Clinical, economic, and societal burden of cystic fibrosis and the impact of the CFTR modulator, lumacaftor/ivacaftor: an assessment using linked registry data in Sweden.

AIMS: We aimed to describe the clinical, economic, and societal burdens of cystic fibrosis (CF) and impact of CF transmembrane conductance regulator modulator (CFTRm) treatment on people with CF, caregivers, and healthcare systems. MATERIAL AND METHODS: This retrospective study used linked real-world data from Swedish national population-based registries and the Swedish CF Quality Registry to assess clinical, economic, and societal burden and CFTR impact in CF. Records from people with CF and a ten-fold control population without CF matched by sex, birth year, and location were compared during 2019. Outcomes for a subset aged >6 years initiating lumacaftor/ivacaftor (LUM/IVA) in 2018 were compared 12 months pre- and post-treatment initiation. RESULTS: People with CF (n = 743) had >10 times more inpatient and outpatient specialist visits annually vs controls (n = 7406). Those aged >18 had an additional 77·7 (95% CI: 70·3, 85·1) days of work absence, at a societal cost of €11,563 (95% CI: 10,463, 12,662), while caregivers of those aged <18 missed an additional 6.1 (5.0, 7.2) workdays. With LUM/IVA treatment, people with CF (n = 100) had significantly increased lung function (mean change in ppFEV1 [3·8 points; 95% CI: 1·1, 6·6]), on average 0·5 (95% CI: -0·8, -0·2) fewer pulmonary exacerbations and 45·2 (95% CI: 13·3, 77·2) fewer days of antibiotics. Days of work lost by caregivers of people with CF aged <18 decreased by 5·4 days (95% CI: 2·9, 7·9). CONCLUSION: CF is associated with a high clinical economic and societal burden in Sweden. Improvements in clinical status observed in people with CF treated with LUM/IVA were reflected in reduced caregiver and societal burden.

Cystic fibrosis (CF) is a disease caused by a single faulty gene called CFTR, which affects the lungs, pancreas, and other organs. Medications known as CFTR modulators help improve the function of this faulty gene and have shown benefits for people with CF. In Sweden, two such medicines, lumacaftor and ivacaftor (LUM/IVA), have been available since July 2018 for treating CF. This study looks at the impact of CF on patients, caregivers, and the healthcare system, as well as the benefits of CFTR modulators. Using data from Swedish national healthcare and social insurance registries, the study compared 743 people with CF in 2019 to about 7400 people without CF, matched by sex, birth year, and location. The findings show that people with CF had 24 times higher direct healthcare costs, including outpatient visits, hospitalizations, and CF-related medications, totaling 23,233 Euros. Indirect costs, such as work absences for those over 18 with CF anssd caregivers' absences to care for sick children, were 9,629 Euros, which is five times higher than the general population. Those over 6 years old treated with LUM/IVA showed improved lung health, reduced hospitalizations (though not significantly), and needed fewer antibiotics. Caregivers' work absences decreased, but there was no change in work absences for adults with CF. Overall, treatment with LUM/IVA improved clinical outcomes and reduced the burden on caregivers and society.

International disparities in diagnosis and treatment access for cystic fibrosis.

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI) has revolutionized cystic fibrosis (CF) treatment. However, previous research has demonstrated profound global disparities in diagnosis and treatment access. If unaddressed, these threaten to widen existing health inequities. Therefore, in this analysis we aimed to reappraise gaps and evaluate progress in diagnosis and treatment equity in high-income (HIC) versus low- and middle-income countries (LMICs). METHODS: Estimates of the global CF population were made in 158 countries using patient registries, systematic literature searches, and an international survey of 14 CF experts. Estimates of the global burden of undiagnosed CF were made using epidemiological studies identified in literature searches and registry coverage data. The proportion of people receiving ETI was estimated using publicly available revenue data and a survey of 23 national drug pricing databases. RESULTS: 188,336 (163,421-209,204) people are estimated to have CF in 96 countries. Of these, 111,767 (59%) were diagnosed and 51,322 (27%) received ETI. The undiagnosed patient burden is estimated to be 76,569 people, with 82% in LMICs. ETI is reimbursed in 35 HICs, but only one LMIC. Four years after approval, there are 13,723 people diagnosed with CF who live in a country where ETI is inaccessible. This increases to 76,199 when including the estimated undiagnosed population. CONCLUSIONS: Equitable access to CFTR modulators must become a top priority for the international CF community. ETI costs up to $322,000 per year but could be manufactured for $5000 to allow access under a voluntary license. Given the extent of disparities, other mechanisms to improve access that circumvent the manufacturer should also be considered.

