Non-antibiotic Pharmaceuticals Research Articles

Non-antibiotic pharmaceuticals are toxic against Escherichia coli with no evolution of cross-resistance to antibiotics

Antimicrobial resistance can arise in the natural environment via prolonged exposure to the effluent released by manufacturing facilities. In addition to antibiotics, pharmaceutical plants also produce non-antibiotic pharmaceuticals, both the active ingredients and other components of the formulations. The effect of these on the surrounding microbial communities is less clear. We aimed to assess whether non-antibiotic pharmaceuticals and other compounds produced by pharmaceutical plants have inherent toxicity, and whether long-term exposure might result in significant genetic changes or select for cross-resistance to antibiotics. To this end, we screened four non-antibiotic pharmaceuticals (acetaminophen, ibuprofen, propranolol, metformin) and titanium dioxide for toxicity against Escherichia coli K-12 MG1655 and conducted a 30 day selection experiment to assess the effect of long-term exposure. All compounds reduced the maximum optical density reached by E. coli at a range of concentrations including one of environmental relevance, with transcriptome analysis identifying upregulated genes related to stress response and multidrug efflux in response ibuprofen treatment. The compounds did not select for significant genetic changes following a 30 day exposure, and no evidence of selection for cross-resistance to antibiotics was observed for population evolved in the presence of ibuprofen in spite of the differential gene expression after exposure to this compound. This work suggests that these compounds, at environmental concentrations, do not select for cross-resistance to antibiotics in E. coli.

Nonantibiotic Pharmaceuticals Exhibit Antibacterial Activity and Enhance Bacterial Evolution toward Antibiotic Resistance

Nonantibiotic Pharmaceuticals Exhibit Antibacterial Activity and Enhance Bacterial Evolution toward Antibiotic Resistance

Carbamazepine facilitated horizontal transfer of antibiotic resistance genes by enhancing microbial communication and aggregation

Antimicrobial resistance is a global health security issue of widespread concern. Recent studies have unveiled the potential contribution of non-antibiotics to the emergence of antimicrobial resistance. This study investigated the effect of carbamazepine, a non-antibiotic pharmaceutical, on the fate of antibiotic resistance genes (ARGs) during anaerobic digestion. The results, as revealed by both metagenomic sequencing and absolute quantification, demonstrated that carbamazepine induced the enrichment of ARGs and increased the abundance of ARGs hosts by 1.2–2.1 times. Carbamazepine facilitated microbial aggregation and intercellular communication by upregulating functional genes associated with two-component systems, quorum sensing and type IV secretion systems, thereby increasing the frequency of ARGs conjugation. Furthermore, carbamazepine induced the acquisition of ARGs by pathogens and elevated the overall pathogenic abundance. This study revealed the mechanisms of microbial self-regulation and ARGs transmission under carbamazepine stress, highlighting the potential health risks posed by non-antibiotic pharmaceuticals during the safe disposal of sludge.

Spectrum of pharmaceutical residues in commercial manure-based organic fertilizers from multi-provinces of China mainland in relation to animal farming and possible environmental risks of fertilization

