The development of an integrated environment-human risk approach for the prioritisation of antibiotics for policy decisions.

Environmental contamination with antibiotic residues has caused significant concern. Antibiotics are continually emitted into the environment which potentially threatens environmental and human health, particularly, the risk in the development of antibiotic resistance. A list of priority antibiotics in the environment is essential for eco-pharmacovigilance and policy decisions. This study developed a prioritisation system of antibiotics based on their integrated environmental (resistance and ecotoxicity) and human health (resistance and toxicity) risks, considering various aquatic environmental compartments. Data obtained by conducting a systematic review of the literature of antibiotic residues in various aquatic environmental compartments in China was used as an example. The list of priority antibiotics was created by ranking the antibiotics in descending order, based on the risk scores of their a) overall risk, (b) antibiotic resistance risk to environment, (c) ecotoxicity risk, (d) overall environmental risk, (e) antibiotic resistance risk to human health, (f) toxicity risk to human health and (g) overall human health risk. Ciprofloxacin posed the greatest risk and chloramphenicol posed the least risk. The output from this research can be used to implement eco-pharmacovigilance and to develop targeted policies which would prevent / minimise the environmental and human health risks from antibiotic residues. The use of this list of priority antibiotics will allow for a country / region / setting to (a) optimise the use of antibiotics and their prescribing practices, (b) create effective monitoring and mitigation strategies, (c) minimise the discharge of antibiotic residues and (d) focus research efforts.

Antibiotic concentrations and antibiotic resistance in aquatic environments of the WHO Western Pacific and South-East Asia regions: a systematic review and probabilistic environmental hazard assessment.

BACKGROUND: Antibiotic resistance poses human health risks, and there are concerns about the effect of environmental antibiotic residues in the selection and spread of antibiotic resistance. The aim of this study was to identify antibiotic residue levels that are likely to select for resistance and relative contributions from different aquatic sources, of various aquatic environmental compartments of the WHO Western Pacific region (WPR) and the WHO South-East Asia region (SEAR), including in China and India. METHODS: A systematic review of empirical studies that measured antibiotic concentrations in aquatic environments, published between 2006 and 2019, and a probabilistic environmental hazard assessments approach, were used to identify antibiotic concentrations that are likely to select for resistance in various aquatic environmental compartments of the WPR and SEAR, including in China and India. The assessment involved the use of measured environmental concentrations and predicted no-effect concentrations (PNECs). FINDINGS: The systematic review found 218 relevant studies of 5230 screened from the WPR and 22 relevant studies of 2625 screened from the SEAR; some of these relevant studies were largely from China (n=168) and India (n=15). 92 antibiotics in the WPR and 45 in the SEAR were detected in various aquatic compartments. Antibiotic concentrations that most likely exceeded PNECs (0-100%) were observed in wastewater, and influents and effluents of wastewater treatment plants. Antibiotic concentrations that most likely exceeded PNECs were also observed in aquatic environmental compartments. The highest risk for the development of resistance was in tap or drinking water of the WPR and China for ciprofloxacin (62·5%). The relative contributions of potential sources of antibiotic contamination in waterways, such as hospitals, municipals, livestock, and pharmaceutical manufacturing, was determined for each antibiotic. INTERPRETATION: The concentrations of antibiotic residues found in wastewater and wastewater treatment plants of the WPR and SEAR make them potential hotspots for the development of antibiotic resistance, which creates human health risks from environmental exposure via drinking water. These findings can help decision makers to target risk reduction measures against environmental residues of priority antibiotics in high-risk sites, and help to focus research efforts in these world regions. FUNDING: Swedish Research Council.

Monitoring of Water Quality, Antibiotic Residues, and Antibiotic-Resistant Escherichiacoli in the Kshipra River in India over a 3-Year Period.

The emergence of antibiotic resistance is a major global and environmental health issue, yet the presence of antibiotic residues and resistance in the water and sediment of a river subjected to excessive anthropogenic activities and their relationship with water quality of the river are not well studied. The objectives of the present study were a) to investigate the occurrence of antibiotic residues and antibiotic-resistant Escherichiacoli (E.coli) in the water and sediment of the Kshipra river in India at seven selected sites during different seasons of the years 2014, 2015, and 2016 and b) to investigate the association between antibiotic residues and antibiotic-resistant E.coli in water and sediment and measured water quality parameters of the river. Antibiotic residues and resistant E.coli were present in the water and sediment and were associated with the measured water quality parameters. Sulfamethoxazole was the most frequently detected antibiotic in water at the highest concentration of 4.66 µg/L and was positively correlated with the water quality parameters. Significant (p < 0.05) seasonal and spatial variations of antibiotic-resistant E.coli in water and sediment were found. The resistance of E.coli to antibiotics (e.g., sulfamethiazole, norfloxacin, ciprofloxacine, cefotaxime, co-trimoxazole, ceftazidime, meropenem, ampicillin, amikacin, metronidazole, tetracycline, and tigecycline) had varying associations with the measured water and sediment quality parameters. Based on the results of this study, it is suggested that regular monitoring and surveillance of water quality, including antibiotic residues and antibiotic resistance, of all rivers should be taken up as a key priority, in national and Global Action Plans as these can have implications for the buildup of antibiotic resistance.

Seasonal Variations in Water-Quality, Antibiotic Residues, Resistant Bacteria and Antibiotic Resistance Genes of Escherichia coli Isolates from Water and Sediments of the Kshipra River in Central India.

