Persistence, ecotoxicity, and emerging remediation strategies for doxycycline: A critical review

Doxycycline is a second-generation tetracycline antibiotic, commonly used in human and veterinary medicine. The present study critically reviews the prevalence and toxicity of doxycycline in various environmental matrices and their removal strategies. Doxycycline is established to persist in aquatic and soil environments at levels reaching up to 30.9 μg/L and 78,516 μg/kg (dry weight), respectively. The prevalence typically falls in the range of minimum selective concentrations, usually below minimum inhibitory concentrations (MIC) and falls within the mutant selection window (MSW), affecting antimicrobial resistance (AMR) in bacteria. Doxycycline residues and transformation products such as 4-epi-doxycycline (EDC) also perturb aquatic ecological homeostasis with their sub-lethal toxicity, facilitating antimicrobial gene proliferation. Hence, the development of technologies for the complete removal of doxycycline is an immediate concern to mitigate AMR. Conventional technologies such as coagulation, biological methods and advanced effluent treatment processes, which include adsorption, ion exchange, electrochemical methods, and advanced oxidation processes, were studied extensively for the removal of doxycycline. However, they face challenges, including energy demand, transformation product toxicity, and scale-up. It was inferred that hybrid and integrated treatment methods, which synergistically combine various degradation mechanisms such as adsorption - heterogeneous Fenton-like oxidation processes and bioelectrodegradation, exhibited enhanced removal efficiency. Critical challenges, perspectives and prospects for regulators and scientists are proposed. This review also highlights key aspects for the development and deployment of cost-effective, sustainable, scalable and high-throughput technologies for the removal of doxycycline.