Antibiotics in sewage treatment plants, receiving water bodies and groundwater of Chennai city and the suburb, South India: Occurrence, removal efficiencies, and risk assessment.

The presence of antibiotics in the aqueous environment can alter the water microbiome, inducing antimicrobial resistance genes. Hence, the occurrence of 18 antibiotics belonging to sulfonamides, fluoroquinolones, tetracyclines, phenicols, and macrolides classes were investigated in surface water, groundwater, and sewage treatment plants in Chennai city and the suburbs. Fluoroquinolones had the maximum detection frequency in both influent and effluent samples of urban and suburban STPs, with ofloxacin and ciprofloxacin showing the highest influent concentrations. Erythromycin was the predominant antibiotic in surface water samples with an average concentration of 194.4 ng/L. All the detected antibiotic concentrations were higher in the Buckingham Canal compared to those in Adyar and Cooum rivers, possibly due to direct sewer outfalls in the canal. In groundwater samples, ciprofloxacin showed the highest levels with an average of 20.48 ng/L and the concentrations were comparable to those of surface water. The average sulfamethazine concentration in groundwater (5.2 ng/L) was found to be slightly higher than that of the surface water and much higher than the STP influent concentrations. High levels of ciprofloxacin and sulfamethazine in groundwater may be because of their high solubility and wide use. Moreover, erythromycin was completely removed after treatment in urban STPs; FQs showed relatively lesser removal efficiency (2.4-54%) in urban STPs and (8-44%) in suburban STP. Tetracyclines and phenicols were not detected in any of the samples. Ciprofloxacin and azithromycin in surface water pose a high risk in terms of estimated antibiotic resistance. This study revealed that the measured surface water concentration of antibiotics were 500 times higher for some compounds than the predicted calculated concentrations from STP effluents. Therefore, we suspect the direct sewage outlets or open drains might play an important role in contaminating surface water bodies in Chennai city.

Residue distribution and risk assessment of two macrocyclic lactone insecticides in green onion using micro-liquid-liquid extraction (MLLE) technique coupled with liquid chromatography tandem mass spectrometry.

A micro-liquid-liquid extraction (MLLE) technique coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis was established and validated to determine the residues of two macrocyclic lactone insecticides (spinetoram and spinosad) in green onion. The limit of quantification (LOQ) of the method, as demonstrated by the lowest acceptable recovery level, was 0.01 mg kg-1, and the obtained recoveries were 78.3-93.4% with relative standard deviations (RSDs) < 12.5%. The method was then applied for analyzing field samples collected after treatment with the tested insecticides under Egyptian open-field condition. The decline pattern, terminal residues, and dietary risk assessment of spinetoram and spinosad residues in green onion were evaluated for food safety. Spinetoram and spinosad residues' decline in green onion followed first-order kinetics with the half-lives of 1.2 and 1.42 days, respectively. Based on the results, the required period to reach their respective maximum residue limits (MRLs) was 1 and 0 days for spinetoram and spinosad residues in green onion, respectively, which indicates a short persistence level and high degradation rate. The results suggest that there is no unacceptable chronic or acute risk to human health from the consumption of green onion treated with spinetoram and spinosad according to the uses considered.

An automated on-line turbulent flow liquid-chromatography technology coupled to a high resolution mass spectrometer LTQ-Orbitrap for suspect screening of antibiotic transformation products during microalgae wastewater treatment.