OBJECTIVES: To characterize the seasonal variation, over one year, in water-quality, antibiotic residue levels, antibiotic resistance genes and antibiotic resistance in Escherichia coli isolates from water and sediment of the Kshipra River in Central India. METHODS: Water and sediment samples were collected from seven selected points from the Kshipra River in the Indian city of Ujjain in the summer, rainy season, autumn and winter seasons in 2014. Water quality parameters (physical, chemical and microbiological) were analyzed using standard methods. High-performance liquid chromatography⁻tandem mass spectrometry was used to determine the concentrations of antibiotic residues. In river water and sediment samples, antibiotic resistance and multidrug resistance patterns of isolated E. coli to 17 antibiotics were tested and genes coding for resistance and phylogenetic groups were detected using multiplex polymerase chain reaction. One-way analysis of variance (ANOVA) and Fisher tests were applied to determine seasonal variation. RESULTS: In river water, seasonal variation was significantly associated with various water quality parameters, presence of sulfamethoxazole residues, bacteria resistant to ampicillin, cefepime, meropenem, amikacin, gentamicin, tigecycline, multidrug resistance and CTX-M-1 gene. The majority of the Extended Spectrum Beta-Lactamase (ESBL)-producing E. coli isolates from river water and sediment in all different seasons belonged to phylogenetic group A or B1. CONCLUSIONS: Antibiotic pollution, resistance and resistance genes in the Kshipra River showed significant seasonal variation. Guidelines and regulatory standards are needed to control environmental dissemination of these “pollutants” in this holy river.

Presence of antibiotic residues in various environmental compartments of Shandong province in eastern China: Its potential for resistance development and ecological and human risk.

OBJECTIVES: To investigate the occurrence of antibiotic residues in different types of environmental samples including water samples in rural Shandong province, China. Further, to characterize the potential ecological risk for development of antibiotic resistance in the environment, and the potential direct human health risk of exposure to antibiotics via drinking water and vegetables. METHODS: Environmental samples (n = 214) (river water, waste water, drinking water, sediments, manure, soil and edible parts of vegetables) were collected in twelve villages in Shandong province in eastern China. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to determine the concentration of antibiotic residues. The ratio of the measured environmental concentrations (MEC) to the predicted no-effect concentrations (PNEC) was used to evaluate the ecological risk (risk quotient, RQ) for development of antibiotic resistance. The potential risks to human health through exposure to antibiotics in drinking water were assessed by comparing measured environmental concentrations (MEC) and predicted no-effect concentration in drinking water (PNECDW), and in vegetables by comparing estimated daily intake (EDI) to ADI. RESULTS: Sulfapyridine, sulfamethoxazole, ciprofloxacin, enrofloxacin, levofloxacin, norfloxacin, chloramphenicol, florfenicol, doxycycline, and metronidazole were detected at concentrations ranging between 0.3 and 3.9 ng/L in river water, 1.3 and 12.5 ng/L in waste water, 0.5 and 21.4 ng/L in drinking water, 0.31 and 1.21 µg/kg in river sediment, 0.82 and 1.91 µg/kg in pig manure, 0.1 and 11.68 µg/kg in outlet sediment, 0.5 and 2.5 µg/kg in soil, and 6.3 and 27.2 µg/kg in vegetables. The RQs for resistance development were >1 for enrofloxacin, levofloxacin, and ranged between 0.1 and 1 for ciprofloxacin. MECs/PNECDW ratios were <1 from exposure to antibiotics through drinking water for both adults and children. EDI/ADI ratios were <0.1 from exposure to antibiotics by vegetable consumption. CONCLUSIONS: Antibiotic pollutants were ubiquitous in various environmental compartments of Shandong province of China. Risk estimates indicated a potential for the measured levels of enrofloxacin, levofloxacin and ciprofloxacin in waste water to pose an ecological risk for resistance selection, and further studies are needed to validate this finding. The investigated antibiotics did not appear to pose an appreciable direct human health risk from environmental exposure through drinking water or vegetables consumption. However, they might still pose a risk for resistance development.

Vowel identification by cochlear implant users: contributions of static and dynamic spectral cues.

Previous research has shown that normal hearing listeners can identify vowels in syllables on the basis of either quasi-static or dynamic spectral cues; however, it is not known how well cochlear implant (CI) users with current-generation devices can make use of these cues. The present study assessed vowel identification in adult CI users and a comparison group of young normal hearing (YNH) listeners. Stimuli were naturally spoken /dVd/ syllables and modified syllables that retained only quasi-static spectral cues from an 80-ms segment of the vowel center ("C80" stimuli) or dynamic spectral cues from two 20-ms segments of the vowel edges ("E20" stimuli). YNH listeners exhibited near-perfect performance for the unmodified (99.8%) and C80 (92.9%) stimuli and maintained good performance for the E20 stimuli (70.2%). CI users exhibited poorer average performance than YNH listeners for the Full stimuli (72.3%) and proportionally larger reductions in performance for the C80 stimuli (41.8%) and E20 stimuli (29.0%). Findings suggest that CI users have difficulty identifying vowels on the basis of spectral cues in the absence of duration cues, and have limited access to brief dynamic spectral cues. Error analyses suggest that CI users may rely strongly on vowel duration cues when those cues are available.