Conrad Marx

Occurrence and removal of frequently prescribed pharmaceuticals and corresponding metabolites in wastewater of a sewage treatment plant.

The present study determines removal rates (RR) of 56 pharmaceuticals and metabolites, respectively, in an urban sewage treatment plant using mass flow analysis by comparing influent and effluent loads over a consecutive ten-day monitoring period. Besides well investigated compounds like carbamazepine and metoprolol, less researched targets, such as topiramate, pregabalin, telmisartan, and human metabolites of pharmaceuticals were included. Another aim was to determine the ratio of pharmaceuticals and corresponding metabolites in raw wastewater. Valsartan and gabapentin were detected at the highest average concentrations in influent (c(val) = 29.7 (± 8.1) μg/L, c(gab) = 13.2 (± 3.3) μg/L) and effluent (c(val) = 22.1 (± 5.1) μg/L, c(gab) = 12.1 (± 2.6) μg/L) samples. The comparison of mass loads in influent and effluent showed a significant removal (p<0.1) for 20 compounds but only enalapril, eprosartan, losartan, pregabalin, and quetiapine were removed from the aqueous phase by more than 50%. Another 20 compounds were determined without significant difference and for five compounds (clindamycin, lamotrigine, oxcarbazepine, O-desmethyl venlafaxine, triamterene), a significant higher mass load in the effluent than in the influent was observed. It has to be noticed that metabolites like 10,11-dihydro-10-hydroxy carbamazepine (MHD) are found in higher mass loads than the corresponding parent compound in the sewage samples. Furthermore, metabolites and parent compound behave differently in the sewage treatment process. While MHD (RR = 15.1%) was detected with lower mass load in the effluent than in the influent, oxcarbazepine (RR = -73.2%) showed the contrary pattern. When comparing expected and measured ratios of parent compound and metabolite in raw sewage, citalopram/N-desmethyl citalopram for example, showed good results. However, a major problem exists due to insufficient data regarding metabolism and excretion of many pharmaceuticals. This complicates the prediction of relevant metabolites and further efforts are needed to overcome this problem.

Mass flow of antibiotics in a wastewater treatment plant focusing on removal variations due to operational parameters.

Wastewater treatment plants (WWTPs) are not designed to purposefully eliminate antibiotics and therefore many previous investigations have been carried out to assess their fate in biological wastewater treatment processes. In order to consolidate previous findings regarding influencing factors like the solid and hydraulic retention time an intensive monitoring was carried out in a municipal WWTP in Germany. Over a period of 12months daily samples were taken from the in- and effluent as well as diverse sludge streams. The 14 selected antibiotics and one metabolite cover the following classes: cephalosporins, diaminopyrimidines, fluoroquinolones, lincosamide, macrolides, penicillins, sulfonamides and tetracyclines. Out of the 15 investigated substances, the removal of only clindamycin and ciprofloxacin show significant correlations to SRT, temperature, HRT and nitrogen removal. The dependency of clindamycins removal could be related to the significant negative removal (i.e. production) of clindamycin in the treatment process and was corrected using the human metabolite clindamycin-sulfoxide. The average elimination was adjusted from -225% to 3% which suggests that clindamycin can be considered as an inert substance during the wastewater treatment process. Based on the presented data, the mass flow analysis revealed that macrolides, clindamycin/clindamycin-sulfoxide and trimethoprim were mainly released with the effluent, while penicillins, cephalosporins as well as sulfamethoxazole were partly degraded in the studied WWTP. Furthermore, levofloxacin and ciprofloxacin are the only antibiotics under investigation with a significant mass fraction bound to primary, excess and digested sludge. Nevertheless, the sludge concentrations are highly inconsistent which leads to questionable results. It remains unclear whether the inconsistencies are due to insufficiencies in sampling and/or analytical determination or if the fluctuations can be considered reasonable for digesters. Hence, future investigations have to address antibiotics temporal dynamics during the sludge treatment to decide whether or not the widely reported standard deviations of sludge concentrations reflect realistic fluctuations.