Comprehensive Assessment of CFTR Modulators' Therapeutic Efficiency for N1303K Variant.

p.Asn1303Lys (N1303K) is a common missense variant of the CFTR gene, causing cystic fibrosis (CF). In this study, we initially evaluated the influence of CFTR modulators on the restoration of N1303K-CFTR function using intestinal organoids derived from four CF patients expressing the N1303K variant. The forskolin-induced swelling assay in organoids offered valuable insights about the beneficial effects of VX-770 + VX-661 + VX-445 (Elexacaftor + Tezacaftor + Ivacaftor, ETI) on N1303K-CFTR function restoration and about discouraging the prescription of VX-770 + VX-809 (Ivacaftor + Lumacaftor) or VX-770 + VX-661 (Ivacaftor + Tezacaftor) therapy for N1303K/class I patients. Then, a comprehensive assessment was conducted on an example of one patient with the N1303K/class I genotype to examine the ETI effect on the restoration of N1303K-CFTR function using in vitro the patient's intestinal organoids, ex vivo the intestinal current measurements (ICM) method and assessment of the clinical status before and after targeted therapy. All obtained results are consistent with each other and have proven the effectiveness of ETI for the N1303K variant. ETI produced a significant positive effect on forskolin-induced swelling in N1303K/class I organoids indicating functional improvement of the CFTR protein; ICM demonstrated that ETI therapy restored CFTR function in the intestinal epithelium after three months of treatment, and the patient improved his clinical status and lung function, increased his body mass index (BMI) and reduced the lung pathogenic flora diversity, surprisingly without improving the sweat test results.

In Vitro Assessment of Antimicrobial Activity of Novel Fluoroquinolone, Levonadifloxacin (WCK 771) Against Multi-Drug-Resistant Clinical Isolates from Cancer Patients in India.

Introduction: Rapid increase in antimicrobial-resistance is leading to urgent need for newer broad-spectrum antimicrobials. Therefore, we have evaluated the antimicrobial résistance spectrum of India-discovered novel antibiotics (levonadifloxacin) against clinical isolates recovered from cancer patients. Materials and Methods: The study was conducted in the microbiology department, over a period of 1 year between May 2021 and June 2022 and 374 consecutive and nonduplicate Gram-positive (GPC) and MDR Gram Negative Bacteria (GNB) isolate were analyzed from 3,880 cancer patients in study. The identification and antimicrobial sensitivities of bacterial isolates were performed according to standard laboratory protocols by using automated identification system (VITEK-2-8.01; BioMérieux, Germany). The activity of levonadifloxacin and comparator antibiotics was evaluated using disk diffusion methods as per Clinical and Laboratory Standards Institute 2022 guidelines. Results: The mean age of the patients were 51.6 ± 14.59 years with male: female ratio of 1.2:1. The prevalence of GPC was 167 (44.65%) and MDR-GNB was 207 (55.34%). The most common GPC was Staphylococcus aureus; 97 (58.08%) followed by Enterococcus species 66 (39.52%). In GNB, Escherichia coli; 93 (44.92%) was the most common followed by Klebsiella pneumoniae; 45 (21.73%). Levonadifloxacin susceptibility was present in 98.7% methicillin-resistant S. aureus and 96% methicillin-susceptible S. aureus and 77.1% Enterococcus-species. Additionally, all the fluoroquinolones-resistant S. aureus isolates were susceptible to levonadifloxacin (WCK-771) except one isolate. Also, levonadifloxacin-(WCK-771) exhibits 100% susceptibility fluoroquinolone susceptible GNB, such as E. coli, K. pneumoniae, Pseudomonas species, and Acinetobacter species. Interestingly, all fluoroquinolones-resistant Salmonella species and Stenotrophomonas maltophilla exhibited 100% susceptibility to levonadifloxacin (WCK-771). Conclusion: Levonadifloxacin (WCK-771) possesses potent activity against all the MDR Gram-positive pathogens including the coverage of susceptible Enterobacterales and MDR S. maltophilla and Burkholderia cepacia suggesting its potential utility in the management of polymicrobial infections.