The evaluation of wastewater treatment capabilities in terms of removal of water pollutants is crucial when assessing water mitigation issues. Not only the monitoring of target pollutants becomes a critical point, but also the transformation products (TPs) generated. Since these TPs are very often unknown compounds, their study in both wastewater and natural environment is currently recognized as a tedious task and challenging research field. In this study, a novel automated suspect screening methodology was developed for a comprehensive assessment of the TPs generated from nine antibiotics during microalgae water treatment. Three macrolides (azithromycin, erythromycin, clarithromycin), three fluoroquinolones (ofloxacin, ciprofloxacin, norfloxacin) and three additional antibiotics (trimethoprim, pipemidic acid, sulfapyridine) were selected as target pollutants. The analysis of samples was carried out by direct injection in an on-line turbulent flow liquid chromatography-high resolution mass spectrometry (TFC-LC-LTQ-Orbitrap-MS/MS) system, followed by automatic data processing for compound identification. The screening methodology allowed the identification of 40 tentative TPs from a list of software predicted intermediates created automatically. Once known and unknown TPs were identified, degradation pathways were suggested considering the different mechanisms involved on their formation (biotic and abiotic). Results reveal microalgae ability for macrolide biotransformation, but not for other antibiotics such as for fluoroquinolones. Finally, the intermediates detected were included into an in-house library and applied to the identification of tentative TPs in real toilet wastewater treated in a microalgae based photobioreactor (PBR). The overall approach allowed a comprehensive overview of the performance of microalgae water treatment in a fast and reliable manner: it represents a useful tool for the rapid screening of wide range of compounds, reducing time invested in data analysis and providing reliable structural identification.

Occurrence of antibiotics and their impacts to primary productivity in fishponds around Tai Lake, China.

Antibiotics are widely used to improve the health and yields of farmed animals, including fish, but their use is accompanied by undesirable ecological effects. Relatively little is known about the water-body burden of antibiotics and their influence on primary productivity in aquaculture ecosystem. In this study, antibiotics usage within 24 fishponds, covering 4 areas, sampled 5 times, and having 5 fish species, was investigated surrounding Tai Lake in China. The study analyzed 15 antibiotics (including 5 sulfonamides, 2 quinolones, 3 ß-lactams, 3 tetracyclines, 1 amphenicol, and 1 macrolide), and all of them were detected in water samples, with a detection frequency of 2-60%. Sulfonamides were the most prevalent, and concentrations of sulfamethoxazole, sulfamonomethoxine, and florfenicol being over 2000 ng L(-1) in some samples, while the other antibiotics levels ranged from ND (no detection) to 551.18 ng L(-1). Significant differences were observed in antibiotic burden among different regions for total antibiotics, sulfonamides, quinolones, and amphenicols; among time points for quinolones, ß-lactams, and tetracyclines; and among species for quinolones and macrolides. Furthermore, basing on the risk quotient (RQ) method, the assessment revealed that florfenicol was of highest risk to algae with RQ values exceeding 0.1, while macrolide erythromycin posed the second highest risk. The partial correlation coefficient between total antibiotics and chlorophyll (a) was -0.035 that clearly indicated total antibiotics were detrimental to green algae growth, while the nutrient input and other physical - chemical factors were much more beneficial. Overall, holistic far-reaching measures of antibiotics control are recommended to preserve aquaculture ecosystem health.

Reduced persistence of the macrolide antibiotics erythromycin, clarithromycin and azithromycin in agricultural soil following several years of exposure in the field.

The macrolide antibiotics erythromycin, clarithromycin and azithromycin are very important in human and animal medicine, and can be entrained onto agricultural ground through application of sewage sludge or manures. In the present study, a series of replicated field plots were left untreated or received up to five annual spring applications of a mixture of three drugs to achieve a nominal concentration for each of 10 or 0.1mgkg(-1) soil; the latter an environmentally relevant concentration. Soil samples were incubated in the laboratory, and supplemented with antibiotics to establish the dissipation kinetics of erythromycin and clarithromycin using radioisotope methods, and azithromycin using HPLC-MS/MS. All three drugs were dissipated significantly more rapidly in soils with a history of field exposure to 10mgkg(-1) macrolides, and erythromycin and clarithromycin were also degraded more rapidly in field soil exposed to 0.1mgkg(-1) macrolides. Rapid mineralization of (14)C-labelled erythromycin and clarithromycin are consistent with biodegradation. Analysis of field soils revealed no carryover of parent compound from year to year. Azithromycin transformation products were detected consistent with removal of the desosamine and cladinose moieties. Overall, these results have revealed that following several years of exposure to macrolide antibiotics these are amenable to accelerated degradation. The potential accelerated degradation of these drugs in soils amended with manure and sewage sludge should be investigated as this phenomenon would attenuate environmental exposure and selection pressure for clinically relevant resistance.