Environmental risk assessment of antibiotics including synergistic and antagonistic combination effects.

The interaction-based hazard index (HIint) allows a prediction of mixture effects different from linear additivity by including information on binary mixtures between the chemicals. The aim of this study is to make a solid estimate on the possible synergistic potential of combined antibiotics and to quantify the subsequent effect for the case of the receiving river Elbe, Germany. Pieces of information on binary interactions between antibiotic groups were used from literature and from knowledge on human antibiotic combination therapy. Applying a moderate and a worst-case scenario, in terms of the interaction magnitude, resulted in 50 to 200% higher environmental risks, compared to the classical assessment approach applying simple concentration addition. A subsequent sensitivity analysis revealed that the data strength for some binary antibiotic combinations is too low to be considered for a solid estimate of synergistic effects. This led to the definition of certain preconditions in order to decide whether or not to include certain interaction information (e.g. the necessary number of interaction studies). The exclusion of information with low data strength resulted in an attenuated risk increase of 20 to 50%, based on the currently available scientific information on binary antibiotic mixtures. In order to include antibiotics with the highest share in the overall risk (macrolides, quinolones, and cephalosporins) as well as their corresponding metabolites, investigations should focus on binary interactions between them.

Representative input load of antibiotics to WWTPs: Predictive accuracy and determination of a required sampling quantity.

Predicting the input loads of antibiotics to wastewater treatment plants (WWTP) using certain input data (e.g. prescriptions) is a reasonable method if no analytical data is available. Besides the spatiotemporal uncertainties of the projection itself, only a few studies exist to confirm the suitability of required excretion data from literature. Prescription data with a comparatively high resolution and a sampling campaign covering 15 months were used to answer the question of applicability of the prediction approach. As a result, macrolides, sulfamethoxazole and trimethoprim were almost fully recovered close to 100% of the expected input loads. Nearly all substances of the beta-lactam family exhibit high elimination rates during the wastewater transport in the sewer system with a low recovery rate at the WWTP. The measured input loads of cefuroxime, ciprofloxacin and levofloxacin fluctuated greatly through the year which was not obvious from relatively constant prescribed amounts. The latter substances are an example that available data are not per se sufficient to monitor the actual release into the environment. Furthermore, the extensive data pool of this study was used to calculate the necessary number of samples to determine a representative annual mean load to the WWTP. For antibiotics with low seasonality and low input scattering a minimum of about 10 samples is required. In the case of antibiotics exhibiting fluctuating input loads 30 to 40 evenly distributed samples are necessary for a representative input determination. As a high level estimate, a minimum number of 20-40 samples per year is proposed to reasonably estimate a representative annual input load of antibiotics and other micropollutants.

Determination of clindamycin and its metabolite clindamycin sulfoxide in diverse sewage samples

In a research project on risk management of harmful substances in water cycles, clindamycin and 12 further antibiotics were determined in different sewage samples. In contrast to other antibiotics, an increase of the clindamycin concentration in the final effluent in comparison to the influent of the sewage treatment plant (STP) was observed. A back transformation from the main metabolite clindamycin sulfoxide to clindamycin during the denitrification process has been discussed. Therefore, the concentration of this metabolite was measured additionally. Clindamycin sulfoxide was stable in the STP and the assumption of back transformation of the metabolite to clindamycin was confuted. To explain the increasing clindamycin concentration in the STP, the ratio of clindamycin sulfoxide to clindamycin was observed. The ratio increased in dry spells with concentrated samples and with long dwell time in the sewer system. A short hydraulic retention in waste water system and diluted samples in periods of extreme rainfall lead to a lower ratio of clindamycin sulfoxide to clindamycin concentration. A plausible explanation of this behavior could be that clindamycin was adsorbed strongly to a component of the sewage during this long residence time and in the STP, clindamycin was released. In the common sample preparation in the lab, clindamycin was not released. Measurements of clindamycin and clindamycin sulfoxide in the influent and effluent of STP is advised for sewage monitoring.

