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Water Res. 2017 Dec 1;126:79-87. doi: 10.1016/j.watres.2017.09.019. Epub 2017 Sep 9.

Negative environmental impacts of antibiotic-contaminated effluents from pharmaceutical industries.

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Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, Zagreb, Croatia.
Ruđer Bošković Institute, Bijenička 54, Zagreb, Croatia.
Andrija Štampar Teaching Institute of Public Health, Mirogojska cesta 16, Zagreb, Croatia.
Ruđer Bošković Institute, Bijenička 54, Zagreb, Croatia. Electronic address:


Effluents from pharmaceutical industries are recognized as significant contributors to aquatic pollution with antibiotics. Although such pollution has been mostly reported in Asia, knowledge on industrial discharges in other regions of the world, including Europe, and on the effects associated with such exposures is still limited. Thus, we performed chemical, microbiological and ecotoxicological analyses of effluents from two Croatian pharmaceutical industries during four seasons. In treated effluents of the company synthesizing macrolide antibiotic azithromycin (AZI), the total concentration of AZI and two macrolide by-products from its synthesis was 1-3 orders of magnitude higher in winter and springtime (up to 10.5 mg/L) than during the other two seasons (up to 638 μg/L). Accordingly, the highest total concentrations (up to 30 μg/L) in the recipient river were measured in winter and spring. Effluents from second company formulating veterinary antibiotics contained fluoroquinolones, trimethoprim, sulfonamides and tetracyclines ranging from low μg/L to approx. 200 μg/L. Low concentrations of these antibiotics, from below the limit of quantification to approx. few μg/L, have also been measured in the recipient stream. High frequency of culturable bacteria resistant to AZI (up to 83%) or sulfamethazine (up to 90%) and oxytetracycline (up to 50%) were also found in studied effluents. Finally, we demonstrated that toxicity to algae and water fleas often exceeded the permitted values. Most highly contaminated effluents induced multiple abnormalities in zebrafish embryos. In conclusion, using a wide array of analyses we have demonstrated that discharges from pharmaceutical industries can pose a significant ecological and public health concern due to their toxicity to aquatic organisms and risks for promoting development and spread of antibiotic resistance.


Antibiotic pollution; Antibiotic resistance; Drug manufacturing; Ecotoxicity; Macrolides

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