Longitudinal Effects of Elexacaftor/Tezacaftor/Ivacaftor: Multidimensional Assessment of Neuropsychological Side Effects and Physical and Mental Health Outcomes in Adolescents and Adults.

BACKGROUND: Italy initiated elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (pwCF) in July 2021. It has led to dramatic improvements in lung function, BMI, sweat chloride, and respiratory symptoms. However, few data are available on side effects or effects on a broad range of outcomes. RESEARCH QUESTION: How does ETI affect mental health, cognitive processing, neuropsychological side effects, GI symptoms, and health-related quality of life over time? STUDY DESIGN AND METHODS: This was a prospective, "real-world" longitudinal study. Participants were recruited consecutively and evaluated at initiation (T0) and after 1 month, 3 months, and 6 months of starting treatment. Assessments included depression (nine-item Patient Health Questionnaire), anxiety (seven-item Generalized Anxiety Disorder), cognition (Symbol Digit Modalities Test), GI Symptom Tracker, and health-related quality of life (Cystic Fibrosis Questionnaire-Revised). Based on literature, an ad hoc questionnaire was developed to assess side effects: insomnia, headache, memory problems, "brain fog," and concentration problems. Following descriptive analyses, longitudinal data were analyzed by using mixed models for repeated measures, controlling for age and sex when appropriate. RESULTS: Ninety-two consecutive pwCF (female/male, 46/46; mean age, 25.4 years) participated. FEV1 increased initially and then remained stable. BMI also increased significantly from T0 to 6 months (P < .01). Depression improved from T0 to 1 month (P < .001); however, no changes in anxiety were found. Cognitive processing improved from T0 to subsequent assessments. Positive changes were reported on the GI Symptom Tracker for stools and adherence challenges, although no changes were found for abdominal pain and digestion. Side effects occurred in 10% to 29%, with no reduction over time; insomnia increased significantly across time. Female participants reported more side effects than male participants (ie, insomnia, headache, concentration problems, brain fog). INTERPRETATION: This prospective study evaluated the effects of ETI using multiple measures. Significant improvements were found in many domains; however, side effects were reported by a substantial proportion of pwCF, with no improvements over time. Female participants reported more side effects than male participants. pwCF should be followed up systematically to assess the frequency of side effects after starting this new modulator.

Plackett-Burman and face-centered composite designs for development and optimization of chromatographic method for the simultaneous determination of glycopyrronium, indacaterol and mometasone in their fixed dose combination inhaler - Green profile assessment.

