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Background: Emissions of high concentrations of antibiotics from manufacturing sites select for resistant bacteria and may contribute to the emergence of new forms of resistance in pathogens. Many scientists, industry, policy makers and other stakeholders recognize such pollution as an unnecessary and unacceptable risk to global public health. An attempt to assess and reduce such discharges, however, quickly meets with complex realities that need to be understood to identify effective ways to move forward. This paper charts relevant key actor-types, their main stakes and interests, incentives that can motivate them to act to improve the situation, as well as disincentives that may undermine such motivation. Methods: The actor types and their respective interests have been identified using research literature, publicly available documents, websites, and the knowledge of the authors. Results: Thirty-three different actor-types were identified, representing e.g. commercial actors, public agencies, states and international institutions. These are in complex ways connected by interests that sometimes may conflict and sometimes pull in the same direction. Some actor types can act to create incentives and disincentives for others in this area. Conclusions: The analysis demonstrates and clarifies the challenges in addressing industrial emissions of antibiotics, notably the complexity of the relations between different types of actors, their international dependency and the need for transparency. The analysis however also suggests possible ways of initiating incentive-chains to eventually improve the prospects of motivating industry to reduce emissions. High-resource consumer states, especially in multinational cooperation, hold a key position to initiate such chains.
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R E S E A R C H Open Access
Managing pollution from antibiotics
manufacturing: charting actors, incentives
and disincentives
Niels Nijsingh
1,2,3
, Christian Munthe
1,2
and D. G. Joakim Larsson
1,4*
Abstract
Background: Emissions of high concentrations of antibiotics from manufacturing sites select for resistant bacteria
and may contribute to the emergence of new forms of resistance in pathogens. Many scientists, industry, policy
makers and other stakeholders recognize such pollution as an unnecessary and unacceptable risk to global public
health. An attempt to assess and reduce such discharges, however, quickly meets with complex realities that need
to be understood to identify effective ways to move forward. This paper charts relevant key actor-types, their main
stakes and interests, incentives that can motivate them to act to improve the situation, as well as disincentives that
may undermine such motivation.
Methods: The actor types and their respective interests have been identified using research literature, publicly
available documents, websites, and the knowledge of the authors.
Results: Thirty-three different actor-types were identified, representing e.g. commercial actors, public agencies,
states and international institutions. These are in complex ways connected by interests that sometimes may conflict
and sometimes pull in the same direction. Some actor types can act to create incentives and disincentives for
others in this area.
Conclusions: The analysis demonstrates and clarifies the challenges in addressing industrial emissions of antibiotics,
notably the complexity of the relations between different types of actors, their international dependency and the
need for transparency. The analysis however also suggests possible ways of initiating incentive-chains to eventually
improve the prospects of motivating industry to reduce emissions. High-resource consumer states, especially in
multinational cooperation, hold a key position to initiate such chains.
Keywords: Antimicrobial resistance; management, Environmental pollution, Policy
Background
Antibiotic resistance presents a serious and growing
threat to global health. Effective antibiotics constitute
not only our most important tool to treat bacterial infec-
tions, but are also critical for the effectiveness of many
other areas of modern healthcare [1]. Use, misuse and
overuse of antibiotics in humans and animals, together
with insufficient hygiene and infection control, are the
most important drivers of resistance on a global basis.
Since bacteria and bacterial genes often move through
the environment and across humans and animals [24],
aOne Healthperspective that takes all three of these
domains into account is essential [57]. The environ-
ment plays a role both in the transmission of resistant
pathogens and as a source for resistance factors that
over time are transferred horizontally to pathogens. In
both cases, antibiotics emitted into the environment cre-
ate a selection pressure likely to favour resistant strains
[8]. Antibiotic pollution occurs, partly, as a result of
excretion from humans and domestic animals. Although
widespread, it is still uncertain to what extent the levels
found from such sources select for resistant bacteria [9].
In contrast, antibiotic pollution due to wastewater
© The Author(s). 2019, corrected publication 2019. Open Access This article is distributed under the terms of the Creative
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provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
* Correspondence: joakim.larsson@fysiologi.gu.se
1
Centre for Antibiotic Resistance Research (CARe), at University of
Gothenburg, Gothenburg, Sweden
4
Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska
Academy, University of Gothenburg, Gothenburg, Sweden
Full list of author information is available at the end of the article
Nijsingh et al. Environmental Health (2019) 18:95
https://doi.org/10.1186/s12940-019-0531-1
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
emissions from manufacturing plants of antibiotics can
be staggering, with concentrations reaching into the mg/
L range, constituting strong drivers of resistance [10]. It
is therefore not surprising that there is increasing recog-
nition of the need for global coordinated action to
reduce industrial antibiotics emissions [4,1115].
This paper aims to contribute to the understanding
of institutional aspects that is necessary for evidence-
based and effective action in this area. We present a
map of actors, detailed in the Additional file 1,that
may facilitate more effective pollution control and
identification of what incentives or disincentives may
affect their tendency to act. On this basis, we also
address issues about sharing of key responsibilities for
initiating and sustaining effective measures to curb
industrial antibiotics pollution.
In the next section, we explain the theoretical back-
ground, the method we have used when completing
the map of actors and incentives, as well as the limi-
tations of our analysis. In the Results section, we use
the taxonomy provided in the Additional file 1and
suggestthatinansweringthequestiononwhoshould
act, we need to distinguish between consumerand
producercountries. By making this distinction, we
do not mean to imply that different countries are ex-
clusively producers or consumers of antibiotics, but
rather that in analysing the various (dis)incentives, we
need to distinguish between different roles of coun-
triesaseitherconsumerorproducer.Wethende-
scribe how actors in both antibiotic consumer and
producer countries can be motivated to effective ac-
tion (incentives), as well as factors that would hinder
such motivation (disincentives). In the Conclusions
section, we summarise the main findings, and expand
our analysis to discuss the distribution of responsi-
bilities among the actor types. We conclude that
high-income consumer states and certain public insti-
tutions within these are in a key position to initiate
effective change, especially through multinationally
coordinated actions.
Methods
Any attempt to initiate effective actions to reduce in-
dustrial antibiotic pollution has to face intricate real-
ities when trying to decide what actions should be
taken, and by whom. The production, trade and
consumption chain of pharmaceuticals is complex and
involves many actors with different interests. The chal-
lenge therefore needs to be approached from a complex
system perspective [16]. When considering the costs
and benefits of various interventions on specific levels
and within specific sectors, we need to also consider
how different levels and sectors may interact to either
favour or undermine better pollution control. The
interdependencies within and between systems and
parts of systems of different acting parties therefore
need to be understood. This paper aims to take a first
step of contributing to such understanding by present-
ing a map of the relevant types of actors with their
respective interests, and describe possible incentives as
well as disincentives (some of which already exist, while
others may emerge due to policy choices).
The are several proposals in the literature on how to
address antibiotics pollution [3,1015,1720]. Despite
providing important contributions, all of the above
focus on individual drivers and actors, leaving the sys-
temic perspective largely unexplored. A map of actors
and their relations could therefore provide a clearer
insight into the ways in which these as well as future
proposals may interact and function. The primary
intention of the present study is not to argue for or
against specific interventions, but to analyse how differ-
ent types of actions may either support and enhance, or
come apart, conflict with or even undermine each
other. This will provide some general lines along which
actions might be designed and evaluated, and which
actors should be thought of as responsible for initiating
and sustaining such developments.
Besides peer-reviewed scientific literature, our material
has included governmental and corporate websites and
policy documents. We thereby identified 33 types of ac-
tors, and sorted these into a relational network that illus-
trates the actorsmain interests, and how they may
interact at and in between various levels (local, regional,
national, international) in light of these interests. On this
basis, we then inventoried the ways in which these actors
may be incentivized to act, including regulatory,
economic and political incentives.
In doing so, we make no particular assumptions about
the underlying motivational patterns of human beings.