With a long-term amendment of manure-based organic fertilizers (MOFs), significant elevations of antibiotics and their resistance genes in agricultural soil have aroused great concerns worldwide, but their relationships to animal farming and possible environmental risks of fertilization lack systematic studies. This study collected 41 commercial MOFs made from manures of chicken, swine, sheep/goat, and cattle, respectively, in 10 provinces (including autonomous regions) of China mainland with large animal farming industries. Twenty-nine compounds, consisting of 20 antibiotic compounds, sulfonamides' synergist (trimethoprim) and 8 non-antibiotic pharmaceuticals, were quantified in the collected MOF samples, ranging from below the quantification limits (<0.02 μg kg−1 dry mass) up to 110 mg kg−1 dry mass (oxytetracycline), using a high throughput protocol with 83 target compounds (37 antibiotic ones) of 6 pharmaceutical categories. Antibiotic compounds of tetracyclines and fluoroquinolones collectively dominated pharmaceutical residues in the MOF samples, accounting for 71.9–99.9 % of total loads, except 6 samples. Pharmaceuticals for human use only (4 antibiotic and 4 non-antibiotic compounds) and for both human and veterinary uses (5 antibiotic and 1 non-antibiotic compounds) were quantified in the MOF samples according to the Chinese pharmacopeia. The MOF samples made from chicken and swine manures (mainly captivity) had greater number, frequency, and level of the quantified pharmaceutical compounds than the ones made from sheep/goat and cattle manures (mainly grazing). Antibiotics, particularly enrofloxacin and oxytetracycline, in the MOF samples would lead to medium risks to microorganisms and invertebrates in soil and high risk to plants, and considerable risk to antibiotic resistance selection if applied in agricultural soils. Findings of this study suggest that pharmaceutical contaminations should be taken into account for the quality guidelines of the commercial MOFs as well as other pollutants (such as heavy metals), especially the MOFs made from manures of the captive chicken and swine.

Antibacterial Carbon Dots: Mechanisms, Design, and Applications.

The increase in antibiotic resistance promotes the situation of developing new antibiotics at the forefront, while the development of non-antibiotic pharmaceuticals is equally significant. In the post-antibiotic era, nanomaterials with high antibacterial efficiency and no drug resistance make them attractive candidates for antibacterial materials. Carbon dots (CDs), as a kind of carbon-based zero-dimensional nanomaterial, are attracting much attention for their multifunctional properties. The abundant surface states, tunable photoexcited states, and excellent photo-electron transfer properties make sterilization of CDs feasible and are gradually emerging in the antibacterial field. This review provides comprehensive insights into the recent development of CDs in the antibacterial field. The topics include mechanisms, design, and optimization processes, and their potential practical applications are also highlighted, such as treatment of bacterial infections, against bacterial biofilms, antibacterial surfaces, food preservation, and bacteria imaging and detection. Meanwhile, the challenges and outlook of CDs in the antibacterial field are discussed and proposed.

Preliminary insights into the action of non-antibiotic pharmaceuticals in the colonization of Pseudomonas aeruginosa TGC04

Molecules with antimicrobial properties, such as those found in non-antibiotic pharmaceuticals, may pressure bacteria to adapt to the environment. In this work, five of the most sold non-antibiotic pharmaceuticals in Brazil and in Egypt in 2020 (losartan 50 mg, acetylsalicylic acid 100 mg, diclofenac 50 mg, paracetamol 750 mg and metformin 500 mg and dipyrone 100 mg/mL), were tested against the wild strain Pseudomonas aeruginosa TGC04, previously isolated by our group and which has been characterized over the years. We evaluated inhibition of biofilm adhesion over 48 h using the crystal violet test. Exposure of P. aeruginosa TGC04 to the compounds promoted a similar moderate reduction in adherence for all the pharmaceuticals tested, amounting to about 60%. This indicated that the cells were also moderately adherent. However, although all non-antibiotic pharmaceuticals did not produce a biocidal effect on the wild strain, intense antibiofilm activity was observed, except for paracetamol.

Estimating the Mass of Pharmaceuticals Harbored in Municipal Solid Waste Landfills by Analyzing Refuse Samples at Various Ages and Depths.

Pharmaceuticals have been detected at high concentrations in municipal solid waste (MSW) landfill leachates, which are recognized as an underestimated source of pharmaceutical residues in the environment. However, limited efforts have been made to characterize pharmaceuticals in MSW landfill refuse, which is also of significant concern given the potential long-term environmental impact. Herein, we excavated landfill refuse from six cells with landfill ages of 7-27 years in the largest MSW landfill in Shanghai (in each cell, landfill refuse was collected from different depths of 2-8 m) and analyzed samples for the presence of 55 pharmaceuticals, including antibiotics and non-antibiotics. The results reveal the presence of 42 pharmaceuticals in landfill refuse, with median concentrations ranging from 0.30 to 116 μg/kg. Antibiotic and non-antibiotic pharmaceuticals exhibited diverse concentration trends with age, related to changes in policy intervention and consumption over time. Different concentration variations of individual pharmaceuticals were observed in refuse samples excavated at different depths and positively correlated to their sorption ability. The mass of pharmaceuticals in the investigated landfill was estimated from the obtained concentrations to be 80-220 tons with 95% probability, based on Monte Carlo analysis. To the best of our knowledge, this study provides the first estimate of pharmaceutical mass in an MSW landfill. The results will be helpful for understanding the potential long-term environmental impact of pharmaceuticals in landfills.

