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Antimicrobial activity of pharmaceutical cocktails in sewage treatment plant effluent – An experimental and predictive approach to mixture risk assessment

Journal article
Authors J. Menz
E. Baginska
Åsa Arrhenius
A. Haiß
Thomas Backhaus
K. Kümmerer
Published in Environmental Pollution
Volume 231
Pages 1507-1517
ISSN 0269-7491
Publication year 2017
Published at Department of Biological and Environmental Sciences
Pages 1507-1517
Language en
Keywords Antibiotics, Environmental bacteria, Microbial communities, Mixture toxicity, Aquatic organisms, Effluent treatment, Effluents, Microorganisms, Mixtures, Risk assessment, River pollution, Sewage treatment plants, Toxicity, Active pharmaceutical ingredients, Anti-microbial activity, Community level physiological profiling, Culturable microorganisms, Prokaryotic microorganism, Sewage-treatment plant effluent, Bacteria, acebutolol, carbamazepine, ciprofloxacin, clofibric acid, diclofenac, enoxacin, fenofibrate, gemfibrozil, ibuprofen, lomefloxacin, metoprolol, naproxen, norfloxacin, ofloxacin, oxprenolol, propranolol, sulfamethoxazole, trimethoprim, antimicrobial activity, effluent, experimental study, microbial community, sewage treatment, wastewater treatment plant, Aliivibrio fischeri, aquatic environment, Article, bacterial strain, chemical analysis, concentration (parameters), controlled study, microbial consortium, nonhuman, physiological process, Pseudomonas putida, quantitative analysis, sewage treatment plant, toxicity testing, Europe, Apis, Bacteria (microorganisms), Prokaryota, Vibrio fischeri
Subject categories Environmental Sciences


Municipal wastewater contains multi-component mixtures of active pharmaceutical ingredients (APIs). This could shape microbial communities in sewage treatment plants (STPs) and the effluent-receiving ecosystems. In this paper we assess the risk of antimicrobial effects in STPs and the aquatic environment for a mixture of 18 APIs that was previously detected in the effluent of a European municipal STP. Effects on microbial consortia (collected from a separate STP) were determined using respirometry, enumeration of culturable microorganisms and community-level physiological profiling. The mixture toxicity against selected bacteria was assessed using assays with Pseudomonas putida and Vibrio fischeri. Additional data on the toxicity to environmental bacteria were compiled from literature in order to assess the individual and expected joint bacterial toxicity of the pharmaceuticals in the mixture. The reported effluent concentration of the mixture was 15.4 nmol/l and the lowest experimentally obtained effect concentrations (EC10) were 242 nmol/l for microbial consortia in STPs, 225 nmol/l for P. putida and 73 nmol/l for V. fischeri. The lowest published effect concentrations (EC50) of the individual antibiotics in the mixture range between 15 and 150 nmol/l, whereas 0.9–190 μmol/l was the range of bacterial EC50 values found for the non-antibiotic mixture components. Pharmaceutical cocktails could shape microbial communities at concentrations relevant to STPs and the effluent receiving aquatic environment. The risk of antimicrobial mixture effects was completely dominated by the presence of antibiotics, whereas other pharmaceutical classes contributed only negligibly to the mixture toxicity. The joint bacterial toxicity can be accurately predicted from the individual toxicity of the mixture components, provided that standardized data on representative bacterial strains becomes available for all relevant compounds. These findings argue for a more sophisticated bacterial toxicity assessment of environmentally relevant pharmaceuticals, especially for those with a mode of action that is known to specifically affect prokaryotic microorganisms. Pharmaceutical cocktails pose a risk to microbial communities in sewage treatment plants and the aquatic environment. © 2017 Elsevier Ltd

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