Specifically, we do not presuppose a rational choice the-
ory nor do we presume that actors are only driven by
self-interest, but do assume that institutions act in con-
sideration of the charters, formal aims, and so on, which
define and direct them. By focusing on (dis)incentives,
we do not mean to deny that actors may be driven by a
variety of concerns, among which genuine worries on
the development of antibiotic resistance. However, we
also do not presume that merely presenting either indi-
vidual or institutional actors with evidence will be suffi-
cient to prompt them to do what is right from a moral
perspective or what desirable from a social perspective:
sometimes people need a push to do the right thing. It is
an empirical observation that people are often prone to
prioritise their short-term interests, which makes
pushing the right buttons in the form of incentives of
eminent importance in addressing complex, global prob-
lems, such as antibiotic pollution. For institutions, such
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as public agencies and corporations, there is a parallel
need to have actions match or adapt to legally mandated
goals (such as maximizing shareholder value for limited
companies), formal charters and surrounding regulation.
In our analysis, we put to one side driving forces that
are not specifically related to properties of the de-
scribed actors and therefore common to all or many of
them, such as inherent tendencies of institutions to
work in line with the motivation of their individual
employees [21].
The criterion for including actors was that doing so
would add to the understanding of how the different in-
centives and disincentives may come apart or together
in relation to the aim of controlling industrial antibiotics
pollution. Therefore, we have included a wide set of
actor types, but did not distinguish between single actors
motivated by very similar types of interests, as these are
prone to be motivated by the same type of incentives.
For instance, we do not distinguish between different na-
tional political representatives or functions (as these will
likely be motivated by similar mechanisms), or between
different public agencies guided by similar statutes and
missions, or between different individual pharmaceutical
companies of the same type, and so on. We do, however,
identify different types of political, public, business or
non-governmental bodies that seem to act out of rele-
vantly different types of interests as well as institutions
that perform clearly different roles and are thus able to
exert influence in different ways.
The outcome of this analysis is a network of actors
with attached interests and options to act that may
affect the options and/or stakes of at least one other
actor. This result is an important step to come closer to
a comprehensive prescriptive social network analysis
[22,23]. Moreover, this step already facilitates informed
hypotheses of promising policy directions, and analysis
of the proper sharing of responsibility to have such
policy development initiated. The entire network is
mapped and described in more detail in an Additional
file 1to this article. We use examples of specific
national actors to serve as illustrations of different
national actor types. These have been taken from
primarily two contexts well known to us, India and
Sweden.
In our conclusions, we also present a qualified general-
isation of the results related to these specific examples,
noting methodological limitation with regard to details:
while in many cases institutions in different countries
may perform similar roles, one cannot simply presume
that our analysis applies throughout different social and
legal contexts. Differences in institutional structure need
to be taken into account as this can determine what
measures are most effective. In what follows, it will be-
come clear that the properties of producer countries
tend to be more easily generalisable than those of the
consumer countries, due to the complex institutional
structures that are relevant to licensing, sale of drugs,
health insurance, hospital care and so on. This limitation
therefore mainly affects consumer countries. However,
as we will argue, there are nonetheless valuable lessons
that apply to all consumer countries and what remains
will be important topics to address in future research.
From here on, the presentation refers to the separate
Additional file 1linked to this article, and we will
henceforth refer to the actor types detailed in this
Additional file 1by inserting # and the number given
to them there in parenthesis.
Results
The Additional file 1details 33 separate actor types of
potential importance, summarised in Table 1.
When analysing how the actor types and their interests
link to (possible) incentives and disincentives, we have
proceeded from the most immediate source of pollution
the pharmaceutical industrial plant emitting pharma-
ceutical residue, in particular subcontracted producers
of API. Below, we note some of the most important (dis)
incentives for this category of actors and the relation
between various producers (branded, generic, subcon-
tracted) of antibiotics, as well as public actors in produ-
cer countries. We then focus on a crucial element of any
viable solution, namely increased transparency in the
supply chain. This for the simple reason that transpar-
ency is a crucial element for other actors to be able to
act on pollution, since that requires information on who
creates the pollution, to what extent, and what the sup-
ply chain looks like. After this, we examine the role of
actors in consumer country states (Sweden), such as
regulators and governmental institutions, but also
pharmacies, media and hospitals.
Before considering possible options in some area in
need of action, it is important to consider what actors
are able to implement the suggested actions. How
different actors are related to the area of industrial
antibiotics is not always straightforward. The most
obviously involved type of actor is the pharmaceutical
industry (#1-#5 & #7). However, as we show in the
Additional file 1, once the active pharmaceutical in-
gredients (or APIs) are produced by subcontracted
companies (#3), these are often distributed across the
globe by business networks (#1-#3, #7) which are
complex and often opaque, at least for the final cus-
tomers and users (#20, #23, #24, #26, #28). Through
the mechanisms of global trade and linked regulation
(#12) [20], the final antibiotic products eventually find
their way to what we label consumer countries(see
Additional file 1for more detail). Depending on local
regulative systems (#14-#19, #21, #22, #30, #31) and
Nijsingh et al. Environmental Health (2019) 18:95 Page 3 of 17
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Table 1 Thirty-three actor types with possibilities to contribute to the reduction of antibiotic emissions from manufacturing. For
each actor type, examples of their interests, possible actions and incentives and disincentives for those actions are listed (more
details to be found in the main text and the supplementary material). Broadly common interests among actors, e.g. individuals/
employees desire to contribute to positive societal change (reducing pollution, improving public health) are implicit but have not
been listed for each actor. For actors #15, 16, 17, 21 and 22 we have listed Swedish examples of actors types
Actors Interests Actions Incentives Disincentives
# 1 Research-based
pharmaceutical companies
- Increase turnover, reduce
costs;
- Strategic interests
(e.g. stay ahead of the
curve);
- Reputation concerns;
- Preserve effectiveness of
product by curbing
antibiotic resistance.
- Motivate #3: demand good
pollution control for the
APIs they buy;
- Monitor & reduce their own
discharges;
- Set internal discharge limits;
- Act transparently with
regards to production sites
(also of suppliers) and
environmental performance.
- Emission standards;
- Legal requirements;
- Economic incentives (price,
costs, turnover);
- Pressure from investors and
buyers;
- Reputation concerns.
- Transparency as a threat for
reputation concerns;
- Higher production cost;
- Lack of follow-up of external
demands - risks of unfair
competition.
#2 Generic pharmaceutical
companies
- Increase turnover, reduce
costs;
- Strategic interests
(e.g. stay ahead of the
curve);
- Preserve effectiveness of
product by curbing
antibiotic resistance.
- Motivate #3: demand good
pollution control for the
APIs they buy;
- Monitor & reduce their own
discharges;
- Set internal discharge limits;
- Act transparently with
regards to production sites
(also of suppliers) and
environmental performance.
- Emission standards;
- Legal requirements;
- Economic incentives (price,
costs, turnover);
- Pressure from investors and
buyers.
- Higher production cost;
- Lack of follow-up of external
demands - risks of unfair
competition;
# 3 Subcontracting
pharmaceutical companies
- Increase turnover, reduce
costs;
- Strategic interests
(e.g. stay ahead of the
curve);
- Preserve effectiveness of
product by curbing
antibiotic resistance.
- Monitor and reduce their
own discharges;
- Set internal discharge limits;
- Act transparently with
regards to environmental
performance.
- Emission standards;
- Legal requirements;
- Economic incentives (price,
costs, turnover);
- Pressure from investors and
buyers (i.e. #1 & #2).
- Higher production cost;
- Lack of follow-up of external
demands - risks of unfair
competition;
# 4 Umbrella organisations/
collaborations between
pharmaceutical companies
- Represent members
(#1, #2, #3);
- Align interests of members.
- Coordinate action - In addition to those
applying to #1,2 and 3:
become a stronger force for
promoting common
interests.