A new insight into the potential drivers of antibiotic resistance gene enrichment in the collembolan gut association with antibiotic and non-antibiotic agents

Effects of non-antibiotic pharmaceuticals on antibiotic resistance genes (ARGs) in soil ecosystem are still unclear. In this study, we explored the microbial community and ARGs variations in the gut of the model soil collembolan Folsomia candida following soil antiepileptic drug carbamazepine (CBZ) contamination, while comparing with antibiotic erythromycin (ETM) exposure. Results showed that, CBZ and ETM all significantly influenced ARGs diversity and composition in the soil and collembolan gut, increasing the relative abundance of ARGs. However, unlike ETM, which influences ARGs via bacterial communities, exposure to CBZ may have primarily facilitated enrichment of ARGs in gut through mobile genetic elements (MGEs). Although soil CBZ contamination did not pose an effect on the gut fungal community of collembolans, it increased the relative abundance of animal fungal pathogens contained therein. Soil ETM and CBZ exposure both significantly increased the relative abundance of Gammaproteobacteria in the collembolan gut, which may be used to indicate soil contamination. Together, our results provide a fresh perspective for the potential drivers of non-antibiotic drugs on ARG changes based on the actual soil environment, revealing the potential ecological risk of CBZ on soil ecosystems involving ARGs dissemination and pathogens enrichment.

Non-antibiotic pharmaceuticals promote conjugative plasmid transfer at a community-wide level

BackgroundHorizontal gene transfer (HGT) plays a critical role in the spread of antibiotic resistance and the evolutionary shaping of bacterial communities. Conjugation is the most well characterized pathway for the spread of antibiotic resistance, compared to transformation and transduction. While antibiotics have been found to induce HGT, it remains unknown whether non-antibiotic pharmaceuticals can facilitate conjugation at a microbial community-wide level.ResultsIn this study, we demonstrate that several commonly consumed non-antibiotic pharmaceuticals (including carbamazepine, ibuprofen, naproxen and propranolol), at environmentally relevant concentrations (0.5 mg/L), can promote the conjugative transfer of IncP1-α plasmid-borne antibiotic resistance across entire microbial communities. The over-generation of reactive oxygen species in response to these non-antibiotic pharmaceuticals may contribute to the enhanced conjugation ratios. Cell sorting and 16S rRNA gene amplicon sequencing analyses indicated that non-antibiotic pharmaceuticals modulate transconjugant microbial communities at both phylum and genus levels. Moreover, microbial uptake ability of the IncP1-α plasmid was also upregulated under non-antibiotic pharmaceutical exposure. Several opportunistic pathogens, such as Acinetobacter and Legionella, were more likely to acquire the plasmid conferring multidrug resistance.ConclusionsConsidering the high possibility of co-occurrence of pathogenic bacteria, conjugative IncP1-α plasmids and non-antibiotic pharmaceuticals in various environments (e.g., activated sludge systems), our findings illustrate the potential risk associated with increased dissemination of antibiotic resistance promoted by non-antibiotic pharmaceuticals in complex environmental settings.A5CekS1hSG7sRJ8ebfxUwdVideo abstract

Paclitaxel and its derivative facilitate the transmission of plasmid-mediated antibiotic resistance genes through conjugative transfer