Determination of spinosad at trace levels in bee pollen and beeswax with solid-liquid extraction and LC-ESI-MS.

This paper reports the use of a new LC method with a fused-core analytical column coupled to ESI-MS to determine residues of the biopesticide spinosad in bee pollen and beeswax. The method analyzes the active ingredients, spinosyns A and D, with a simple and efficient sample treatment (recovery between 90 and 105%) consisting of a solid-liquid extraction with acetone (bee pollen) or acetonitrile (beeswax). The method was validated in terms of selectivity, LOD, LOQ, linearity, and precision. The LOD and LOQ values ranged between 0.1-0.2 and 0.4-0.7 µg/kg, respectively. Moreover, the precision obtained within the linear concentration range (LOQ 500 µg/kg) was satisfactory (RSD lower than 5%). Finally, the proposed method was applied to analyze bee pollen and beeswax samples collected from apiaries located close to fruit orchards in two Spanish regions.

Persistence behaviour of milbemectin in/on tea under North-East Indian climatic condition.

A multi-location field trial was conducted under North-East Indian climatic condition viz. Siliguri and Dooars, West Bengal, India during Monsoon 2005 to evaluate the dissipation pattern of Milbemectin formulation (Milbeknock 1% EC) in/on tea field at two application rates (5 and 10 g a.i. ha(-1)). The quantitative analysis was performed using High Performance Liquid Chromatography (HPLC) with fluorescence detection at 460 nm. Following the first order kinetics the acaricide dissipates with half-life (T(1/2)) value ranges between 4.93-5.28 days and 6.84-10.76 days in made tea samples of Siliguri and Dooars field, respectively.

LC/DAD/ESI/MS method for the determination of imidacloprid, thiacloprid, and spinosad in olives and olive oil after field treatment.

The behavior in the field and the transfer from olives to olive oil during the technological process of imidacloprid, thiacloprid, and spinosad were studied. The extraction method used was effective in extracting the analytes of interest, and no interfering peaks were detected in the chromatogram. The residue levels found in olives after treatment were 0.14, 0.04, and 0.30 mg/kg for imidacloprid, thiacloprid, and spinosad, respectively, far below the maximum residue levels (MRLs) set for these insecticides in EU. At the preharvest interval (PHI), no residue was detected for imidacloprid and thiacloprid, while spinosad showed a residue level of 0.04 mg/kg. The study of the effect of the technological process on pesticide transfer in olive oil showed that these insecticides tend to remain in the olive cake. The LC/DAD/ESI/MS method showed good performance with adequate recoveries ranging from 80 to 119% and good method limits of quantitation (LOQs) and of determination (LODs). No matrix effect was detected.

Heat treatment effects on the antimicrobial activity of macrolide and lincosamide antibiotics in milk.

Antibiotic residues in milk can cause serious problems for consumers and the dairy industry. Heat treatment of milk may diminish the antimicrobial activity of these antibiotic residues. This study analyzed the effect of milk processing (60 °C for 30 min, 120 °C for 20 min, and 140 °C for 10 s) on the antimicrobial activity of milk samples fortified with three concentrations of three macrolides (erythromycin: 20, 40 and 80 µg/liter; spiramycin: 100, 200, and 400 µg/liter; and tylosin: 500, 1,000, and 2,000 µg/liter) and one lincosamide (lincomycin: 1,000, 2,000, and 4,000 µg/liter). To measure the loss of antimicrobial activity, a bioassay based on the growth inhibition of Micrococcus luteus was done. The data were analyzed using a multiple linear regression model. The results indicate that treatment at 120 °C for 20 min produces inactivation percentages of 93% (erythromycin), 64% (spiramycin), 51% (tylosin), and 5% (lincomycin), while treatment at 140 °C for 10 s results in generally lower percentages (30% erythromycin, 35% spiramycin, 12% tylosin, and 5% lincomycin). The lowest loss or lowest reduction of antimicrobial activity (21% erythromycin and 13% spiramycin) was obtained by treatment at 60 °C for 30 min.