- Interest and priorities may
differ between members.
#5 Owners of pharmaceutical
companies
- Profit on investment;
- Reputation concerns.
- (Threaten to) withdraw
investments in #1, #2 and
#3;
- Power through
representation in boards.
- Pressure from customers
and interest groups;
- Financial incentives (risk for
loss of business associated
with scandals).
- Limits on (short-term)
profits, as owners set profit
expectations.
# 6 Waste water treatment
plants (WWTPs)
- Increase turnover, reduce
costs.
- Implement more effective
treatment;
- Monitor and report
emissions.
- Government legislation;
- Subsidies.
- Costs.
# 7 Parallel importers - Increase turnover, reduce
costs.
- Promote transparency and
regulations.
- Pressure from buyers;
- Legislation.
- Very limited ability to gain
information on, or to
influence the production
chain.
# 8 Producing country states - Represent population;
- Protect public health;
- Protect economic interests.
- Regulate industry in terms
of emissions;
- Pressure, negotiate with #1
3;
- Sponsor research and
knowledge transfer;
- Support infrastructure.
- Political pressure from
citizens and interest groups;
- Treaties, multilateral
agreements, foreign
pressure;
- Public health concerns.
- Economic interests:
protecting current industry -
strict standards may create
disadvantages for national
producers;
- Lobbying by #13.
# 9 Environmental oversight
agencies
- Follow statutes and
directives as defined by #8;
- Protect the environment
(and public health)
- Implement and enforce
rules and regulations;
- Provide data on emissions.
- Pressure from various actors;
- Directives deriving from #8.
- Pressure from #13, in
particular on the local level.
# 10 Citizens of producer
states
- Economic concerns;
- Public health;-
environmental protection.
- Pressure industry and
government;
- Vote.
- Awareness;
- Economic, health and
environmental interests.
- Lack of information/
awareness;
- Lack of interest;
- Lack of effective political
power.
Nijsingh et al. Environmental Health (2019) 18:95 Page 4 of 17
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Table 1 Thirty-three actor types with possibilities to contribute to the reduction of antibiotic emissions from manufacturing. For
each actor type, examples of their interests, possible actions and incentives and disincentives for those actions are listed (more
details to be found in the main text and the supplementary material). Broadly common interests among actors, e.g. individuals/
employees desire to contribute to positive societal change (reducing pollution, improving public health) are implicit but have not
been listed for each actor. For actors #15, 16, 17, 21 and 22 we have listed Swedish examples of actors types (Continued)
Actors Interests Actions Incentives Disincentives
# 11 Citizen interest groups,
environmental and human
rights NGOs
- Represent #10;
- Represent particular
interests.
- Coordinate action;
- Create awareness;
- Exert pressure.
- Pressure from supporters;
-Mediagenicaction may be
more attractive with an eye
on public support.
- Limited political power.
# 12 Inter-governmental polit-
ical forums (eg. G7)
- Coordinate and represent
national and international
interests.
- Apply political pressure;
- Harmonize policies.
- Input by goverments,
political leaders;
- Pressure by interest groups,
political organisations etc.
- Many different interests,
they may not always align.
# 13 United Nations agencies - Initiate and harmonize
collective action on global
problems.
- Create awareness;
- Harmonize policies across
nations;
- Exert pressure on industry
and governments.
- Pressure from governments,
interest groups, political
organisations etc.
- Limited power.
#14 Consumer country states - Represent population;
- Protect public health;
- Protect economic interests.
- Regulate;
- Establish premiums;
- Direct research funding;
- Direct actions by national
agencies;
- Influence other consumer
states and # 30.
- Political pressure by citizens
and interest groups;
- Treaties, multilateral
agreements, foreign
pressure;
- (Global) public health
concerns.
- Economic interests: costs
- Lobbying by #13;
- Little mass, individually
(higher cost to establishing
premiums);
- Institutional barriers (eg.
state generic substitution
system).
# 15 National Licensing
agencies (Läkemedelsverket,
LV)
- Follow statutes and
directives as defined by #14;
- Good, affordable health
care.
- Implement standards and
licensing of medical
products;
- Steering by national
government.
- Limited mandate.
# 16 Agencies committed to
subsidizing decisions (Tand-
och läkemedelsfömånsverket,
TLV)
- Follow statutes and
directives as defined by #14;
- Good, affordable health
care.
- Effective resource allocation.
Potentially (but not currently):
- Weigh environmental
concerns in reimbursement
decisions.
- Steering by national
government.
- Limited mandate;
- Limited possibilities for
action under current
statutes.
# 17 Agencies committed to
prescription policies
(Socialstyrelsen, SoS, and
Inspektionen för vård och
omsorg, IVO
- Follow statutes and
directives as defined by #14;
- Good, affordable health
care.
- Issue national treatment
guidelines (in cooperation
with # 18).
- Steering by national
government.
- Limited mandate.
#18 Public health agencies - Follow statutes and
directives as defined by #14;
- Good, affordable health
care.
- Issue national treatment
guidelines (in cooperation
with # 17)
- Steering by national
government.
- Limited mandate.
#19 Agencies committed to
public procurement:
Upphandlingsmyndigheten
- Follow statutes and
directives as defined by #14;
- Good, affordable health
care.
- Supporting #20, 21 and 22
to put pressure on # 1 and
2
- Steering by national
government.
- Limited power.
#20 Public hospitals and
clinics
- Follow statutes and
directives as defined by #14
and #21;
- Represent interests of #26 &
#28;
- Effective resource allocation.
- Apply environmental criteria
in procurement;
- Improve awareness.
- Regulation. - Pressure on cost-efficiency;
- Limited negotiating power.
#21 Regional government
(county council) and their
regional medical products
committees (Läkemedels-
kommittér)
- Represent population;
- Protect public health;
- Good, affordable health
care;
- Protect economic interests.
- Steer #20;
- Weigh in environmental
concerns in regional
treatment
recommendations.
- Political pressure by citizens
and interest groups;
- National policies;
- Public health concerns.
- Limited power.
#22 Central priority setting
organisation for drug
procurement (NT-rådet &
Sveriges kommuner och
landsting, SKL)
- Effective resource allocation;
- Good, affordable health
care.
- Help counties act jointly
and effectively.
- Steering by national
government.
- Limited mandate.
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Table 1 Thirty-three actor types with possibilities to contribute to the reduction of antibiotic emissions from manufacturing. For
each actor type, examples of their interests, possible actions and incentives and disincentives for those actions are listed (more
details to be found in the main text and the supplementary material). Broadly common interests among actors, e.g. individuals/
employees desire to contribute to positive societal change (reducing pollution, improving public health) are implicit but have not
been listed for each actor. For actors #15, 16, 17, 21 and 22 we have listed Swedish examples of actors types (Continued)
Actors Interests Actions Incentives Disincentives
#23 Privately funded and
operated clinics and hospitals
- Profit;
- Promote and protect health
of their patients.
- Apply environmental criteria
when buying antibiotics.
- Demands made by
subcontracting county
councils;
- Pressure from #28, 29.
- Very little negotiating
power.
#24 Pharmacies - Profit;
- Reputation concerns.
- Take environmental
concerns into account
when purchasing antibiotics
(applicable to some
countries, not all);
- Improve awareness.
- Media attention;
- Attracting costumers.
- Little or no influence over
what antibiotics to provide
through governmental
restrictions (in some
countries, but not all).
#25 Insurance companies - Profit;
- Reputation concerns.
- Negotiate, pressure # 1,2. - Financial considerations (e.
g. premiums, or taxes).
- Interest in lower prices.
#26 Physicians and other
health care professionals
- Economic interests (in some
settings);
- Professional ethos.
- Pressure, primarily through
#27.
- Increased awareness.
- Pressure from lobby groups,
particularly #1,2 and 4 (in
some settings)
Lack of information/
awareness
- Lack of interest/time;
- Lack of effective political
power.