The rapid dissemination of antibiotic resistance by horizontal gene transfer (HGT) renders the global resistance crisis more tense and urgent as few effective antimicrobials are available to combat multidrug-resistant (MDR) pathogens at present. Conjugation is one of the most dominant and representative pathways of HGT. Antibiotic residue in environment is recognized as an important accelerator for conjugal transfer, whereas the roles of non-antibiotic pharmaceuticals in this process are not fully understood. Here we found that environmentally relevant concentrations of paclitaxel as well as its derivative docetaxel, two commonly used anticancer drugs, remarkably facilitated the conjugative transfer of resistance plasmids carrying multiple antibiotic resistance genes (ARGs). The underlying mechanisms accounting for the enhanced conjugation were investigated by detecting the activity of RpoS regulon, membrane permeability, SOS response and gene expression of conjugative transfer systems. Our results showed that paclitaxel induced a series of cellular responses, including up-regulation of rpoS expression, activated SOS response, increased cell membrane permeability, enhanced plasmid replication and mating pilus formation. Collectively, our data provide new insight on the roles of paclitaxel and its derivative in promoting the conjugal transfer of ARGs, highlighting the importance of good antimicrobial stewardship.

Anthropogenic activities and seasonal properties jointly drive the assemblage of bacterial communities in subtropical river basins

Anthropogenic activities have inevitably impacted riverine ecosystems, yet their overall contribution to the assemblage of bacterial communities at a large river basin scale remains unclear. In this study, 16S amplicon sequencing was implemented to investigate the bacterial ecosystems in paired water and sediment of North River and West River basins in South China., which contains various anthropogenic environments (e.g., rural/urban area, mining area and livestock area). Subsequently, the links between bacterial community and various types of emerging pollutants in river water were analyzed. The results show that the bacterial assemblage of water and sediment had their own properties that the bacterial community of sediment were mainly affected by seasonal properties, while the bacterial community of water were affected by both seasons and anthropogenic activities. Therein, the aquatic bacterial compositions and abundances were driven by changes in temperature, dissolved oxygen and the emerging pollutants. The dominant phyla Proteobacteria and Firmicutes exhibited adaptability to the mining-affected regions, therein many clades (e.g., Beijerinckiaceae, Acetobacteraceae and Mycobacteriaceae) were also prevalent in the livestock-affected and densely-populated regions. In addition, these two phyla presented associations to the antibiotic resistance in water. The levels of antibiotics, relative antibiotic resistance gens (ARGs) and non-antibiotic pharmaceuticals (NAPs) were closely related to bacterial community composition, diversity and functional diversity, indicating their drive in shifting bacterial communities. Collectively, this work provides a basis for understanding the contribution of anthropogenic activities in shifting bacterial community at a large river basin scale. Further, the results provide new insights for expansion of ecological assessment.

Effect of concentration and hydraulic reaction time on the removal of pharmaceutical compounds in a membrane bioreactor inoculated with activated sludge.

SummaryPharmaceuticals are often not fully removed in wastewater treatment plants (WWTPs) and are thus being detected at trace levels in water bodies all over the world posing a risk to numerous organisms. These organic micropollutants (OMPs) reach WWTPs at concentrations sometimes too low to serve as growth substrate for microorganisms; thus, co‐metabolism is thought to be the main conversion mechanism. In this study, the microbial removal of six pharmaceuticals was investigated in a membrane bioreactor at increasing concentrations (4–800 nM) of the compounds and using three different hydraulic retention times (HRT; 1, 3.5 and 5 days). The bioreactor was inoculated with activated sludge from a municipal WWTP and fed with ammonium, acetate and methanol as main growth substrates to mimic co‐metabolism. Each pharmaceutical had a different average removal efficiency: acetaminophen (100%) > fluoxetine (50%) > metoprolol (25%) > diclofenac (20%) > metformin (15%) > carbamazepine (10%). Higher pharmaceutical influent concentrations proportionally increased the removal rate of each compound, but surprisingly not the removal percentage. Furthermore, only metformin removal improved to 80–100% when HRT or biomass concentration was increased. Microbial community changes were followed with 16S rRNA gene amplicon sequencing in response to the increment of pharmaceutical concentration: Nitrospirae and Planctomycetes 16S rRNA relative gene abundance decreased, whereas Acidobacteria and Bacteroidetes increased. Remarkably, the Dokdonella genus, previously implicated in acetaminophen metabolism, showed a 30‐fold increase in abundance at the highest concentration of pharmaceuticals applied. Taken together, these results suggest that the incomplete removal of most pharmaceutical compounds in WWTPs is dependent on neither concentration nor reaction time. Accordingly, we propose a chemical equilibrium or a growth substrate limitation as the responsible mechanisms of the incomplete removal. Finally, Dokdonella could be the main acetaminophen degrader under activated sludge conditions, and non‐antibiotic pharmaceuticals might still be toxic to relevant WWTP bacteria.