A novel simple, specific, sensitive, accurate and precise reversed phase high performance liquid chromatographic method (RP-HPLC/UV) was developed and validated for the simultaneous estimation of Glycopyrronium bromide (GLY), Indacaterol acetate (IND) and Mometasone furoate (MOF) in pure form, in laboratory prepared mixtures and in pharmaceutical dosage form. Experimental design methodology was applied by using Plackett-Burman and face-centered composite designs to achieve the best resolution with minimum experimental trials. The designed model was statistically analyzed, graphically presented by surface plots and the relationships between coefficients of the derived polynomial equations were interpreted. Chromatographic separation was achieved on Inertsil ODS C18 column (250 ×4.6 mm, 5 µm) at ambient temperature using a mobile phase composed of methanol: 0.1% glacial acetic acid (pH4) in a gradient elution at a flow rate 1 mL /min. UV detection was carried out at 233 nm. Response was found to be linear in the concentration range of 20-120 µg /mL with regression coefficient (r2 = 0.999) for GLY, 50-300 µg /mL with regression coefficient (r2 = 0.9995) for IND and 50-300 µg /mL with regression coefficient (r2 = 0.9998) for MOF. The method was validated as per ICH guidelines and satisfactory results were achieved. The method was successfully applied for the analysis of the cited drugs in their fixed dose combination (FDC) pharmaceutical formulation. Statistical comparison between the results obtained by the proposed method and the reference methods for GLY, IND and MOF showed no significant difference. The developed method could be implemented in quality control aspects of the cited drugs. Four green metrics were used to evaluate the new RP-HPLC/UV method's greenness and compare it to other published techniques.

Urinary antibiotic concentrations in preschool children from eastern China and health risk assessment.

Despite limited biomonitoring studies suggesting extensive antibiotic exposure in general population, the body burden of antibiotics in young children and their potential health risks remain unclear. To assess the antibiotic exposure levels in young children, 508 preschoolers aged 3-6 years were recruited from eastern China in 2022, and a total of 50 representative antibiotics from 8 categories, including 17 human antibiotics (HAs), 4 antibiotics preferred as HAs (PHAs), 16 veterinary antibiotics (VAs), and 13 antibiotics preferred as VAs (PVAs), were analyzed by UPLC-MS/MS. Hazard quotient (HQ) and hazard index (HI) were calculated to evaluate the health risks, and multivariate logistic regression was applied to examine diet with antibiotic exposure. Our results showed that there were 41 antibiotics detected in children's urine, and the overall detection frequency was as high as 100%. Sulfonamides, macrolides, ß-lactams, quinolones, and azoles were the predominant categories of antibiotic detected. Among the studied children, 6.5% had a sum of estimated daily intake (EDI) of all VAs and PVAs larger than 1 µg/kg/day. Notably, 10.0% of the children had a microbiological HI value exceeding 1, primarily contributed by ciprofloxacin. Children with higher consumption of seafood had a relatively increased exposure to multiple categories of antibiotics, including HAs, VAs, quinolones, azoles, and others. Principal component analysis suggested that "Aquatic products and viscera preferred dietary pattern" scores were positively correlated with the exposure levels of ciprofloxacin (OR: 1.23; 95% CI: 1.02-1.47) and carbadox (OR: 1.32; 95% CI: 1.10-1.59), and a relatively increased exposure of PHAs was realized in children with higher "Meat-egg preferred dietary pattern" scores (OR: 1.24; 95% CI: 1.03-1.50). In conclusion, there was a widespread exposure to antibiotics among preschool children from eastern China, and children who consumed more animal-derived foods may had an increased exposure to antibiotics.

[Spatial-temporal Distribution and Risk Assessment of Quinolones Antibiotics in Soil of Shijiazhuang City].

Due to their importance in human medicine, quinolones (QNs), as a typical class of antibiotics, are considered to be the "highest priority critically important antimicrobials" by the World Health Organization (WHO). In order to clarify the spatial-temporal variation and risk of QNs in soil, 18 representative topsoil samples were respectively collected in September 2020 (autumn) and June 2021 (summer). The contents of QNs antibiotics in soil samples were determined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and the ecological risk and resistance risk were calculated using the risk quotient method (RQ). The results showed that:① the average content of QNs decreased from autumn to summer (the average contents of QNs were 94.88 µg·kg-1in autumn and 44.46 µg·kg-1 in summer); the highest values appeared in the middle area. ② The average proportion of silt was without change, whereas the average proportion of clay and sand was increased and decreased, respectively; the average contents of total phosphorus (TP), ammonia nitrogen (NH4+-N), and nitrate nitrogen (NO3--N) also decreased. ③ The content of QNs was significantly correlated with soil particle size, nitrite nitrogen (NO2--N), and nitrate nitrogen (NO3--N) (P<0.05). ④ The combined ecological risk of QNs showed high risk level (RQsum>1), whereas the combined resistance risk of QNs showed medium risk level (0.1

Occurrence, distribution, and risk assessment of quinolone antibiotics in municipal sewage sludges throughout China.