#27 Physician and other
health care professional
organisations
Represent interests of #26. - Pressure relevant policy
makers and institutions.
- Create awareness among
members, the public,
politicians and policy
makers.
- Pressure by members. - Lack of effective political
power.
#28 Patients/citizens of
consumer country states
- Keep costs for medicines
low;
- Access to antibiotics.
- Support NGOs;
- Vote, exert political pressure;
- (When possible) buying
environmentally certified
antibiotics.
- Awareness. - Lack of information/
awareness;
- Lack of interest;
- Increased costs for
medicines;
- Lack of effective political
power.
#29 Patient organisations Represent interests of #28. - Pressure on county
governments or inter-
regional coordinating
bodies;
- Improve awareness.
- Pressure by members; - Lack of effective political
power.
#30 Multinational governing
bodies (e.g. the EU)
- Represent member states;
- Streamlining the national
policies.
- Regulate;
- Negotiate, pressure;
- Subsidize sustainable
practices;
- Research funding.
- Political pressure;
- Treaties, multilateral
agreements, foreign
pressure.
- Non-aligning interests be-
tween member states;
- Lobbying;
- Lack of jurisdiction. Outside
of e.g. EU.
#31 Agencies of multistate
bodies (such as the European
Medicines Agency)
- Follow statutes and
directives as defined by #14.
- Amend licensing
requirements (ERA) to
include risks for AMR
selection and production
emissions;
- Include environmental
considerations in GMP;
- facilitate transparency of
production chains.
- Steering by #30. - Lack of research data to
define demands;
- Lack of jurisdiction outside
of e.g. EU.
#32 Media - Profit;
- Credibility;
- Public interest.
- Improve awareness;
- Expose polluters;
- Demand action from the
majority of actors.
- More viewers/readers;
- Curiosity;
- Increased credibility.
- Opacity of productions
chains;
- Lack of emission data.
# 33 Scientific researchers
and universities
- Reputation;
- Receive funding.
- Generate knowledge;
- Educate and create
awareness among other
actors;
- Propose scientifically funded
actions for e.g. regulation
and procurement.
- Curiosity With
- Reputation;
- Funding;
- Institutional barriers to
multidisciplinary and/or
international cooperation;
- Limited access to data and
samples from industry.
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market dynamics, different demands and prices are
set in different places, and a combination of the com-
mercial actors interact with each other, as well as fur-
ther ones, in chains of distribution, retail and
procurement. Although producer countries are also to
some extent consumer countries, and many consumer
countries are also to some extent producer countries
(by hosting producers and distributors), we suggest
that this distinction helps to understand the various
interests in play.
India and China are the largest hosts of subcontracted
producer of APIs (#3), at least for generic medicines.
Europe and the USA on the other hand, host the largest
research-based companies (#1), while also representing
large and economically strong markets for the consump-
tion of antibiotics. However, even though the majority of
the final medicinal products available on, for instance,
the Swedish market are produced in Europe, the APIs
used by these European producers originate to a much
larger extent from other parts of the world, often
countries that have been ranked as those with in general
poor environmental standards´ [20,24]. To simplify,
consumer states often outsource[10] the pharmaceut-
ical pollution generated by their high consumption
levels. For this reason, there will be differences between
the typical interests of consumer states (#14), compared
to producer states (#8), as the former have more indirect
stakes in reducing emissions, while they have a direct
interest in reducing health care costs.
Any of the types of actors described in the Additional
file 1can conceivably affect the extent of pollution by
some type of action. At the same time, the actual choice
regarding such actions will be guided by a wide variety
of interests, and take place in a very complex landscape
of other actors and interests. In what follows, we go on
to examine in what way the actors may contribute to a
solution and how the levels interact, analysing what
incentives and disincentives may be created for producer
actors, and for key actors in consumer countries, using
Sweden and India as examples.
The role of subcontractors in producing countries
Currently, there are limited legal or economic incentives
for subcontracted producers (#3) to act in order to im-
prove the situation regarding industrial antibiotics pollu-
tion. Recent initiatives by the pharmaceutical industry to
address pollution indicate that the need to change is
recognised primarily among some research-based com-
panies (#1) [13,25] but the economic costs involved
disincentivize all producers from voluntary change as
evidenced by the fact that cases of substantial pollution
are revealed regularly [10,26]. Obvious costs of environ-
mentally improved antibiotics production relate to more
extensive efforts to avoid contamination of wastewater
in the first place or to install effective treatment (#6).
This may lead to a smaller market share, if the costs are
reflected in increased prices, or otherwise result in a di-
minished profit margin. If the market shares remain the
same while profit margin goes down due to increased
production costs, this means that the value of the mar-
ket is diminished, which in turn affects the future flow
of new investor capital. Likewise, information on the
level of pollution at individual production plants and
how to assess these in a scientifically supported and reli-
able way is currently severely lacking [6,1012,17,27,
28]. For this reason, setting up reliable systems to moni-
tor emission levels and types, and assessing when levels
are acceptable and when they are not, would be a major
research and development investment, involving sub-
stantial scientific, technical and staffing costs. The more
that these costs have to be carried by individual produc-
tion companies (#1-#3), the more they will constitute a
serious disincentive of both these companies and their
owners (#5), as well as states and individuals that benefit
from their business (#8, #10), to go along with requests
for better control of industrial antibiotics pollution.
One way to provide incentives for desirable change of
subcontracted producers (#3) is, then, for other actors
within the manufacturing country to take on (some of)
the costs and the logistical arrangements needed for an
effective management of industrial antibiotics pollution.
For instance, the national government as well as regional
governments (#8) may sponsor research and develop-
ment, financially support technological arrangements,
subsidize the cost of waste water treatment plants (#6)
to assist in improved wastewater management, and so
on. In addition, governments may offer softer incentives
by initiating collaborative talks with industry and create
benefit schemes for better performing companies. For
example, the Chinese government stimulates their
pharmaceutical sector and offers a competitive advan-
tage by providing cheap electricity, land, water, and
waste disposal to companies that perform well in various
respects, including transparency measures and environ-
mental control [29]. Finally, the government can, of
course, add incentives through regulatory arrangements,
laws, taxes, as well as charters for public agencies over-
seeing pharmacological industry, environmental safety,
etcetera. Here, the national environmental agencies, such
as the Central Pollution Control Board (CPCB) to take a
specific Indian example (#9) may conceivably play a
larger role in surveillance and enforcement of standards.
However, to what extent the rather ambitious plans by
Indian government to curb pollution will be successful is
yet to be demonstrated [15,30]. Note that all of these
ideas shift the question to what incentives there are for
these governmental actors to actually take up this role of
incentivizing producers. The financial, logistical and
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infrastructural costs have to be paid somehow, at the
end of the day by taxpayers who are also donors and
voters (#10). For a politician regional or national
this provides a disincentive to taking the action that
would incentivize all of the other actors to pressure and
assist the API producer.
Other actors that are in a position to incentivize sub-
contracted producers (#3) very directly would be their
customers (contractors), i.e. research-based (#1) and
generic drug producers (#2). If these actors start to re-
quire of their subcontracted producers to certify a good
antibiotics pollution management, it would provide an
immediate financial incentive for the latter to do so.
That would also create an incentive for the state hosting
the production (#8) to provide resources and institu-
tional frameworks to support such a development. How-
ever, this raises the question how to incentivize
research-based and generic producers themselves to
exert such pressure.
One incentive for this chain of actors would be if there
was an increase of internal national grass root political
pressure, and here the (national and international)
media, science and international organizations (#11, #13,
#27, #29, #31- #33) may help to move things forward by
creating awareness of the potential risks associated with
industrial antibiotics pollution. However, such change
usually moves slowly, and the question then arises what
can be done to incentivize action in the meantime. In
addition, while awareness may certainly move political
opinion, it is far from certain that it would suffice to
balance the mentioned disincentives, in particular the
financial, logistical and infrastructural costs.
