Environmental fate of pharmaceutical compounds and antimicrobial-resistant bacteria in hospital effluents, and contributions to pollutant loads in the surface waters in Japan.

Environmental fate of 58 pharmaceutical compounds (PhCs) grouped into 11 therapeutic classes in the three different waters, hospital effluent, sewage treatment plant (STP) and river water, was estimated by combination of their quantitative concentration analysis and evaluation of their extent of contribution as loading sources. At the same time, distribution of six classes of antimicrobial-resistant bacteria (AMRB) in the same water samples was estimated by screening of individual PhC-resistant microbes grown on each specific chromogenic medium. The results indicate that 48 PhCs were detected ranged from 1 ng/L (losartan carboxylic acid) to 228 µg/L (acetaminophen sulfate) in hospital effluent, and contribution of the pollution load derived from hospital effluent to STP influent was estimated as 0.1% to 15%. On the other hand, contribution of STP effluent to river water was high, 32% to 60% for antibacterials, antipertensives and X-ray contrast media. In the cases for AMRB, detected numbers of colonies of AMRB in hospital effluent ranged from 29 CFU/mL to 1805 CFU/mL, and the estimated contribution of the AMRB pollution load derived from hospital effluent to STP influent was as low as 0.1% (levofloxacin and olmesartan) to 5.1% (N-desmethyl tamoxifen). Although the contribution of STPs as loading sources of PhCs and AMRB in surface waters was large, ozonation as an advanced water treatment system effectively removed a wide range of both PhCs and AMRB in water samples. These results suggest the importance of reducing environmental pollutant loads (not only at STPs but also at medical facilities) before being discharged into the surface waters, to both conserve water and keep the water environment safe. To our knowledge, this is the first report to show the distribution and contribution of AMRB from hospital effluent to the surface waters.

Performance and efficiency of removal of pharmaceutical compounds from hospital wastewater by lab-scale biological treatment system.

The fate of pharmaceuticals after discharged from hospital into wastewater was clarified experimentally by using a new lab-scale conventional activated sludge (CAS) treatment reactor. The 43 target compounds belong to nine therapeutic classes (antivirals, antibacterials, anticancer drugs, psychotropics, antihypertensives, analgesic-antipyretics, contrast media, herbal medicines, and phytoestrogens) were selected with inclusion of 16 newly estimated compounds. The efficiency of the present reactor was estimated by comparing the reaction rate constant of the solid-water partition coefficients (log Kd) between liquid and solid samples and half-life during 48-h experiment obtained by using hospital effluents with those obtained by using STP wastewater. The results that no significant difference in removal efficiency was observed between both water samples (P > 0.05) indicate high reliability of the present lab-scale reactor. The actual rates of removal when hospital effluent was applied varied widely (mean, 59 ± 40%) independent of type of the pharmaceuticals. More than 90% of 17 compounds were removed after 8 h of treatment. However, the values for psychotropics (mean, 19 ± 26%) and contrast media (mean, 24 ± 17%) were generally low, indicating high stability. The log Kd values ranged from 1.3 to 4.8. Notably, clarithromycin, acridine, and glycitein could be removed in both liquid and solid phases. The dominant removal mechanisms were found to be different for individual pharmaceutical. These results suggest the effectiveness of introduction of the lab-scale biological treatment system for development of a new solution for discharge of pharmaceuticals from hospital.

Fate of new three anti-influenza drugs and one prodrug in the water environment.

We evaluated the environmental fate of new three anti-influenza drugs, favipiravir (FAV), peramivir (PER), and laninamivir (LAN), and an active prodrug of LAN, laninamivir octanoate (LANO), in comparison with four conventional drugs, oseltamivir (OS), oseltamivir carboxylate (OC), amantadine (AMN), and zanamivir (ZAN) by photodegradation, biodegradation, and sorption to river sediments. In addition, we conducted 9-month survey of urban rivers in the Yodo River basin from 2015 to 2016 (including the influenza season) to investigate the current status of occurrence of these drugs in the river environment. The results clearly showed that FAV and LAN rapidly disappeared through photodegradation (half-lives 1 and 8 h, respectively), followed by LANO which gradually disappeared through biodegradation (half-life, 2 days). The remained PER and conventional drugs were, however, persistent and transported from upstream to downstream sites. Rates of their sorption to river sediments were negligibly small. Detected levels remained were in the range from N.D. to 89 ng/L for the river waters and from N.D. to 906 ng/L in sewage effluent. However, all of the remained drugs were effectively removed by ozonation after chlorination at a sewage treatment plant. These findings suggest the importance of introducing ozonation for reduction of pollution loads in rivers, helping to keep river environments safe. To the best of our knowledge, this is the first evaluation of the removal effects of natural sunlight, biodegradation, and sorption to river sediments on FAV, PER, LAN, LANO, and a conventional drug, AMN.

A method for evaluating the pharmaceutical deconjugation potential in river water environments.

A new enzymatic assay method that uses deconjugation enzymes was developed to evaluate the presence and extent of conjugated pharmaceuticals in the form of glucuronide conjugates or sulphate conjugates in river environments. First, acetaminophen glucuronide (Ace Glu) and acetaminophen sulphate (Ace Sul) were used as model conjugated pharmaceuticals to determine the appropriate combination of deconjugation enzymes and reaction conditions, including temperature, duration and pH. Next, we applied the defined method to 19 pharmaceuticals grouped into nine therapeutic classes that were chosen based on previously detected levels and frequencies in sewage and river water. The enzymatic decomposition profile varied widely depending upon the enzyme preparations available. The effect of the water reaction temperature was small between 5 and 40 °C, and the reaction proceeded in for both glucuronide conjugates and sulphate conjugates at an approximately neutral pH (corresponding to usual river water conditions) within 1 h. Application of the method to environmental samples showed that some pharmaceuticals were present in both glucuronide conjugate and sulphate conjugated forms, although glucuronide conjugates were the primary forms in the river water environment. Water treatment systems at sewage treatment plants were found to be effective for the removal of these conjugated compounds. The present results should be valuable in the environmental risk assessment of conjugated pharmaceuticals and in keeping river environments clean. To the best of our knowledge, this is the first report that enables the evaluation of the pharmaceutical deconjugation potential in a river environment.