Non-antibiotic pharmaceuticals promote the transmission of multidrug resistance plasmids through intra- and intergenera conjugation

Antibiotic resistance is a global threat to public health. The use of antibiotics at sub-inhibitory concentrations has been recognized as an important factor in disseminating antibiotic resistance via horizontal gene transfer. Although non-antibiotic, human-targeted pharmaceuticals are widely used by society (95% of the pharmaceuticals market), the potential contribution to the spread of antibiotic resistance is not clear. Here, we report that commonly consumed, non-antibiotic pharmaceuticals, including nonsteroidal anti-inflammatories (ibuprofen, naproxen, diclofenac), a lipid-lowering drug (gemfibrozil), and a β-blocker (propranolol), at clinically and environmentally relevant concentrations, significantly accelerated the dissemination of antibiotic resistance via plasmid-borne bacterial conjugation. Various indicators were used to study the bacterial response to these drugs, including monitoring reactive oxygen species (ROS) and cell membrane permeability by flow cytometry, cell arrangement, and whole-genome RNA and protein sequencing. Enhanced conjugation correlated well with increased production of ROS and cell membrane permeability. Additionally, these non-antibiotic pharmaceuticals induced responses similar to those detected when bacteria are exposed to antibiotics, such as inducing the SOS response and enhancing efflux pumps. The findings advance understanding of the transfer of antibiotic resistance genes, emphasizing the concern that non-antibiotic, human-targeted pharmaceuticals enhance the spread of antibiotic resistance among bacterial populations.

Evidence for selection of multi-resistant E. coli by hospital effluent

There is a risk that residues of antibiotics and other antimicrobials in hospital and municipal wastewaters could select for resistant bacteria. Still, direct experimental evidence for selection is lacking. Here, we investigated if effluent from a large Swedish hospital, as well as influent and effluent from the connected municipal wastewater treatment plant (WWTP) select for antibiotic resistant Escherichia coli in three controlled experimental setups. Exposure of sterile-filtered hospital effluent to a planktonic mix of 149 different E. coli wastewater isolates showed a strong selection of multi-resistant strains. Accordingly, exposure to a complex wastewater community selected for strains resistant to several antibiotic classes. Exposing individual strains with variable resistance patterns revealed a rapid bactericidal effect of hospital effluent on susceptible, but not multi-resistant E. coli. No selection was observed after exposure to WWTP effluent, while exposure to WWTP influent indicated a small selective effect for ceftazidime and cefadroxil resistant strains, and only in the E. coli mix assay. An analysis of commonly used antibiotics and non-antibiotic pharmaceuticals in combination with growth and resistance pattern of individual E. coli isolates suggested a possible contribution of ciprofloxacin and β-lactams to the selection by hospital effluent. However, more research is needed to clarify the contribution from different selective agents. While this study does not indicate selection by the studied WWTP effluent, there is some indications of selective effects by municipal influent on β-lactam-resistant strains. Such effects may be more pronounced in countries with higher antibiotic use than Sweden. Despite the limited antibiotic use in Sweden, the hospital effluent strongly and consistently selected for multi-resistance, indicating widespread risks. Hence, there is an urgent need for further evaluation of risks for resistance selection in hospital sewers, as well as for strategies to remove selective agents and resistant bacteria.

