The need for One Health systems-thinking approaches to understand multiscale dissemination of antimicrobial resistance.

Although the effects of antimicrobial resistance (AMR) are most obvious at clinical treatment failure, AMR evolution, transmission, and dispersal happen largely in environmental settings, for example within farms, waterways, livestock, and wildlife. We argue that systems-thinking, One Health approaches are crucial for tackling AMR, by understanding and predicting how anthropogenic activities interact within environmental subsystems, to drive AMR emergence and transmission. Innovative computational methods integrating big data streams (eg, from clinical, agricultural, and environmental monitoring) will accelerate our understanding of AMR, supporting decision making. There are challenges to accessing, integrating, synthesising, and interpreting such complex, multidimensional, heterogeneous datasets, including the lack of specific metrics to quantify anthropogenic AMR. Moreover, data confidentiality, geopolitical and cultural variation, surveillance gaps, and science funding cause biases, uncertainty, and gaps in AMR data and metadata. Combining systems-thinking with modelling will allow exploration, scaling-up, and extrapolation of existing data. This combination will provide vital understanding of the dynamic movement and transmission of AMR within and among environmental subsystems, and its effects across the greater system. Consequently, strategies for slowing down AMR dissemination can be modelled and compared for efficacy and cost-effectiveness.

Multifactorial Evaluation of Atenolol, Caffeine, Carbamazepine and Ibuprofen on Raphidocelis subcapitata and Chlorella vulgaris.

Micropollutants in aquatic resources have raised global concerns regarding the conservation of ecosystems. Although they are usually found in the environment at trace concentrations to a maximum of several µg/L, it is still necessary to address the potential risks these pollutants may represent to organisms. A multifactor analysis was conducted using two algae as bioindicators. Four different pharmaceuticals were chosen based on their occurrence in domestic wastewaters and persistency after biological treatment processes ranging from 1/8th to four-fold representative environmental concentrations over 96 h exposure. The present multifactor analysis evaluated cell size, photosynthetic capacity and growth rate. These data were later combined into a simplified single entity: "the index effect". The results obtained showed that, even at concentrations below the environmentally relevant concentrations (ERC), the pharmaceuticals' residues (PRs), caused a cellular behavioural variation in both organisms. In addition, the algae cultures' response to exposure to these stressors was generally dependent on the concentration over time. By examining four different PR over three different characteristics of two types of algal bioindicators, this work covers significant and specific responses on the algae exposure cycle. This is unique research since most studies do not consider multiple parameters in the assessment of the environment risk for bioindicators.

Effect of eight common Brazilian drugs on Lemna minor and Salvinia auriculata growth.

The growth of two species of macrophytes (Lemna minor and Salvinia auriculata) under the effect of a mixture of amoxicillin, caffeine, carbamazepine, dipyrone, ibuprofen, losartan, omeprazole, and tenivastatin was investigated by bioassay. Three concentration levels were utilized in this study (10, 200, and 500 µg L-1) using a growth inhibition test based on the OECD 221/2006 guidelines. The frond number, total area, and chlorophyll a level were selected as suitable end points. For L. minor, at all concentrations, a significant difference in the total frond number was observed and the growth inhibition varied from 30 to 70% at the low and high concentrations, respectively. No significant growth change was observed to S. auriculata exposed to the mixture of drugs. Thus, individual drug tests were performed for L. minor which demonstrated stimulation in growth, when exposed to most drugs individually, except tenivastatin which was identified as the drug responsible for the significant growth inhibition seen in the mixture. The L. minor enhanced growth was probably caused by N molecule transformation to ammonium and nitrate, essential nutrients for plants.

Pharmaceuticals effect and removal, at environmentally relevant concentrations, from sewage sludge during anaerobic digestion.

This paper investigates the performance of AD in the presence of high-risk pharmaceuticals found in sewage sludge and its removal capacity. The digestion process of synthetic sewage sludge was observed in two 7L glass reactors (D1 and D2) at 38 °C (OLR 1.3 gVS L-1 d-1 and HRT 43 d). Environmentally relevant pharmaceuticals (clarithromycin, clotrimazole, erythromycin, fluoxetine, ibuprofen, sertraline, simvastatin and tamoxifen) were added in D2 at predicted environmental (sludge) conditions. The results demonstrated that long-term presence of pharmaceuticals can affect AD and induce instability resulting in an accumulation of VFAs. This study showed a concurrent effect on AD microbial composition, increasing the percentage of Firmicutes (>70%) and decreasing the percentages of Bacteroidetes and Euryarchaeota (<5%), which seems to be the cause of VFA accumulation and resultant the decrease in the biogas production. However, it seems that anaerobic microorganisms offer enhanced removal of the antibiotics clarithromycin and erythromycin over aerobic techniques.

Oxidative stress responses and cellular energy allocation changes in microalgae following exposure to widely used human antibiotics.