Species-related risk assessment of antibiotics using the probability distribution of long-term toxicity data as weighting function: a case study

Urban areas are among the main sources which release antibiotics into the environment. The fate of antibiotics during their passage through the human body, the sewer system and the waste water treatment processes can be estimated and used for ecological risk assessment. The present approach deals with the possibility of addressing the ecological impact on individual trophic levels using a probability function to attenuate the classical PNEC approach. The species sensitivity distribution (SSD) is based on available long-term toxicity data and was fitted using the Hill-equation. The species-related toxicity threshold was merged with the slope characteristics gathered from SSD to express the risk probability of each species level. The results for algae and crustaceans show that azithromycin, clarithromycin and ciprofloxacin contribute the highest risk portions to the risk index (RI). The determined RI for fish was found to be below the threshold value of 1 and thus no risk is expected for this species.

Emissionsdynamik urbaner Antibiotikaeinträge unter Verwendung von Verschreibungs- und Felddaten

ZusammenfassungHintergrund und FragestellungAntibiotika gelangen über das Abwassersystem in die Abwasserreinigungsanlage und verlassen diese auch teilweise unverändert nach den dort stattfindenden Reinigungsprozessen. Die biologisch aktiven Substanzen gelangen in das sich anschließende Fließgewässer und können die darin lebenden Organismen negativ beeinflussen. Es ist daher erforderlich, den Eintrag, Transport und Verbleib sowie die Effekte der Antibiotika zu charakterisieren, um Maßnahmen zur Schadensminimierung zu identifizieren und effizient einzusetzen.Material und MethodenFür die Auswertung standen die wöchentlich erfassten Verschreibungsdaten der AOK PLUS (2005–2011) zur Verfügung, welche auf das Einzugsgebiet der betreffenden Kläranlage Dresden-Kaditz extrapoliert wurden. Die Abgabemenge der Krankenhausapotheken der drei größten Dresdner Krankenhäuser ergänzten die Abschätzung des Antibiotika-Eintrags. Die Verifizierung der extrapolierten Eintragsdaten erfolgte auf Basis der Analyse der Antibiotikakonzentrationen im Zulauf der Kläranlage. Das Messprogramm umfasste tägliche 24h-Mischproben von Oktober 2012 bis Oktober 2013.Ergebnisse und DiskussionDie Auswertung der Messdaten ergab erwartungsgemäß eine geringe Wiederfindungsrate für die Beta-Laktam-Antibiotika. Dem gegenüber war es möglich, einen guten Abgleich zwischen den verschriebenen Mengen anderer Antibiotikagruppen und den korrespondierenden Frachten im Kläranlagenzulauf herzustellen. Hierzu zählen unter anderem die Makrolide Roxithromycin, Clarithromycin und Azithromycin, welche zusätzlich eine ausgeprägte saisonale Komponente aufweisen. Inwieweit die Abschätzung von stark adsorbierenden Substanzen wie den Fluorchinolonen und Tetracyclinen verbessert werden kann, ist zu prüfen. Nach bisherigem Kenntnisstand führt deren starke Affinität zu Feststoffen zu einer Verzögerung des Transportes in der Kanalisation, die aufgrund der Komplexität des Ableitungssystems nur schwer verifizierbar ist.AbstractBackground and objectiveThe consumption of antibiotics by humans leads to their excretion with no or partial elimination of the biologically active compounds. Furthermore, a multitude of antimicrobial substances are not being eliminated by conventional waste water treatment and ultimately discharged into the receiving waters. Antibiotics, even at low concentrations, are potent stressors to aquatic organisms and trigger a negative impact on the ecosystem. Hence, a better understanding of input, transport and transformation processes is needed for applying an adequate risk assessment and management of these substances.Material and methodsPrescription data provided by the statutory health insurance company AOK PLUS were extrapolated to estimate antibiotic inputs in the catchment area of the sewage treatment plant Dresden-Kaditz. Additional data from three major hospitals support and refine the input prognosis. In order to confirm the employed assumptions used for the input estimation a measuring program was established which covered the period from October 2012 to October 2013. 24h-mixed composite samples were taken daily and analyzed for a variety of antimicrobial substances.Results and discussionAs expected, antibiotics of the beta-lactamases group show poor recovery rates at the inflow of the wastewater treatment plant. In turn, determined input loads of some persistent antibiotics correspond well with the estimated amount of the prognosis method. The seasonal variation of the macrolides Roxithromycin, Clarithromycin and Azithromycin was also well recovered and underlines the estimation robustness. It needs to be established whether the prognosis can be extended to substances with high adsorption affinity to particulate matter. Antibiotics like fluorquinolones and tetracyclines show delayed transport behavior in sewer systems due to their accumulation on to the sewer sediment. These processes are highly complex and hard to verify.