Non-antibiotic pharmaceuticals enhance the transmission of exogenous antibiotic resistance genes through bacterial transformation

Antibiotic resistance is a serious global threat for public health. Considering the high abundance of cell-free DNA encoding antibiotic resistance genes (ARGs) in both clinical and environmental settings, natural transformation is an important horizontal gene transfer pathway to transmit antibiotic resistance. It is acknowledged that antibiotics are key drivers for disseminating antibiotic resistance, yet the contributions of non-antibiotic pharmaceuticals on transformation of ARGs are overlooked. In this study, we report that some commonly consumed non-antibiotic pharmaceuticals, at clinically and environmentally relevant concentrations, significantly facilitated the spread of antibiotic resistance through the uptake of exogenous ARGs. This included nonsteroidal anti-inflammatories, ibuprofen, naproxen, diclofenac, the lipid-lowering drug, gemfibrozil, and the β-blocker propranolol. Based on the results of flow cytometry, whole-genome RNA sequencing and proteomic analysis, the enhanced transformation of ARGs was affiliated with promoted bacterial competence, enhanced stress levels, over-produced reactive oxygen species and increased cell membrane permeability. In addition, a mathematical model was proposed and calibrated to predict the dynamics of transformation during exposure to non-antibiotic pharmaceuticals. Given the high consumption of non-antibiotic pharmaceuticals, these findings reveal new concerns regarding antibiotic resistance dissemination exacerbated by non-antibiotic pharmaceuticals.

Occurrence and ecological risk of pharmaceuticals and personal care products (PPCPs) and pesticides in typical surface watersheds, China

To evaluate the occurrence and ecological risk of organic contaminants in aquatic environment in China, a method for simultaneously detecting 130 pharmaceuticals and personal care products (PPCPs) and 35 pesticides has been established using solid phase extraction-ultra performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS) method. In the present survey, a total of 122 target compounds (103 PPCPs and 19 pesticides) were detected in seven major watersheds in China, with average concentrations ranged from 0.02 ng/L (sulfamerazine) to 332.75 ng/L (bisphenol A), revealing that PPCPs and pesticides were widely distributed in surface water of China. Antibiotics and organophosphorus were the most ubiquitously PPCPs and pesticides, respectively; quinolones were the predominant antibiotics, most of which were detected in more than 96% sampling sites, with average concentrations ranged from 2.14 to 309.67 ng/L; six pesticides including isoprocarb, fenobucarb, acetamiprid, imidacloprid, acetochlor and bentazone were detected in more than 80% sampling sites, with average concentrations ranged from 5.62 to 225.93 ng/L; more than half of the non-antibiotic pharmaceuticals were hormones; and diethyltoluamide (DEET) was predominant personal care products; The risk assessment showed that each watershed was at potential medium ecological risk based on their mean concentration (RQTotal > 1), and pesticides were the main compounds arising risks.

Spatiotemporal distributions, source apportionment and potential risks of 15 pharmaceuticals and personal care products (PPCPs) in Qinzhou Bay, South China

In the present study, we investigated the spatiotemporal distributions and risks of 15 non-antibiotic pharmaceuticals and personal care products (PPCPs) in surface water collected from Qinzhou Bay, China during the summer and winter of 2017. Our results showed that 14 out of the 15 target PPCPs were detected, and they had higher concentrations in the winter than the summer, except for N, N-diethyl-m-toluamide and indomethacin. Furthermore, N, N-diethyl-m-toluamide and caffeine respectively were the dominant contaminants in the summer and winter, with their highest concentrations up to 33.7 ng/L and 26.8 ng/L. Generally, concentrations of PPCPs were higher in the inner bay than outer bays, with untreated sewage and effluents of sewage treatment plants (STPs) as main pollution sources. The results of the risk assessment indicate that diclofenac may pose risks to aquatic organisms. Overall, our results provided occurrence and important insights into the risk management of PPCPs in Qinzhou Bay.