The individual effect of four human antibiotics on the microalgae Raphidocelis subcapitata was investigated following a 120-h exposure. The effects were assessed by analyzing growth, and biochemical parameters related with: 1) antioxidant capacity and oxidative damage by measuring superoxide dismutase (SOD) activity and lipid peroxidation (LPO) levels; and 2) cellular energy allocation (CEA) by quantifying the content in energy reserves, which represents the energy available (Ea), and the electron transport system activity that represents a measure of oxygen and cellular energy consumption (Ec). Growth yield inhibitory concentrations of sulfamethoxazole (18-30%), clarithromycin (28.7%), ciprofloxacin (28%) and erythromycin (17-39%) were found to elicit a considerable increase in Ec, thereby causing a significant decrease in the CEA. The elevated Ec can be a result of the need to respond to oxidative stress occurring under those conditions given the significant increase in SOD activity at these levels. For sulfamethoxazole, erythromycin and ciprofloxacin, the antioxidant responses do not seem to be enough to cope with the reactive oxygen species and prevent oxidative damage, given the elevated LPO levels observed. A stimulatory effect on growth yield was observed (up to 16%) at ciprofloxacin lowest concentration, which highly correlated with the increase in CEA. Based on the no observed effect concentration (NOECs) and/or effective concentration (EC10) results, Ec, SOD and CEA were more sensitive than the classical endpoint of growth rate for all the tested antibiotics. By revealing the antibiotic stress effects in R. subcapitata at the cellular level, this study suggests CEA as a more reliable indicator of the organisms' physiological status.

Identification of the acid-induced degradation products of omeprazole and 5-hydroxyomeprazole by high-resolution mass spectrometry.

RATIONALE: Omeprazole is used to treat gastric disorders and is one of the most commonly consumed drugs in the western world. It forms several metabolites but is mostly excreted unchanged and as 5-hydroxyomeprazole. Since omeprazole is widely prescribed, its excretion from the body has a potential environmental effect. After excretion it will enter the wastewater system and if not adequately removed during wastewater treatment will be discharged into rivers in the wastewater effluent. It is important to consider not only the parent drug, but also the main metabolite (5-hydroxyomeprazole) and their degradation products to fully understand the fate of this drug during wastewater treatment. In order to do this potential degradation products need to be determined. METHODS: Acid was used to artificially accelerate the degradation of omeprazole and 5-hydroxyomeprazole. A Q-Exactive Orbitrap mass spectrometer with an electrospray ionisation source was used to determine precursor and product ion data for the degradation products. RESULTS: Both starting materials quickly degrade under acidic conditions and the main degradation product formed in each case was a re-arranged monomer. Other species identified were doubly and singly charged dimers with varying numbers of sulphur atoms in the dimer bridge. Careful inspection of the accurate mass, isotope pattern, isotope abundance and product ion spectra was used to interpret the data. CONCLUSIONS: The resultant degradants from omeprazole and 5-hydroxyomeprazole were analogous to each other, differing only by an oxygen atom. This investigation determined the degradation products of omeprazole and 5-hydroxyomeprazole and proposed structures based on the accurate mass and isotope information. The product ions from the degradation products are also reported.

Ranking prescribed pharmaceuticals in terms of environmental risk: Inclusion of hospital data and the importance of regular review.

A newly available dataset on pharmaceuticals used in Scottish hospitals enabled an environmental risk assessment that includes hospital consumption of pharmaceuticals, as previous United Kingdom rankings have been based on community prescriptions only. Although health and the environment are devolved issues for the Scottish government, it is merited to consider a Scottish ranking separately; regional differentiation is particularly relevant in the spatial context of the European Commission's Water Framework Directive. Nine pharmaceuticals are identified as having a risk quotient greater than 1. Four of these, the antibacterials piperacillin, tazobactam, flucloxacillin, and ciprofloxacin, had high hospital contributions and had not been highlighted previously in rankings based on community prescriptions. Some drugs with a risk quotient < 0.1 are used almost exclusively in hospitals and could be more concentrated near effluents carrying hospital wastewater, where they may be of local concern. Although treating hospital effluents separately is a policy option, specifically including hospital consumption is important. Continually increasing the availability of ecotoxicological data and trends in consumption further contributes to a substantially different prioritization than in previous rankings. This leads the authors to conclude that regular review of risk is necessary.

Dynamic assessment of the floc morphology, bacterial diversity, and integron content of an activated sludge reactor processing hospital effluent.

The treatment of hospital effluents (HE) is a major concern, as they are suspected of disseminating drugs and antibiotic resistance determinants in the environment. In order to assess HE influence on wastewater treatment plant biomass, lab-scale conventional activated sludge systems (CAS) were continuously fed with real HE or urban effluent as a control. To gain insights into the main hurdles linked to HE treatment, we conducted a multiparameter study using classical physicochemical characterization, phase contrast and confocal laser scaning microscopy, and molecular biology (i.e., pyrosequencing) tools. HE caused erosion of floc structure and the production of extracellular polymeric substances attributed to the development of floc-forming bacteria. Adaptation of the sludge bacterial community to the HE characteristics, thus maintaining the purification performance of the biomass, was observed. Finally, the comparative metagenomic analysis of the CAS showed that HE treatment resulted in an increase of class 1 resistance integrons (RIs) and the introduction of Pseudomonas spp. into the bacterial community. HE treatment did not reduce the CAS process performance; nevertheless it increases the risk of dissemination into the environment of bacterial species and genetic determinants (RIs) involved in antibiotic resistance acquisition.

Anaerobic co-digestion of mechanically biologically treated municipal waste with primary sewage sludge - a feasibility study.

This bench scale study investigated the suitability of MBT material for treatment by anaerobic digestion and the impacts of co-digestion of these wastes with sewage sludge. The results suggest that MBT material is amenable to anaerobic digestion with sewage sludge. The main problems for scale-up are related to the physical composition of the MBT material, the accumulation of heavy metals and other inert contaminants and the impact of both of these factors on final sludge quality. Full-scale trials would be required to assess the long-term impacts of MBT waste on anaerobic digestion, if this form of co-digestion were to be pursued. The material contamination that presents a barrier to the direct recycling of MBT material in land-applications is also a major hurdle in commercial co-digestion. Better quality input material would be likely to result in higher methane yields and fewer restrictions on the utilisation of the product in recycling.