Occurrence, distribution, and behaviors of erythromycin A, production byproducts, transformation products, and resistance genes in a full-scale erythromycin A production wastewater treatment system

Abstract

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.