wastewater, and, using a high-throughput sequencing technique, to explain the diverse microbial community structures. RESULTSAnaerobic granular sludge provided better resistance to the decline of chemical oxygen demand (COD) removal caused by AZM and greater biodegradation efficiency than flocculent sludge. Furthermore, there was stronger resistance to AZM-induced reactive oxygen species in the granular sludge than in the flocculent sludge. The granular sludge exhibited richer microbial communities than the flocculent sludge after AZM exposure to the phylum Proteobacteria and Bacteroidetes. CONCLUSIONAt high AZM concentration, anaerobic granular sludge was superior to flocculent sludge in COD removal and AZM degradation. This is attributed to less cell death and greater microbial diversity and richness in the granular sludge than in the flocculent sludge following exposure to AZM. Proteobacteria and Bacteroidetes contributed to the resistance to AZM in the granular sludge. (c) 2018 Society of Chemical Industry