| 1. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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Concentrations of antibiotics predicted to select for resistant bacteria: Proposed limits for environmental regulation
- 2016
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 86, s. 140-149
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Tidskriftsartikel (refereegranskat)abstract
- There are concerns that selection pressure from antibiotics in the environment may accelerate the evolution and dissemination of antibiotic-resistant pathogens. Nevertheless, there is currently no regulatory system that takes such risks into account. In part, this is due to limited knowledge of environmental concentrations that might exert selection for resistant bacteria. To experimentally determine minimal selective concentrations in complex microbial ecosystems for all antibiotics would involve considerable effort. In this work, our aim was to estimate upper boundaries for selective concentrations for all common antibiotics, based on the assumption that selective concentrations a priori need to be lower than those completely inhibiting growth. Data on Minimal Inhibitory Concentrations (MICs) were obtained for 111 antibiotics from the public EUCAST database. The 1% lowest observed MICs were identified, and to compensate for limited species coverage, predicted lowest MICs adjusted for the number of tested species were extrapolated through modeling. Predicted No Effect Concentrations (PNECs) for resistance selection were then assessed using an assessment factor of 10 to account for differences between MICs and minimal selective concentrations. The resulting PNECs ranged from 8 ng/L to 64 μg/L. Furthermore, the link between taxonomic similarity between species and lowest MIC was weak. This work provides estimated upper boundaries for selective concentrations (lowest MICs) and PNECs for resistance selection for all common antibiotics. In most cases, PNECs for selection of resistance were below available PNECs for ecotoxicological effects. The generated PNECs can guide implementation of compound-specific emission limits that take into account risks for resistance promotion.
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| 2. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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Protection goals must guide risk assessment for antibiotics
- 2018
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Ingår i: Environment international. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 111, s. 352-353
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Tidskriftsartikel (refereegranskat)abstract
- In a recent paper published in Environment International, Le Page et al. (2017) stress that discharge limits for antibiotics need to consider their potency to affect both environmental and human health, a very sound standpoint also from our point of view. It is reasoned that predicted no-effect concentrations for resistance selection (PNECs) derived from the minimal inhibitory concentrations (MICs) of the most sensitive studied human-associated bacteria (Bengtsson-Palme and Larsson, 2016a), may not be sufficiently protective as environmental cyanobacteria in many cases appear to be more sensitive, according to the authors. The antibiotic resistance health crisis, and the growing understanding of the contribution of the environment in this development, indicates an urgent need for discharge limits for antibiotics, particularly for industrial sources (Bengtsson-Palme and Larsson, 2016b). Such limits would have tremendous value in regulation efforts (Government of India, 2017), for initiatives from the industry themselves (IFPMA, 2016), and for development of environmental criteria within public procurement and generic exchange programs (Bengtsson-Palme et al., 2018; Laurell et al., 2014; SPHS Secreteriat, UNDP Istanbul Regional Hub, 2015). However, somewhat in contrast to what the authors conclude, we do not think there is evidence that cyanobacteria would often be more sensitive to antibiotics than the most sensitive human-associated bacteria. Importantly, we also think that it is a bit unclear from the paper which protection goals are considered (protecting microbial diversity in ecosystems, protecting ecosystem functions and services, or protecting from risks for resistance selection) and particularly in what ways ecotoxicological test data could inform each of these targets.
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| 3. |
- Huijbers, Patricia, 1985, et al.
(författare)
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A conceptual framework for the environmental surveillance of antibiotics and antibiotic resistance.
- 2019
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Ingår i: Environment international. - : Elsevier BV. - 1873-6750 .- 0160-4120. ; 130
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Tidskriftsartikel (refereegranskat)abstract
- Environmental surveillance of antibiotics and antibiotic resistance could contribute toward the protection of human, animal and ecosystem health. However, justification for the choice of markers and sampling sites that informs about different risk scenarios is often lacking. Here, we define five fundamentally different objectives for surveillance of antibiotics and antibiotic resistance in the environment. The first objective is (1) to address the risk of transmission of already antibiotic-resistant bacteria to humans via environmental routes. The second is (2) to address the risk for accelerating the evolution of antibiotic resistance in pathogens through pollution with selective agents and bacteria of human or animal origin. The third objective is (3) to address the risks antibiotics pose for aquatic and terrestrial ecosystem health, including the effects on ecosystem functions and services. The two final objectives overlap with those of traditional clinical surveillance, namely, to identify (4) the population-level resistance prevalence and (5) population-level antibiotic use. The latter two environmental surveillance objectives have particular potential in countries where traditional clinical surveillance data and antibiotic consumption data are scarce or absent. For each objective, the levels of evidence provided by different phenotypic and genotypic microbial surveillance markers, as well as antibiotic residues, are discussed and evaluated on a conceptual level. Furthermore, sites where monitoring would be particularly informative are identified. The proposed framework could be one of the starting points for guiding environmental monitoring and surveillance of antibiotics and antibiotic resistance on various spatiotemporal scales, as well as for harmonizing such activities with existing human and animal surveillance systems.
