Antibiotic production wastewater from pharmaceutical manufacturing is a significant source of antibiotic and resistance gene pollution in the environment. Given that Erythromycin A (Ery-A) is a widely used antibiotic in both human clinical and livestock breeding, it is imperative to ascertain its presence, along with related compounds, in the biological treatment processes of production wastewater. In this study, the occurrence and behavior of Ery-A, its production byproducts, transformation products, and resistance genes were first systematically investigated in a full-scale anaerobic-aerobic system for treating Ery-A production wastewater. Simultaneously, residual antibacterial activity in wastewater and sludge was evaluated throughout the wastewater treatment process. Ery-A contributes only 24.2 – 36.0% to the antibacterial activities. Ery-A-derived compounds including production byproducts (erythromycin B and erythromycin C) and transformation products (anhydro erythromycin A, N-demethyl-erythromycin A, and erythromycin A enol ether), are determined to contribute to the antibacterial activities of the wastewater treatment system. High concentrations of antibiotics with antibacterial activity (up to 1,258.9 mg/kg·TS for erythromycin A enol ether) adsorbed in the sludge result in near collapse of the first-stage anaerobic sludge system. Sludge biodegradation in second-stage anaerobic and anoxic-aerobic tanks is essential in removing Ery-A-related compounds from wastewater. The Ery-A-related compounds in the secondary effluent and excess sludge are determined to be 44.5 g/h and 1.5 g/h through the mass balance analysis, respectively. The discharge of MLS resistance genes from the secondary effluent and excess sludge is 1.0 × 10¹⁶ copies/h and 7.1 × 10¹⁵ copies/h, respectively. These findings highlight the significant concern over the release of Ery-A-related compounds and MLS resistance genes from the Ery-A production wastewater treatment system. As a result, it is crucial to implement strategies for the removal of Ery-A-related compounds from production wastewater before biological processes. This study is the first to report the occurrence and behavior of Ery-A-related compounds and resistance genes along the full-scale wastewater treatment processes. Additionally, it sheds light on the importance of byproducts and transformation products with antibacterial activity from Ery-A in the Ery-A production wastewater treatment system.

药品生产中的抗生素生产废水是环境中抗生素和耐药基因污染的重要来源。鉴于红霉素 A (Ery-A) 是一种在人类临床和畜牧养殖中广泛使用的抗生素，因此必须确定其在生产废水生物处理过程中以及相关化合物的存在。在这项研究中，首先在处理 Ery-A 生产废水的全规模厌氧-好氧系统中系统地研究了 Ery-A 及其生产副产物、转化产物和抗性基因的发生和行为。同时，在整个废水处理过程中对废水和污泥中的残留抗菌活性进行了评估。Ery-A 的抗菌活性仅贡献 24.2 – 36.0%。Ery-A 衍生化合物，包括生产副产物（红霉素 B 和红霉素 C）和转化产物（脱水红霉素 A、N-去甲基红霉素 A 和红霉素 A 烯醇醚），被确定有助于废水处理的抗菌活性系统。污泥中吸附的高浓度具有抗菌活性的抗生素（红霉素A烯醇醚高达1,258.9 mg/kg·TS）导致一级厌氧污泥系统几近崩溃。第二阶段厌氧和缺氧-好氧池中的污泥生物降解对于去除废水中的 Ery-A 相关化合物至关重要。通过质量平衡分析确定二级出水和剩余污泥中的Ery-A相关化合物分别为44.5 g/h和1.5 g/h。二级出水和剩余污泥中MLS抗性基因的排放量分别为1.0×10 ¹⁶拷贝/小时和7.1×10¹⁵拷贝/小时。这些发现凸显了人们对 Ery-A 生产废水处理系统中 Ery-A 相关化合物和 MLS 抗性基因释放的严重担忧。因此，在生物过程之前实施从生产废水中去除 Ery-A 相关化合物的策略至关重要。这项研究首次报告了 Ery-A 相关化合物和抗性基因在全面废水处理过程中的出现和行为。此外，它还揭示了 Ery-A 生产废水处理系统中 Ery-A 副产物和具有抗菌活性的转化产物的重要性。