Antibiotikaeintrag in das urbane Abwasser

Antibiotics are essential for the successful treatment of bacterial infections. Recently, the increasing number of resistant bacteria and the occurrence of residues of antibiotics in the environment has become the focus of scientific interest. The aim of the cooperative project ANTI-Resist was to investigate the release of antibiotics and the occurrence and distribution of antibiotic resistance in the urban waste water system of the city of Dresden.This article presents the main results of the secondary data analysis for the determination of outpatient and inpatient antibiotic consumption and provides an insight into the complexity of the topic antibiotics in waste water.Based on the data of outpatient prescriptions provided by the AOK PLUS for the period 2005 to 2013, thirteen focus substances were identified to estimate antibiotic consumption. Furthermore, delivery data from the pharmacies of three hospitals in Dresden were available.Depending on the substances investigated, seasonality and age dependency were determined. The results at a regional level were mostly in good accordance with general trends throughout Germany. It should be noted that the total amount of antibiotics used remained nearly constant over the whole period investigated, but the prescription of fluoroquinolones increased. This must be questioned when taking into account the increasingly critical situation in the treatment of Gram-negative bacteria in particular. Examinations of waste water conducted indicated that sewage treatment plants are not able to remove antibiotics or their metabolites completely from waste water. The residues are released into surface waters via the treatment plants. The impact cannot be assessed at the moment and further investigations are necessary.ZusammenfassungAntibiotika sind zur erfolgreichen Behandlung bakterieller Infektionen unerlässlich. Zuletzt sind jedoch die zunehmende Resistenzproblematik und die Auswirkungen von Antibiotikarückständen in der Umwelt in den wissenschaftlichen Fokus gerückt. Ziel des hier vorgestellten ANTI-Resist-Verbundprojekts war die Untersuchung von Antibiotikaeinträgen und die Analyse der Bildung und Verbreitung von Antibiotikaresistenzen im urbanen Abwassersystem der Stadt Dresden. Der vorliegende Beitrag stellt zentrale Ergebnisse der Sekundärdatenanalyse zur Ermittlung des ambulanten und stationären Antibiotikaverbrauchs vor und gibt einen Einblick in die Komplexität der Thematik Antibiotika im Abwasser. Auf Basis der ambulanten Verschreibungsdaten der AOK PLUS für den Zeitraum 2005 bis 2013 wurden 13 Fokussubstanzen identifiziert, um den Antibiotikaverbrauch abzuschätzen. Außerdem standen Lieferdaten von Krankenhausapotheken dreier Krankenhäuser in Dresden zur Verfügung. Je nach den betrachteten Substanzen konnten Saisonalitäten und Altersabhängigkeiten festgestellt werden. Die Ergebnisse auf regionaler Ebene decken sich überwiegend mit bundesweiten Trends. Dabei ist festzustellen, dass der Antibiotikaeinsatz insgesamt über den betrachten Zeitraum hinweg konstant bleibt, die Verschreibung von Fluorchinolonen jedoch zunimmt. Vor dem Hintergrund der vor allem im gram-negativen Bereich zunehmenden Resistenzsituation sind diese Befunde besonders kritisch zu hinterfragen. Durchgeführte Abwasseranalysen konnten zeigen, dass Kläranlagen nicht dazu geeignet sind, Antibiotika und deren Metabolite vollständig aus dem Abwasser zu entfernen. Über die Kläranlage gelangen die Rückstände in Oberflächengewässer. Die genauen Auswirkungen sind derzeit noch nicht absehbar und müssen weiter untersucht werden.AbstractAntibiotics are essential for the successful treatment of bacterial infections. Recently, the increasing number of resistant bacteria and the occurrence of residues of antibiotics in the environment has become the focus of scientific interest. The aim of the cooperative project ANTI-Resist was to investigate the release of antibiotics and the occurrence and distribution of antibiotic resistance in the urban waste water system of the city of Dresden.This article presents the main results of the secondary data analysis for the determination of outpatient and inpatient antibiotic consumption and provides an insight into the complexity of the topic antibiotics in waste water.Based on the data of outpatient prescriptions provided by the AOK PLUS for the period 2005 to 2013, thirteen focus substances were identified to estimate antibiotic consumption. Furthermore, delivery data from the pharmacies of three hospitals in Dresden were available.Depending on the substances investigated, seasonality and age dependency were determined. The results at a regional level were mostly in good accordance with general trends throughout Germany. It should be noted that the total amount of antibiotics used remained nearly constant over the whole period investigated, but the prescription of fluoroquinolones increased. This must be questioned when taking into account the increasingly critical situation in the treatment of Gram-negative bacteria in particular. Examinations of waste water conducted indicated that sewage treatment plants are not able to remove antibiotics or their metabolites completely from waste water. The residues are released into surface waters via the treatment plants. The impact cannot be assessed at the moment and further investigations are necessary.