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| 4. |
- Kraupner, Nadine, et al.
(författare)
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Selective concentration for ciprofloxacin resistance in Escherichia coli grown in complex aquatic bacterial biofilms
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 116, s. 255-268
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Tidskriftsartikel (refereegranskat)abstract
- There is concern that antibiotics in the environment can select for and enrich bacteria carrying acquired antibiotic resistance genes, thus increasing the potential of those genes to emerge in a clinical context. A critical question for understanding and managing such risks is what levels of antibiotics are needed to select for resistance in complex bacterial communities. Here, we address this question by examining the phenotypic and genotypic profiles of aquatic communities exposed to ciprofloxacin, also evaluating the within-species selection of resistant E. coli in complex communities. The taxonomic composition was significantly altered at ciprofloxacin exposure concentrations down to 1 μg/L. Shotgun metagenomic analysis indicated that mobile quinolone resistance determinants (qnrD, qnrS and qnrB) were enriched as a direct consequence of ciprofloxacin exposure from 1 μg/L or higher. Only at 5–10 μg/L resistant E.coli increased relative to their sensitive counterparts. These resistant E. coli predominantly harbored non-transferrable, chromosomal triple mutations (gyrA S83 L, D87N and parC S80I), which confer high-level resistance. In a controlled experimental setup such as this, we interpret effects on taxonomic composition and enrichment of mobile quinolone resistance genes as relevant indicators of risk. Hence, the lowest observed effect concentration for resistance selection in complex communities by ciprofloxacin was 1 μg/L and the corresponding no observed effect concentration 0.1 μg/L. These findings can be used to define and implement discharge or surface water limits to reduce risks for selection of antibiotic resistance in the environment. © 2018 Elsevier Ltd
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| 5. |
- Larsson, D. G. Joakim, 1969, et al.
(författare)
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Critical knowledge gaps and research needs related to the environmental dimensions of antibiotic resistance
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 117, s. 132-138
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Forskningsöversikt (refereegranskat)abstract
- There is growing understanding that the environment plays an important role both in the transmission of antibiotic resistant pathogens and in their evolution. Accordingly, researchers and stakeholders world-wide seek to further explore the mechanisms and drivers involved, quantify risks and identify suitable interventions. There is a clear value in establishing research needs and coordinating efforts within and across nations in order to best tackle this global challenge. At an international workshop in late September 2017, scientists from 14 countries with expertise on the environmental dimensions of antibiotic resistance gathered to define critical knowledge gaps. Four key areas were identified where research is urgently needed: 1) the relative contributions of different sources of antibiotics and antibiotic resistant bacteria into the environment; 2) the role of the environment, and particularly anthropogenic inputs, in the evolution of resistance; 3) the overall human and animal health impacts caused by exposure to environmental resistant bacteria; and 4) the efficacy and feasibility of different technological, social, economic and behavioral interventions to mitigate environmental antibiotic resistance.(1)
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| 6. |
- Marathe, Nachiket, et al.
(författare)
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Functional metagenomics reveals a novel carbapenem-hydrolyzing mobile beta-lactamase from Indian river sediments contaminated with antibiotic production waste
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 112, s. 279-286
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Elsevier Ltd Evolution has provided environmental bacteria with a plethora of genes that give resistance to antibiotic compounds. Under anthropogenic selection pressures, some of these genes are believed to be recruited over time into pathogens by horizontal gene transfer. River sediment polluted with fluoroquinolones and other drugs discharged from bulk drug production in India constitute an environment with unprecedented, long-term antibiotic selection pressures. It is therefore plausible that previously unknown resistance genes have evolved and/or are promoted here. In order to search for novel resistance genes, we therefore analyzed such river sediments by a functional metagenomics approach. DNA fragments providing resistance to different antibiotics in E. coli were sequenced using Sanger and PacBio RSII platforms. We recaptured the majority of known antibiotic resistance genes previously identified by open shot-gun metagenomics sequencing of the same samples. In addition, seven novel resistance gene candidates (six beta-lactamases and one amikacin resistance gene) were identified. Two class A beta-lactamases, bla RSA1 and bla RSA2 , were phylogenetically close to clinically important ESBLs like bla GES , bla BEL and bla L2 , and were further characterized for their substrate spectra. The blaRSA1 protein, encoded as an integron gene cassette, efficiently hydrolysed penicillins, first generation cephalosporins and cefotaxime, while blaRSA2 was an inducible class A beta-lactamase, capable of hydrolyzing carbapenems albeit with limited efficiency, similar to the L2 beta-lactamase from Stenotrophomonas maltophilia. All detected novel genes were associated with plasmid mobilization proteins, integrons, and/or other resistance genes, suggesting a potential for mobility. This study provides insight into a resistome shaped by an exceptionally strong and long-term antibiotic selection pressure. An improved knowledge of mobilized resistance factors in the external environment may make us better prepared for the resistance challenges that we may face in clinics in the future.
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