A nationwide study of the occurrence, distribution, potential drivers, and ecological risks of 24 quinolone antibiotics (QNs) in 74 Chinese sludge samples from 48 wastewater treatment plants (WWTPs) was conducted. In domestic sludge, the ∑QNs concentrations were  3rd-generation QNs > 4th-generation QNs > 1st-generation QNs. Meanwhile, abundant veterinary and human/veterinary quinolones (

Occurrence profiling and environmental risk assessment of veterinary antibiotics in vegetable soils at Chongqing region, China.

Veterinary antibiotics (VAs) are emerging contaminants in soils as they may pose high risks to the ecosystem and human health. Identifying VAs accumulation in soils is essential for assessing their potential risks. Therefore, we investigated the distribution of VAs in soils from vegetable fields and evaluated their potential ecological and antimicrobial resistance risks in the Chongqing region of the Three Gorges Reservoir area, China. Results indicated that twenty-six species of VAs, including nine sulfonamides (SAs), seven quinolones (QNs), four tetracyclines (TCs), four macrolides (MLs), and two other species of VAs were detected in soils, with their accumulative levels ranging from 1.4 to 3145.7 µg kg-1. TCs and QNs were the dominant VAs species in soils with high detection frequencies (100% TCs and 80.6% for QNs) and accumulative concentration (up to 1195 µg kg-1 for TCs and up to 485 µg kg-1 for QNs). Risk assessment indices showed that VAs (specifically SAs, TCs, and QNs) in most vegetable soils would pose a medium to high risk to the ecosystem and antimicrobial resistance. Mixture of VAs posed a higher risk to soil organisms, antimicrobial resistance, and plants than to aquatic organisms. Modeling analysis indicated that socioeconomic conditions, farmers' education levels, agricultural practices, and soil properties were the main factors governing VAs accumulation and environmental risks. Farmers with a high educational level owned large-scale farms and were more willing to use organic fertilizers for vegetable production, which eventually led to high VAs accumulation in vegetable soil. These findings would provide a reference for sustainable agricultural and environmental production under the current scenario of chemical fertilizer substitution by organic products and green agricultural development.

Estimating the effect of increasing ambient temperature on antimicrobial resistance in China: A nationwide ecological study with the difference-in-differences approach.

Antimicrobial resistance (AMR) and the possible consequences of rising ambient temperatures brought on by global warming have been extensively discussed. However, the epidemiological evidence on the effects of temperature on AMR is rare and little is known about the role of socioeconomic inequities. This ecological study obtained 31 provinces AMR data of Escherichia Coli (E. coli) from the China Antimicrobial Resistance Surveillance System (CARSS) over the period from 2014 to 2020, which were linked to the meteorological and socioeconomic data published in the China Statistical Yearbook. Modified difference-in-differences (DID) analyses were performed to estimate the effect of ambient temperature on AMR of E. coli to third-generation cephalosporins (ceftriaxone and cefotaxime), carbapenems, and quinolones, adjusting for variations in meteorological and socioeconomic factors. We estimated that every 1 °C increase in average ambient temperature was associated with 2.71 % (95 % confidence interval [CI]: 1.20-4.24), 32.92 % (95 % CI: 15.62-52.81), and 1.81 % (95 % CI: 0.47-3.16) increase in the prevalence of E. coli resistance to third-generation cephalosporins (ceftriaxone and cefotaxime), carbapenems and quinolones, respectively. The link was more profound in the regions with lower temperature and a median level of average humidity, and the regions with lower income, lower expenditure (in economics), lower health resources, and lower hospital admissions. Neither the replacement of the temperature variable nor the alternative approaches for confounding adjustment changed the positive association between ambient temperature and AMR. In general, there exists a positive association between ambient temperature and AMR, although the strength of such an association varies by socioeconomic and health services factors. The association is possibly nonlinear, especially for E. coli resistance to third-generation cephalosporins. The findings suggest that AMR control programs should explicitly incorporate weather patterns to increase their effectiveness.