A black-box model for generation of site-specific WWTP influent quality data based on plant routine data

This paper presents a simple method for the generation of continuous influent quality datasets for wastewater treatment plants (WWTPs) that is based on incomplete available routine data, only, without referring to any further measurement. In the approach, Weibull-distributed random data are fitted to the available routine data, such that the resulting distribution of influent quality data shows the identical statistical characteristics. Beside the description of the method, this paper contains a comprehensive analysis of robustness and universality of the approach. It is shown that incomplete datasets with only 10% remaining influent quality data can be filled with this method with nearly the same statistical parameters as the original data. In addition, the use with datasets of different WWTP plants sizes results always in a good agreement between original and filled datasets.

Antibiotikaeintrag in das urbane Abwasser@@@Release of antibiotics into urban wastewater: Eine sekundärdatenbasierte Analyse zur Eintragsabschätzung am Beispiel der Stadt Dresden@@@A secondary-data based analysis for the input assessment using the city of Dresden as an example

Antibiotics are essential for the successful treatment of bacterial infections. Recently, the increasing number of resistant bacteria and the occurrence of residues of antibiotics in the environment has become the focus of scientific interest. The aim of the cooperative project ANTI-Resist was to investigate the release of antibiotics and the occurrence and distribution of antibiotic resistance in the urban waste water system of the city of Dresden.This article presents the main results of the secondary data analysis for the determination of outpatient and inpatient antibiotic consumption and provides an insight into the complexity of the topic antibiotics in waste water.Based on the data of outpatient prescriptions provided by the AOK PLUS for the period 2005 to 2013, thirteen focus substances were identified to estimate antibiotic consumption. Furthermore, delivery data from the pharmacies of three hospitals in Dresden were available.Depending on the substances investigated, seasonality and age dependency were determined. The results at a regional level were mostly in good accordance with general trends throughout Germany. It should be noted that the total amount of antibiotics used remained nearly constant over the whole period investigated, but the prescription of fluoroquinolones increased. This must be questioned when taking into account the increasingly critical situation in the treatment of Gram-negative bacteria in particular. Examinations of waste water conducted indicated that sewage treatment plants are not able to remove antibiotics or their metabolites completely from waste water. The residues are released into surface waters via the treatment plants. The impact cannot be assessed at the moment and further investigations are necessary.ZusammenfassungAntibiotika sind zur erfolgreichen Behandlung bakterieller Infektionen unerlässlich. Zuletzt sind jedoch die zunehmende Resistenzproblematik und die Auswirkungen von Antibiotikarückständen in der Umwelt in den wissenschaftlichen Fokus gerückt. Ziel des hier