Transparency in the supply chain
One important disincentive for action is the current gen-
eral opacity of the production and supply chain for
example simple information on what company produces
the API in a given product and where that production
takes place is considered confidential and is usually only
available to the authorizing agencies to facilitate quality
control. This makes it a complicated task for govern-
ments and institutions (#8, #14- #19, #30, #31) to create
effective systems for pollution control, or for third par-
ties (including consumers #28 and media #32) to exert
pressure by linking sometimes apparently polluting pro-
duction sites abroad to the companies selling the final
products in consumer states [18,20]. Pharmaceutical
companies may, of course, be motivated by reputation
concerns to avoid being perceived as antibiotics pol-
luters. Rankings of public perception [31] may have a
significant impact on certain companiesbehaviour, but
primarily those that consider branding a critical issue of
their business (#1). Again, this indicates that there is an
important role for scientists and media in revealing cases
of substantial pollution. Environmental agencies and
NGOs, both local and global, may play a similar role in
appealing to companies´ reputation concerns. NGOs
may not only apply political pressure, but can also
contribute by gathering data and documenting pollution
and its effects. By way exerting political pressure, such
strategies can enable for example patients, hospitals,
pharmacies and prescribing physicians (#20, #23, #24,
#26, #28) to exercise their power to apply pressure we
will further expand on how they may do this below.
Reputation concerns are particularly important for
research-based companies (#1), as these have a brand to
protect in the eyes of public perception. In contrast, gen-
eric producers (#2) and subcontracted producers (#3) do
not, or at least not to the same extent, have a need to
protect reputation in order to stay in business, as their
business model largely builds on providing quality prod-
ucts to a low cost. Reputation may also indirectly con-
cern many large investors in pharmaceutical companies
(#5), regardless of whether the companies are research-
based or generic producers. Financial institutions, such
as banks, insurance companies and pension funds, have
been shown to be sensitive to pressure from consumers
and advocacy groups (albeit slowly and not always ef-
fectively, see [32,33]). However, since protecting the
reputation of a market brand is connected to whether a
company seems to act in a responsible and sustainable
manner, not just whether they actually are, there is a
lack of incentive to push for a more transparent system.
Companies can be reluctant to share information to
make the production chain more transparent for the
very reason of protecting their reputation. These disin-
centives will also likely affect investors. Paradoxically,
therefore, reputation concerns may provide disincen-
tives to effective antibiotics pollution action. While
pharmaceutical companies show an increased willing-
ness to take antibiotics pollution seriously, [13]given
the current lack of transparency of how industrial anti-
biotic emissions link to specific producers, very few are
willing to disclose information that would make the
situation less opaque, such as identifying who their sub-
contractors are and what levels of antibiotics they emit
to the environment [14]. Authorising agencies, such as
the LV (#15) and the EMA (#31) do dispose over this
type of information, in order to ensure inspections
aimed at quality control, but they are not allowed to
publicly disclose this information [18,20].
However, had the production and supply chains been
reasonably transparent, the incentive coming out of a
research-based companys concern for reputation would
seem to have pulled in the opposite direction. Once a
company is tainted by a polluting production chain, it
starts to make good sense for research-based producers
(#1) and their owners (#5) to avoid being associated with
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such chains and promote those with a higher level of
sustainability. The higher the awareness and concern
about industrial antibiotics pollution is, the stronger the
rationale is not to be associated with it. This is for ex-
ample the case in Sweden, and increasingly so in other
high-income countries. Based on this, research-based
companies acquire reasons to pressure subcontracted
producers (#3), and thereby initiate a chain of incentives
for constructive change supported by producer countries
(#8) in line with what was envisioned above. However,
generic producers (#2), as observed, will not be incentiv-
ized to the same extent (as their brand is not as critical
to protect), which means that insofar as the sales for
generics are not that sensitive to improvement in trans-
parency, these producers will be less incentivized to
pressure subcontracted producers. Unfortunately, this
factor will then add to the disincentives of research-
based companies to work for increased transparency of
the production chain, since this would put them at a
relative business disadvantage when compared to the
generic producers. While generic producers would be
able to buy APIs more cheaply from subcontractors,
research-based companies would have to carry parts of
the costs for a more sustainable API production.
It should be clear at this point that understanding how
markets function is important for the analysis of how to
incentivize producers, and relevant actors in producer
countries, towards more sustainable practices with re-
gard to industrial antibiotic pollution. In a market, the
relative advantages and disadvantages of stakeholders
are in the forefront of how business actors (and those
with interests closely linked to these) assess the attract-
iveness of a more environmentally sustainable strategy.
Unless there is an added benefit, companies are under-
standably reluctant to exert themselves overly when the
competition is unlikely to incur similar costs. This stra-
tegic consideration illustrates the importance of finding
ways to incentivize all types of producers (#1-#3)
equally, in turn pointing to the importance of creating
internationally harmonized policies and to an important
role for internationally coordinating institutional actors
(#12, #13, #30, #31). On the other hand, there is a
danger in strategies that rely on all relevant actors being
on board: aiming for global or multinational consensus
across many or all actor types may well lead to a
situation where actors passively await action by others.
The role of actors in consumer countries (Sweden)
Given the multinational and complex nature of both
the drug market and international politics and trade,
the relevant actors involved are not confined to those
within the borders of the countries where the pro-
duction and therefore the pollution takes place. As
outlined in the Additional file 1, the production of
APIs cannot be seen in separation of the international
supply chains and the background of the international
regulative landscape. This observation moves our
search light from the producers and producer countries
to those that dominate consumption.
Although, as we will show, there is good reason to
look at consumer countries in developing a response to
industrial antibiotic pollution, there are significant ob-
stacles in the way. A disincentive that stands out is an
unwillingness to accept increased healthcare costs, as
all of the incentives for industry mentioned can be ex-
pected to be reflected in pharmaceutical prices. Systems
for generic substitution of drugs that we will discuss
below are a particularly institutionalized example of
this disincentive. However, there are various ways to
counter such obstacles. Below, we highlight licensing,
reimbursement and procurement mechanisms. It
should be noted that media and scientific researchers
(#32, #33) play a role in increasing awareness among
institutional and political actors in high-income con-
sumer states such as Sweden (#14 - #25), and inter-
national political collaborative organisations, such as
the EU and the UN (#12, #13, #30, #31), help to pro-
mote this sort of development. We will start by map-
ping out potentially effective ways to create incentives
for actions that may bring about positive change, and
after this list disincentives to such actions actions.
One powerful tool to motivate pharmaceutical compan-
ies is through licensing requirements and the routines of
institutions in charge of implementing these (#15, #31). In
the EU, licensing of medicinal products is to a large extent
harmonized, which offers promising opportunities. When
applying for a European marketing license, pharmaceutical
companies are required to submit an environmental risk
assessment (ERA) to the EMA or a national competent
authority within an EU country [34]. The ERA covers a
broad set of environmental assessments with a clear possi-
bility to incorporate considerations relating to antibiotic
resistance. However, to date, such risks are not covered
within this regulation. Also, only pollution associated with
usage (not production) is covered within the ERA. The
need for amending the ERA to bridge these two gaps have
been pointed out earlier [17]. At the same time, in prac-
tice, there is no penalty for non-compliance and products
are not withheld from the European market based on
non-compliance with the ERA [17]. In contrast, the risk-
management plan, which assesses amongst other things
the safety of the medicine for the patient, is used to deter-
mine eligibility for a license on the European market, and
similar mechanisms may be used by national agencies.