Occurrence, source apportionment and ecological risk assessment of thirty antibiotics in farmland system.

Antibiotics are widely used in medical care, livestock production, and aquaculture. However, antibiotic pollution has attracted increasing global concerns due to their ecological risks after entering into environmental ecosystem via animal excretion, effulent from industrial and domestic sewage treatment facilities. In this study, 30 antibiotics were investigated in soils and irrigation rivers using ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometer. This study evaluated the occurrence, source apportionment, and ecological risks of these target compounds in soils and irrigation rivers (i.e., sediments and water) of farmland system by using principal component analysis-multivariate linear regression (PCA-MLR) and risk quotients (RQ). The concentration range of antibiotics in soils, sediments, and water was 0.38-689.58 ng/g, 81.99-658.00 ng/g, and 134.45-1547.06 ng/L, respectively. In soils, the most abundant antibiotics were quinolones and antifungals with an average concentration of 30.00 ng/g and 7.69 ng/g, respectively, contributing to 40% of total antibiotics. Macrolides were the most frequently detected antibiotics in soils with an average concentration of 4.94 ng/g. In irrigation rivers, quinolones and tetracyclines, the most abundant antibiotics, accounted for 78% and 65% of antibiotics in water and sediments, respectively. Higher antibiotic contamination of irrigation water was primarily distributed in highly populated urban areas, while increasing antibiotic contamination of sediments and soils was particularly observed in rural areas. PCA-MLR analysis indicated that antibiotic contamination in soils was mainly ascribed to the irrigation of sewage-receiving water body and manure application of livestock and poultry farming, which cumulatively contributed to 76% of antibiotics. According to RQ assessment, quinolones in irrigation rivers posed high risk to algae and daphnia, contributing 85% and 72% to the mixture risk, respectively. In soils, macrolides, quinolones and sulfonamides were responsible for more than 90% to the mixture risk of antibiotics. Ultimately, these findings can improve our fundamental knowledge on contamination characteristics and source pathways towards risk management of antibiotics in farmland system.

Assessment and validation of the p-QuEChERS sample preparation methodology for the analysis of >200 veterinary drugs in various animal-based food matrices.

The need remains for veterinary multi-residue methods that reliably quantify and identify veterinary drugs in the various animal-based food matrices. Such a method should not only show good method performance parameters (e.g. recoveries of analytes) but must also be fast and cheap. The proposed method focused on the following points: acceptable analyte trueness (recovery) and precision for a large number (200) of diverse veterinary drugs in the relevant animal-based food matrices (egg, muscle, fatty fish, liver, kidney, and honey). The sample preparation method termed p-QuEChERS uses a salt mixture consisting of potassium phosphates to induce phase separation. The avoidance of conventional QuEChERS salts (e.g. magnesium sulphate) significantly improves recoveries of several critical analytes. Analyte recoveries were further improved by adding a centrifugation and a defatting step before initiating the salt-induced phase separation. This combined clean-up removes a large fraction of the potentially interfering matrix compounds. As a result, matrix effects in the electrospray interface were minimized. These factors were the basis for the obtained good validation data. Two types of high-resolution mass spectrometers coupled to liquid chromatography were compared for analysis. In comparison with conventional QuEChERS, the proposed p-QuEChERS concept improved the recovery of polar analytes such as penicillins, tetracyclines and quinolones. The simplicity of the procedure and the low consumable expenses make the method ideal for the routine control of veterinary drugs in all evaluated animal-based food matrices.