Novel macrolide from wild strains of the phytopathogen Fungus Colletotrichum acutatum.

Three wild strains of C. acutatum have been investigated for their phytotoxic secondary metabolites involved in anthracnose disease. In addition to known compounds, a new macrolide 6 has been isolated and characterized by spectroscopic analysis.

Quantitative analysis of in vitro compatibility of binary and ternary mixtures of nitroimidazole and macrolides in combination with omeprazole using a calorimetric technique.

In the present study, in vitro interactions between nitroimidazoles, macrolides and omeprazole in binary and ternary mixtures were examined by measuring their enthalpy of solution (delta(sol)H) using a calorimetric technique. A comparison of the enthalpy of solution of the pure drugs with those of binary and ternary mixtures at pH 2 and 6 was made to indicate the magnitude of interaction between them. The delta(sol)H for all the nitroimidazoles is endothermic at pH 2 and 6 but both the macrolides show exothermic behavior, whereas the enthalpy of solution of omeprazole changes from -40.52 to 4.35 kJmol(-1) as the pH changes from 2 to 6. The results have been quantified by determining the excess enthalpy of solution for both binary and ternary systems. The small deviations from ideality for all the binary systems are attributed to various non-bonding interactions between different functional groups on both the drug molecules. The results suggest compatibility of drug pairs in their binary mixtures. However, ternary mixtures show somewhat larger interactions. The magnitude of interaction enthalpy of a ternary mixture comprising tinidazole, clarithromycin and omeprazoles which are available as a marketed kitshas been calculated to be significant, suggesting that the three drugs cannot be co-formulated.

Biological control agent of common scab disease by antagonistic strain Bacillus sp. sunhua.

AIMS: To identify an antagonistic strain against Streptomyces scabiei and to characterize the antibiotic agent. The efficacy of the isolated strain in controlling common scab disease was also evaluated. METHODS AND RESULTS: A bacterial strain antagonistic against S. scabiei was isolated from the soil of a potato-cultivating area. This bacterium was identified as a Bacillus species by 16S rRNA gene sequence analysis and was designated Bacillus sp. sunhua. Antibiotics produced by this strain were proven to be stable within a broad pH range and at high temperatures. The culture broth was extracted with ethyl acetate, and then the crude extract was applied to HPLC. Two compounds were isolated and identified as iturin A and macrolactin A by 1H-NMR, 13C-NMR, HMBC, HMQC and mass spectrometer. The culture broth of Bacillus sp. sunhua had a suppressive effect on common scab disease in a pot assay, decreasing the infection rate from 75 to 35%. This strain also suppressed Fusarium oxysporum, the pathogen of potato dry rot disease. CONCLUSIONS: Bacillus sp. sunhua was shown to inhibit S. scabiei effectively. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report demonstrating that macrolactin A and iturin A inhibit S. scabiei. This study demonstrated the possibility of controlling potato scab disease using Bacillus sp. sunhua.

Berkeleydione and berkeleytrione, new bioactive metabolites from an acid mine organism.

[structure: see text] Two novel hybrid polyketide-terpenoid metabolites were isolated from a Penicillium sp. growing in the Berkeley Pit Lake of Butte, Montana. Their structures were deduced by spectroscopic analysis and confirmed by single-crystal X-ray analysis on berkeleydione (1). Both compounds inhibited matrix metalloproteinase-3 and caspase-1, and berkeleydione showed activity toward non-small-cell lung cancer in NCI's human cell line antitumor screen.

Importancia clínica del metabolismo de medicamentos (Segunda Parte) / Clinical importance and drugs metabolism (Second Part)

Parte número dos de la segunda emisión. Esta es la segunda emisión de un trabajo científico sobre metabolismo de los medicamentos su importancia clínica. En esta segunda parte tratamos sobre las interacciones de interés más sobresalientes. Además de los mecanismos de interacción, nuestro objetivo es hacer conciencia, sobre la importancia del metabolismo de ciertos medicamentos.