Addition of an amended ERA to cover industrial pollution
as a required ingredient in the risk-management plan (and
equivalent national requirements), would therefore pro-
duce a substantial incentive for companies to mind about
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the sustainability of their production chain. In addition, it
would be a basis for licensing agencies to require transpar-
ency of this chain for the purpose of assessing the envir-
onmental footprint of a drug, specifically with regard to
antibiotic pollution. Of course, in order to accurately offer
such assessments, in turn, it would be important that such
a move is accompanied by research on the risks of indus-
trial pollution. We return to this point later. Such a re-
quirement may be applied to both research-based and
generic producers, and may be extended also to parallel
import distributors in regulations for permission to trade
in drugs, all in order to create equal conditions on the
market. At the same time, the nature and function of
the risk assessment involved in the licensing of drugs
means that considerations relating to pollution would
have to be weighed against other considerations, such
as need, efficacy, safety, and the availability of alterna-
tive treatment [17]. This means not only an uncertain
outcome, but also possible risks of ethical controversy
and political backlash [35].
More robust incentives of this kind could be created
through the fact that pharmaceutical companies active
on the European market are bound by the EMA Good
Manufacturing Practices [36]. These are not relative in
the way that single risk factors in the risk management
plan are. Although currently environmental consider-
ations are not considered in the GMP, they could be
devised to include discharge limits, requirements of
disclosure with regard to production chains, and other
relevant demands to secure a minimum level of sustain-
able production practices. As the possibilities to follow
up on requirements and effectively control compliance
are currently limited [10,17], such control would require
stronger international collaboration, something on which
the European Commission hints in the EU action plan
[37]. Unfortunately, however, the action plan remains
vague about the specifics of such support, and focuses
mostly on the value of more knowledge, without com-
mitting to robust incentives in the pharmaceutical mar-
ket, let alone licensing practices. To get the ball rolling
towards incentivizing research-based and generic pro-
ducers to become more transparent with regard to
production chains, and to require of subcontracted API-
producers to monitor and disclose emissions, as well as
to mitigate these emissions to acceptable levels, explicit
regulatory requirements seem to be necessary. This
probably requires national and international political ac-
tion by high-income consumer states (#12-#14, #30), but
once that ball is set in motion, incentives for institu-
tional actors to assist and press industry actors and
producer country institutions will likely follow. What
could be such a starting point are the discharge limits
for 111 antibiotics we proposed in late 2015 [26]. These
were immediately highlighted in the British AMR review
[38] and later adopted as voluntary target concentrations
by many leading antibiotic manufacturers [13] and they
have also become the basis for the proposed Indian
regulation [15].
As mentioned, licensing agencies have access to data
on the origin of APIs, but they are not allowed to pub-
licly disclose this. A complementary action is therefore
to require that information detailing the production sites
of antibiotic products are made publicly available, as this
would open up the environmental performance of the
production chains for public scrutiny. Such information
could be given on websites, (for example the producers
own or that of the European Medicines Agency (#31))
alternatively labelling on containers (which is highly reg-
ulated) or pharmacy shelves [39]."(see below)" The infor-
mation could include the exact location of where the
constituting APIs are produced and formulated (a men-
tion of only the country or region of origin would have
very limited value [20]), the companies involved in these
stages of the drug production, as well as information on
applied discharge limits (voluntary or enforced) and the
documented level emission control. However, this type
of strategy becomes effective only when it feeds into a
consistent customer demand mechanism that will create
incentives for companies to offer products produced
under demonstrably sustainable conditions. When the
distribution of drugs in general, and antibiotics in par-
ticular, is controlled directly or indirectly (for example
through prescription guidelines) by national or regional
institutional actors within consumer countries, this may
be the case to the extent that these actors make explicit
requirements with regard to production chain disclosure
and guaranteed emission levels. However in large parts
of the world, particularly in low- and middle-income
countries, the market in antibiotics is not consistently
institutionalized and there are no, or very weak, pre-
scription requirements, and most health care and phar-
macy is operated through small-scale private actors [40].
In these health systems, increased public awareness
created through actions by the media, NGOs, patient,
professional and academic actors (#27, #29, #32, #33)
may help to produce some effect. However, in both cases
the effects of such incentives are uncertain. Once again,
this moves the search light to consumer countries, and
the way their internal actors choose to position them-
selves. For those countries that lack institutional control
over drug distribution and consumption, the first step
would then be to create the needed frameworks, ad-
mittedly a formidable political task for these consumer
states. In the following, we limit ourselves to high-
income consumer countries that do have such frame-
works, taking our specific examples from Sweden.
The Swedish government (#14) has so far addressed
the issue of the environmental dimensions of
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pharmaceuticals with greater force than the EU (#30), al-
though there is some recent progress in the European
context as well [41]. For example, on instruction from
the government, the licensing authority Läkemedelsver-
ket, LV (#15), has explicitly addressed the issue of
pharmaceutical pollution [42]. However, the resulting in-
centives are still limited, due to similar factors as already
mentioned in the case of EMA. Although LV has made
constructive proposals to incorporate more stringent de-
mands in ERA and Good Manufacturing Practices as
formulated by the EMA, they have little, if any, room in
this respect to pursue a course independent from the
European context. A revised GMP framework would put
equal demands on all antibiotics sold on the European
market, but progress in this direction has been slow.
Additionally, a Swedish government white paper [43]
has suggested that an alternative way of creating incen-
tives for environmental adaptation lies within the frame-
work of the pharmaceutical reimbursement system,
covering part of the costs for prescription medicines
[43]. During the reoccurring process of assigning which
single product (out of often several clinically inter-
changeable products) that should be subsidised, the idea
is that an environmental premium should be given to
those products/manufacturers that meet certain criteria
(yet to be defined) relating to emission control, thereby
making it easier for them to be selected, despite that
they may not offer the least expensive product. It is clear
that such a system, if the premium is sufficiently high,
may do much to address the issue of stimulating greater
transparency and offer a strong concrete business incen-
tive for industry to curb emissions. An immediate ques-
tion that arises, however, is how such a system should
be designed, who would end up paying the cost, and
how motivated key political actors will be to accept
them. In addition, a well-functioning premium system
involves calculating the environmental costs, establishing
criteria for conformity etcetera [43].
The LV also makes decisions on the interchangeabil-
ity of drugs within the Swedish generic substitution
system[44]. The Swedish system dictates that if two
drugs are interchangeable, the cheaper of the two will
begivenpreferenceinthesubsidizing and healthcare
procurement system. The criteria for interchangeability
relate solely to clinical risks and benefits, meaning that
generic producers with lower production costs are
often favoured against research-based producers and
there is no special consideration of environmental
considerations. However, given these decisions on
interchangeability, the public subsidy authority Tand-
vårds- och läkemedelsförmånsverket (TLV, #16) may
act within its authority on the allocation of the public
subsidy of drugs. When comparing products which are
considered interchangeable, the TLV could theoretically
include pollution criteria, such as requirements related
to industrial pollution [43]. This would incentivize not
only research-based producers, but also generic
producers. Yet, given the current assignment by the
government instruction, there are no such pollution
criteria and TLV has no authority to place them. Thus,
TLV appears to have very little room to make substan-
tial environmental demands.Furthermore,intheEU
(and Sweden), this particular incentive will be limited,
as generic substitution only comes into play after a
patent has expired [43,45]. On the other hand, the
overwhelming amount of antibiotics (in terms of doses,
not necessarily money) are for antibiotics whose patents
are indeed expired [20].
Finally, either the Swedish government, or the EU col-
lectively, may attempt to exert influence by levying taxes
on products that do not fulfil certain environmental
criteria. Although it is beyond our expertise to comment
on the legal opportunities for such a solution, we acknow-
ledge the challenges involved in agreeing on criteria and
determining an effective, still acceptable, taxation level,
especially in an opaque context. These problems are fur-
ther exacerbated by the complicated task of reaching
agreement on taxes and the ways to implement them,
especially in an international context.
All of the governmental actors mentioned above may
thus act to include in their decision rationales consider-
ations related to industrial pharmaceutical pollution,
although not in all cases under the current statutes. This
may take the form of both an internalized external cost
that counts as a reason against buying or prioritizing a
drug, and of a benefit when companies demonstrably act
to make pollution management more sustainable. How-
ever, as documentation is lacking on the basis of which
the necessary assessments for such policies could be
made, more information regarding the actual level of
pollution management would be required [11,43].