Antiepileptic drug carbamazepine promotes horizontal transfer of plasmid-borne multi-antibiotic resistance genes within and across bacterial genera

Antibiotic resistance is a severe global threat for public health, causing around 700,000 deaths per year. Horizontal gene transfer (HGT) is one of the most significant pathways to disseminate antibiotic resistance. It is commonly acknowledged that sub-minimum inhibition concentrations of antibiotics are major contributors in promoting antibiotic resistance through HGT. Pharmaceuticals are occurring in our environments at increased levels, yet little is known whether non-antibiotic pharmaceuticals cause or accelerate the dissemination of antibiotic resistance. Here, we report for the first time that the antiepileptic drug, carbamazepine, promotes conjugative transfer of antibiotic resistance genes. It was seen that environmentally relevant concentrations of carbamazepine (e.g., 0.05 mg/L) significantly enhanced the conjugative transfer of multiresistance genes carried by plasmid within and across bacterial genera. The underlying mechanisms of the enhanced HGT were revealed by detecting oxidative stress and cell membrane permeability, in combination with MinION DNA sequencing, genome-wide RNA sequencing, and proteomic analysis. Carbamazepine induced a series of acute responses, including increased levels of reactive oxygen species, the SOS response; increased cell membrane permeability, and pilus generation. Expressional levels of genes related to these processes were significantly upregulated during carbamazepine exposure. Given that HGT occurs widely among different species in various environments, these findings are an early warning for a wide assessment of the roles of non-antibiotic pharmaceuticals in the spread of antibiotic resistance.

Occurrence of pharmaceuticals and personal care products, and their associated environmental risks in a large shallow lake in north China.

Eighteen selected pharmaceuticals and personal care products (PPCPs), consisting of five non-antibiotic pharmaceuticals (N-APs), four sulfonamides (SAs), four tetracyclines (TCs), four macrolides (MCs), and one quinolone (QN) were detected in water, pore water, and sediment samples from Baiyangdian Lake, China. A total of 31 water samples and 29 sediment samples were collected in March 2017. Caffeine was detected with 100% frequency in surface water, pore water, and sediment samples. Carbamazepine was detected with 100% frequency in surface water and sediment samples. Five N-APs were prominent, with mean concentrations of 4.90-266.24ng/l in surface water and 5.07-14.73μg/kg in sediment samples. Four MCs were prominent, with mean concentrations of 0.97-29.92ng/l in pore water samples. The total concentrations of the different classes of PPCPs followed the order: N-APs (53.26%)>MCs (25.39)>SAs (10.06%)>TCs (7.64%)>QNs (3.64%) in surface water; N-APs (42.70%)>MCs (25.43%)>TCs (14.69%)>SAs (13.90%)>QNs (3.24%) in sediment samples, and MCs (42.12%)>N-APs (34.80%)>SAs (11.71%)>TCs (7.48%)>QNs (3.88%) in pore water samples. The geographical differences of PPCP concentrations were largely due to anthropogenic activities. Sewage discharged from Baoding City and human activities around Baiyangdian Lake were the main sources of PPCPs in the lake. An environmental risk assessment for the upper quartile concentration was undertaken using calculated risk quotients and indicated a low or medium-high risk from 18 PPCPs in Baiyangdian Lake and its five upstream rivers.

Resensitization of methicillin-resistant Staphylococcus aureus by amoxapine, an FDA-approved antidepressant

The rapid increase in bacterial resistance to antibiotics is a global healthcare crisis. Non-antibiotic pharmaceuticals that have attained approval by the United States Food and Drug Administration have the potential to be repurposed as bacterial resistance-modifying agents and therefore could become valuable resources in our battle against antibiotic-resistant microbes. Amoxapine is a tetracyclic antidepressant used in the treatment of major depressive disorder. Here we demonstrate the ability of amoxapine to resensitize methicillin-resistant Staphylococcus aureus strain ATCC 43300 to oxacillin in both agar diffusion and broth microdilution assays. Amoxapine also reduced the bacterial cleavage of nitrocefin in a dose-dependent manner, suggesting that it may exert its adjuvant effects through reduction of beta-lactamase activity.