Characterisation of burden of illness measures associated with human (Fluoro)quinolone-resistant Campylobacter spp. infections - a scoping review.

Campylobacter spp. are one of the most common causes of bacterial gastroenteritis in Canada and worldwide. Fluoroquinolones are often used to treat complicated human campylobacteriosis and strains of Campylobacter spp. resistant to these drugs are emerging along the food chain. A scoping review was conducted to summarise how human (fluoro)quinolone-resistant (FQR; quinolones including fluoroquinolones) Campylobacter spp. infections are characterised in the literature by describing how burden of illness (BOI) associated with FQR is measured and reported, describing the variability in reporting of study characteristics, and providing a narrative review of literature that compare BOI measures of FQR Campylobacter spp. infections to those with susceptible infections. The review identified 26 studies that yielded many case reports, a lack of recent literature and a lack of Canadian data. Studies reported 26 different BOI measures and the most common were hospitalisation, diarrhoea, fever and duration of illness. There were mixed results as BOI measures reported in literature were inconsistently defined and there were limited comparisons between resistant and susceptible infections. This presents a challenge when attempting to assess the magnitude of the BOI due to FQR Campylobacter spp., highlighting the need for more research in this area.

Assessment of heterocyclic aromatic amines contents in flamed and braised chicken in Burkina Faso.

The nutritional status of meat is tarnished by its association with the induced cooking contaminants. The aim of this study was to assess the heterocyclic aromatic amines profile and contents in processed chicken in Burkina Faso. Eight polar and apolar heterocyclic aromatic amines (HAAs) including 2-mino-3-methylimidazo[4,5-f]quinolone (IQ), 3-amino-1,4-dimethyl-5H-pyrido[4, 3-b]indole (Trp-P1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P2), 2-mino-9H-pyrido-[2,3-b]indole (AαC), 2-amino-1-methyl-6-phenylimidazo[4, 5- ]pyridine (PhIP), 2-amino-3-methyl-9H-pyrido[2,3-b] indole (MeAαC), 2-amino-3,4,8-rimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-amino-3,8-imethylimidazo[4,5-]quinoxaline (MeIQx) were screened by high performance liquid chromatography from 29 samples of flamed chicken and 66 samples of braised chicken collected in Ouagadougou city. Apolar HAAs and polar HAAs were respectively 12 and 3 times more abundant in flamed chickens (32.66±10 and 3.48±10.39 ng/g, respectively) than in braised chickens (2.70±9.67 and 0.92 ng/g, respectively). The maximum levels of AαC were in the same proportions in flamed (12.01 ng/g) and braised chickens (14.13 ng/g). Flamed chicken had the highest Trp-P1 content (530.31 ng/g). The 4,8-DiMeIQx was not detected in braised chicken. The AαCs were more abundant in flamed than in braised chicken. The profile and the contents of the HAAs in processed chicken are related to cooking methods. Because of the high variability observed on the obtained concentrations, investigations on the contents of precursors in raw chicken, the effect of marinating ingredients on the formation of HAAs are needed.

[Pollution Characteristics and Ecological Risk Assessment of Antibiotics in Vegetable Field in Kaizhou, Chongqing].