vorgestellten ANTI-Resist-Verbundprojekts war die Untersuchung von Antibiotikaeinträgen und die Analyse der Bildung und Verbreitung von Antibiotikaresistenzen im urbanen Abwassersystem der Stadt Dresden. Der vorliegende Beitrag stellt zentrale Ergebnisse der Sekundärdatenanalyse zur Ermittlung des ambulanten und stationären Antibiotikaverbrauchs vor und gibt einen Einblick in die Komplexität der Thematik Antibiotika im Abwasser. Auf Basis der ambulanten Verschreibungsdaten der AOK PLUS für den Zeitraum 2005 bis 2013 wurden 13 Fokussubstanzen identifiziert, um den Antibiotikaverbrauch abzuschätzen. Außerdem standen Lieferdaten von Krankenhausapotheken dreier Krankenhäuser in Dresden zur Verfügung. Je nach den betrachteten Substanzen konnten Saisonalitäten und Altersabhängigkeiten festgestellt werden. Die Ergebnisse auf regionaler Ebene decken sich überwiegend mit bundesweiten Trends. Dabei ist festzustellen, dass der Antibiotikaeinsatz insgesamt über den betrachten Zeitraum hinweg konstant bleibt, die Verschreibung von Fluorchinolonen jedoch zunimmt. Vor dem Hintergrund der vor allem im gram-negativen Bereich zunehmenden Resistenzsituation sind diese Befunde besonders kritisch zu hinterfragen. Durchgeführte Abwasseranalysen konnten zeigen, dass Kläranlagen nicht dazu geeignet sind, Antibiotika und deren Metabolite vollständig aus dem Abwasser zu entfernen. Über die Kläranlage gelangen die Rückstände in Oberflächengewässer. Die genauen Auswirkungen sind derzeit noch nicht absehbar und müssen weiter untersucht werden.AbstractAntibiotics are essential for the successful treatment of bacterial infections. Recently, the increasing number of resistant bacteria and the occurrence of residues of antibiotics in the environment has become the focus of scientific interest. The aim of the cooperative project ANTI-Resist was to investigate the release of antibiotics and the occurrence and distribution of antibiotic resistance in the urban waste water system of the city of Dresden.This article presents the main results of the secondary data analysis for the determination of outpatient and inpatient antibiotic consumption and provides an insight into the complexity of the topic antibiotics in waste water.Based on the data of outpatient prescriptions provided by the AOK PLUS for the period 2005 to 2013, thirteen focus substances were identified to estimate antibiotic consumption. Furthermore, delivery data from the pharmacies of three hospitals in Dresden were available.Depending on the substances investigated, seasonality and age dependency were determined. The results at a regional level were mostly in good accordance with general trends throughout Germany. It should be noted that the total amount of antibiotics used remained nearly constant over the whole period investigated, but the prescription of fluoroquinolones increased. This must be questioned when taking into account the increasingly critical situation in the treatment of Gram-negative bacteria in particular. Examinations of waste water conducted indicated that sewage treatment plants are not able to remove antibiotics or their metabolites completely from waste water. The residues are released into surface waters via the treatment plants. The impact cannot be assessed at the moment and further investigations are necessary.