The role of other stakeholders in consumer countries
In theory, pharmacies could also be an important actor
with regard to generic substitution, having patients
select the environmentally more preferable among thera-
peutically equivalent drugs. In Sweden, however, they
would be constrained by the generic substitution system,
and the decisions by LV and TLV for prescription drugs
(which all antibiotics are). Unless these latter actors
weigh environmental factors into their decisions, this
remains impossible for pharmacies. In states where
pharmacies have a license to act more autonomously,
this role may remain open. Another way in which phar-
macies may contribute to the right incentives, is by
labelling practices. For example, there is in Sweden a
voluntary labelling initiative by the private pharmacy
chain Apoteket Hjärtat, which involves labelling on the
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shelf. This labelling is, however, limited to procedural
company characteristics, whether they follow a certain
reporting system and are part of the pharmaceutical
supply chain initiative[39,46]. Also, and more import-
antly, such labelling practises by the pharmacies are not
applicable to prescription drugs.
Separate from the pharmacies (and thus the issue of
interchangeability), incentives may be offered in the con-
text of public procurement [47,48]. As described in the
Additional file 1, Swedish public hospitals and primary
care clinics (#20) are usually either owned or subcon-
tracted by the county councils (#21), who buy and nego-
tiate antibiotics. The amount is relatively minor when
compared to the total amount of the antibiotics that are
used in Sweden, but still substantial. In addition, county
councils subcontract to privately owned hospitals and
clinics. County councils are therefore in a unique pos-
ition to lay down environmental demands, and therefore
may contribute an important piece of the puzzle in pro-
viding effective incentives to pharmaceutical companies.
Nationally, the public procurement agency, Upphan-
dlingsmyndigheten (#19), in turn, can help guide county
councils in a supporting advisory role. In addition, the
inter-regional body for national price negotiation and
priority setting of new treatments within the
organization of counties and municipalities, especially
NT-rådet (#22) [49] can help counties act jointly and
effectively by taking environmental considerations into
account when assessing the overall value of a drug, and
make environmental demands in these negotiations.
Additionally, county government (#21), which has the
final mandate to decide what treatments are on the
menuto be procured by public hospitals and primary
care, may take similar steps with a similar impact.
Another possible pathway to create incentives based
on LV and EMA decisions on drug licenses is clinical
guidelines. We have already mentioned regional com-
mittees issuing recommendations on what drugs to use
for given indications (#21). At the same time the na-
tional agency, the Socialstyrelsen (SoS) (#17), has a
powerful and coordinating position role in issuing na-
tional treatment guidelines. Given the strategic threat to
the quality of healthcare generally, it may not be unrea-
sonable to have such guidelines allow room for environ-
mental health considerations as part of the rationale.
The government (#14) may give SoS such a charter, and
direct it to collaborate with the Public Health Agency of
Sweden (FHM) (#18) in this endeavour.
All ideas of changing the system for drug substitution
conflict with the underlying policy rationale of this sys-
tem. The point of such systems is to reduce the public
cost for pharmaceuticals by exploiting the competition
between research-based and generic producers. Generic
drugs ruled to be interchangeable are given fast access
to the market and public subsidy, thereby making
cheaper alternatives quickly procurable for healthcare.
Measures as the ones mentioned above mean that gen-
eric manufacturers (which are not as sensitive to other
pressures to control environmental emissions) will prob-
ably lose competitive advantage. At the same time, there
is a strong political interest in reducing healthcare costs,
linking to an interest across large segments of the public
in avoiding tax increases. This creates a disincentive
against implementing reform of the drug substitution
system that could incentivize producers to better control
industrial antibiotics pollution. This disincentive is an
unusually salient and specific example of how widely
embraced political aims to reduce pharmaceutical cost
in publicly funded health systems may undermine moti-
vation to take action that could incentivize industry and
producer countries to control industrial antibiotics pol-
lution. Simply, put, whatever actions are taken, these will
probably be reflected in drug pricing, and thus run con-
trary to currently prevailing economic health policy aims
on of many high-income consumer states.
In the long run, of course, this disincentive weighs
quite lightly compared to the primary value of having
an effective health system, which is in turn threatened
by antibiotic resistance. However, longer time horizons
are seldom very decisive in politics, unless there is a
stark public awareness of very serious threats. Here, as
before, media (#32), NGOs (#11) and academic and
professional actors (#26, #33) may act to shape a public
atmosphere weakening this disincentive. Especially aca-
demics and health care professionals are in a key po-
sition to provide the understanding and information in
order to prompt such a development, since, although
typically their audience is limited, scientists and health
care professionals play a crucial role in making the
relevant facts public.
A recurring disincentive for many of the actions that
could be taken by national institutional actors has its
root in well-known collective action problems related to
global problems [50,51]. There are Swedish county
councils (#21) that have requested from pharmaceutical
companies that emissions are monitored during manu-
facturing, but on their own their negotiating power vis-
à-vis multinational corporations is weak. Actors within
the counties, such as single hospitals (#20), the Läkeme-
delskommitté (#21), or pharmacies (#24) have even less
power in this respect. For this reason, nationally coord-
inating institutions like LV (#15), TLV (#16) and NT-
rådet (#22) are better able to act in this respect, but we
have also seen that their mandate is limited. Therefore,
the counties here primarily face an incentive to start act-
ing even more in coordination, in order to create an in-
centive for each to use the procurement and priority
setting incentive. However, even if the mandate would
Nijsingh et al. Environmental Health (2019) 18:95 Page 12 of 17
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
be expanded by the state (#14) to facilitate also more ef-
fective and well-coordinated national action, the state
level actors face a situation where the difference that
they can make on their own is limited. Sweden has a
relatively small mass in terms of drug industry revenue
(0.9% of the global market value of pharmaceuticals),
suggesting that any effective intervention of the types
mentioned is likely to be rather costly. If several coun-
tries together, the EU (#30), or better yet the global
community, were to formulate joint demands, this would
result in a much more powerful position to incentivize
large international industrial conglomerates. However, as
we have already seen, in the European context, let alone
the global one, the legal power of the relevant institu-
tions is relatively weak: the EMA (#31), for example, has
as its primary purpose streamlining the national policies
decided by single states, not initiating effective joint ac-
tion. This is a disincentive against EMA acting in the
direction sketched earlier to create incentives for
pharmacological companies to mind more about envir-
onmental factors. And as we move into global institu-
tions (#12, #13), while potential bargain power becomes
much stronger when these do succeed to act forcefully,
the political base to further an independent agenda to
restrict the policy options of sovereign states proportion-
ally weakens. Therefore, at the end of the day, this disin-
centive can be mitigated or removed only to the extent
that a sufficient number of single high-income consumer
states are motivated to coordinate effective action to
incentivize producer states and industry. Once again,
academic and professional actors, NGOs and the media
have a key role in incentivizing such motivation.
Another underlying disincentive to effective institutional
action (on any level) is the current lack of effective surveil-
lance systems and systematic emission data on industrial
antibiotic pollution [10]. This is the case because effective
action requires specific information to act upon, but also
because such information affects prioritization in order to
direct incentives to the appropriate targets. This holds on
the national (Swedish or other single consumer states) as
well as the multinational (EU and, ultimately, UN agen-
cies) level. Therefore, a first step needs to be to incentivize
better industry transparency with regard to production
chains, as well as demonstrable actions to monitor and
control emissions at the source [18,20]. Lack of transpar-
ency and documented action in this respect creates an
environmental health uncertainty that can be viewed as an
external cost for society that needs to be internalized in
different ways by different actors, thereby making a drug
less attractive for license, clinical recommendation, sub-
sidy, procurement and finally use. The higher this cost is
estimated by a societal institutional actor, the more force-
ful the incentive for companies to act in order to favour
their own products. Once a system of reasonable
transparency regarding production chains and quality as-
sured monitoring of emission levels is in place, the disin-
centive for societal actors is gone and the search light can
move to actual emissions, so that companies can be
rewarded for assuring effective curbing of antibiotics pol-
lution through measures at their own plants, or pressuring
on subcontracted partners.