The accumulation of antibiotics in farmland and its ecological risk have become a research hotspot at home and abroad. The objective of this study was to investigate the occurrence and accumulation of antibiotics and their potential environmental and ecological risks in vegetable fields in Kaizhou district of Chongqing country. The occurrence characteristics of antibiotics including tetracyclines, sulfonamides, quinolones, macrolides, and chloramphenicols were detected using experimental analysis. The results showed that there was an accumulation of antibiotics in the vegetable soil, and 18 antibiotics in five categories were detected (0-42.88 µg·kg-1), mainly for tetracyclines and quinolones. The detection rate of quinolone antibiotics was the highest (15.38%-100%), especially for norfloxacin and ofloxacin (100%), whereas the tetracyclines presented the highest concentration (0-42.88 µg·kg-1). The amount of total antibiotics in the vegetable soil was 1.64-233.11 µg·kg-1, whereas different vegetable soils showed the following trend:water spinach soil (89.73 µg·kg-1)>cabbage soil (32.53 µg·kg-1)>pepper soil (32.16 µg·kg-1)>tomato soil (32.13 µg·kg-1)>cucumber soil (26.46 µg·kg-1)>grassland (7.32 µg·kg-1). The correlation results showed that there was a significantly positive correlation between total antibiotic residues and organic fertilizer application (P<0.05) but a significantly negative correlation with soil pH (P<0.05). Quinolones and sulfonamides were negatively correlated with soil water content (P<0.05), whereas quinolones positively correlated with soil available phosphorus and organic matter content (P<0.05). The potential eco-environmental risk assessment results showed that tetracyclines and quinolones in vegetable soil in Kaizhou district had certain ecological risks, of which 62%-92% and 62%-100% of soil samples with quinolones had potential toxicity to soil animals and microorganisms.

Accumulation and risk assessment of antibiotics in edible plants grown in contaminated farmlands: A review.

The extensive occurrence of antibiotics in farmland soil might threaten food safety. The bioaccumulation potential of antibiotics in edible vegetables and crops grown under realistic farming scenarios was reviewed and the human health risk was assessed. A total of 51 antibiotics were documented in 37 species of daily consumed crops. Among different classes of antibiotics, tetracyclines (TCs) exhibited higher residue levels in plants than quinolones (QNs), sulfonamides (SAs), and macrolides (MLs), with median values ranging from 5.10 to 15.4 µg/kg dry weight. The favored accumulation of TCs in plants was probably linked to their relatively higher residual concentrations in soils and greater bioconcentration factors. Compared with the plants grown in open field, accumulation of antibiotics was higher in plant grown under greenhouse condition, probably due to the higher residue levels of antibiotics in the greenhouse soil with intensive application of manure. Cocktails of antibiotics were investigated in potato, corn, carrot, tomato, lettuce, and wheat. Among them, corn exhibited relatively high median concentrations of antibiotics (0.400-203 µg/kg dry weight). Antibiotics tended to accumulate in plant root and their concentrations in fruit were generally low. Risk assessment revealed that human health risk was under the alert line through the daily consumption of antibiotic contaminated vegetables and food crops.

[Ecological Risk Assessment of Quinolones Antibiotics and the Correlation Analysis Between QNs and Physical-Chemical Parameters in Groundwater, Shijiazhuang City].

Most studies on antibiotics in groundwater have focused on pollution characteristics, whereas less attention has been paid to the ecological risks of antibiotics and the correlation to environmental parameters. In this study, the groundwater in Shijiazhuang City was selected as the research area. Through high performance liquid chromatography-tandem mass spectrometry (HPLC-MS), the concentration of quinolones (QNs) in the groundwater was analyzed. Correlation analysis was conducted between QNs concentrations and physical-chemical parameters. The results showed that:① the detection frequency of flumequine (FLU) was the highest (100%), followed by enoxacin (ENO) (80.0%) and ciprofloxacin (CIP) (75.0%). ② The concentration of QNs ranged from 3.02 to 98.5 ng·L-1; in terms of spatial distribution, the highest concentration of QNs appeared at S4 (98.5 ng·L-1), whereas the lowest concentration was exhibited at S19 (3.02 ng·L-1). ③ Temperature (T), chemical oxygen demand (COD), total dissolved solids (TDS), total number of colonies (BCTC), and pH were significantly correlated with QNs (P<0.01 or P<0.05) based on correlation analysis. ④ For the spatial distribution of ecological risk, the results showed that the ecological risk at S4 was high, whereas the risks for other sites were low. For the type of QNs, ciprofloxacin (CIP) was at a medium-high risk level, whereas the other QNs were at a low-risk level. Thus, in order to guarantee the ecological safety of groundwater in Shijiazhuang City, more attention should be paid to the risk management and control of antibiotics in groundwater in the future.