Conclusions
In this paper we have mapped important incentives and
disincentives with regard to possible ways in which actors
that are directly or indirectly involved in the issue of in-
dustrial antibiotic pollution can be motivated to effective
action (incentives), as well as to obstacles that would hin-
der such action (disincentives). Taking account of all of
the actor types, and their possible incentives and disincen-
tives to act effectively in this area, as described in the
Results section, we may plot typical chains of actions and
resulting incentives (including overcoming noted disin-
centives), and use this as a starting point for actors to
decide how to design policies and specific measures and
where, more exactly, to direct these. Some examples of
such incentive chains, starting with public actors in con-
sumer countries, and ending up with better pollution
management by API producers, are illustrated in Fig. 1.
The collective action challenge presented by industrial
antibiotic pollution is an outcome of how effective
incentives to combat industrial antibiotics emissions rely
on action on different levels and how these levels
interact in sometimes rather complex ways.
We have presented a first step to a social network ana-
lysis in order to map these various actors and their inter-
actions. This interconnectedness, and the complexity it
involves, is itself a feature of the problem, and needs to
be taken into account when considering solutions. We
have shown how incentives for actions to curb industrial
antibiotics pollution are unlikely to arise without consid-
erable support action by consumer countries and the
international community. We have also demonstrated
that the creation of systems to make production chains
transparent, and emission levels controllable, plays a
crucial role in addressing the problem of antibiotics pol-
lution. Without such systems, very little actions of any
other kind seem likely to bring about positive change, no
matter what actor perspective we take.
The combination of these three challenges (complex-
ity, international dependency and need for better trans-
parency) are common to various ethical problems of a
systemic and global nature: think of diverse global
topics, such as climate change, human rights issues in
the production of globally traded consumer goods, ani-
mal welfare in meat production and the use of pesticides
in agriculture. For each of these areas, a relatively large
number of different actors constitutes a complex chain
Nijsingh et al. Environmental Health (2019) 18:95 Page 13 of 17
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
or network in which each of them is dependent on what
the others do.
As noted, some possible actions may create tensions
between different normative considerations. For in-
stance, incentivizing through reform of drug licensing
and clinical guidelines may create provocative tensions
between long-term environmental health considerations
related to industrial antibiotics pollution and ordinary
short-term clinical ethical considerations regarding
benefit and safety for patients in care. As mentioned,
political normative conflicts between short-term aims to
reduce healthcare cost may also conflict with many in-
centives that can be created by consumer state actors.
We do not argue for any particular resolution to such
dilemmas, neither have we come to any specific conclu-
sion on what from a normative perspective is the right
course of action for the various actors involved, although
we have pointed out some normative considerations.
This brings us to the delicate question of responsibility.
A knee-jerk response to the problem of pollution may
be to simply blame the ones who pollute. While we by
no means want to absolve those who discharge anti-
biotics, we think it should be clear however that in an
issue as diffuse as this, there is no single individual actor
that can be blamed as the sole culprit. And even if we
could this would still not free us of the obligation to
think about possible solutions, given the fact that some
actors fail to do as they should. Our suggestion here is
that, when thinking about solutions in that light, there is
a special role for governments of consumer countries.
We have three reasons for this.
First, producer country states will not be able to
solvetheissueontheirown.Althoughtheopportun-
ities to effectively and rapidly change legislation with
regards to emission are larger from within each pro-
ducer country, environmental regulatory measures
alone will likely not suffice. This means that we
should also look at economic incentives and aid for
capacity building in producer countries. Those actors
that have more financial resources to dispose over,
will be more likely to be able to change the dynamic
described in this paper. The mechanism here is
Fig. 1 Examples of chains of actions of different actor types to incentivize action of other actors to improve the management of environmental
industrial antibiotics pollution
Nijsingh et al. Environmental Health (2019) 18:95 Page 14 of 17
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
simple: the buyers of products have influence to the extent
that they represent more economic mass; the big buyers
of pharmaceutical products (the EU and the USA) thus
represent more economic power, especially if they
coordinate their actions.
Second, we have shown that there is a central role for
information when we look for possible solutions to cre-
ate better transparency. Once the information is avail-
able, effectively aligned systems in consumer countries
may stimulate sustainable production models. Transpar-
ency and controllability are thus crucial to the success of
any attempt to address systemic and global issues, and
this for two reasons. On the one hand, transparency and
controllability provide quality assured insight into the
problem and how possible solutions may proceed. On
the other, the notion of international cooperation re-
quires that actors have knowledge of what the others are
doing and how joint action pays off. This is not neces-
sarily an indication of mistrust, but a condition for creat-
ing meaningful options for action that can be viewed as
legitimate from the different perspectives of different types
of actors and different states. In order to address complex
issues such as industrial antibiotic pollution, we need to
consider in what ways actors can create space for other
actors to acquire information that is important for them
to act effectively downstream. Viewed in this way, pursu-
ing the construction of systems and standards for trans-
parency and control will likely mean very different things
on different levels. However, we have seen that there are
good opportunities from the legislative perspective of
consumer countries to affect the transparency in the pro-
duction and supply chain. Specifically, we have seen that
licensing, adapted reimbursement systems and procure-
ment may offer ways to enhance transparency.
Third, there is a need for increased knowledge on
for example the extent of emissions, the effects of
pollution on the emergence of resistance in patho-
gens, as well as the effectiveness of various economic
pressure mechanisms. Hence, a multidisciplinary ap-
proach is needed to bring science all the way to pol-
icy. We need to stress that there is sufficient
consensus on the risks involved already to initiate
measures, but better knowledge is likely to facilitate
more effective actions. Research initiatives should be
largely funded from within high-income consumer
states, for the pragmatic reason that they have more
financial resources. Yet collaboration on a global scale
is vital to success. Communication of existing know-
ledge, creating awareness among stakeholders, is also
key.
These three observations point strongly to the conclu-
sion that the greatest opportunity to create incentives
are mostly located in consumer countries, preferably in
collaborative concert. Given the complexity of the
network, the room to manoeuvre can be quite limited
for many actors. Less so, however, for some of the actors
in consumer states, and in particular not for those on
the level of consumer state governance. We argue that
here is a strong duty for actors who can do something
about the problem to actually take action. Exactly how
the most effective mix of regulation, aid and carrots
and sticksshould be designed will likely vary depending
on the economic, societal, legal and cultural context.
The analysis presented in this paper suggests several ex-
plicit actions where a chain of incentives and disincen-
tives may be influenced in order to effect change.
Supplementary information
Supplementary information accompanies this paper at https://doi.org/10.
1186/s12940-019-0531-1.
Additional file 1. Relevant actor types and their interests.
Acknowledgements
NN would like to thank Henrik Friberg-Fernros for the opportunity to present
a draft version of this paper at the Practical Philosophy and Political theory
workshop, at the Department of Political Science, University of Gothenburg,
on January 15 2019, as well as for his valuable comments on an earlier draft
of this paper.
Authorscontributions
DGJL conceived the idea, and developed the general approach of this paper
together with CM. NN analyzed the sources and drafted the first version after
that all authors contributed equally. All authors read and approved the final
manuscript.
Funding
This research was supported by the Swedish Research Council (VR) grant no
201805771 and the UGOT Challenges Initiative at the University of
Gothenburg.
Availability of data and materials
Data sharing is not applicable to this article as no datasets were generated
or analysed during the current study.
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests
Author details
1
Centre for Antibiotic Resistance Research (CARe), at University of
Gothenburg, Gothenburg, Sweden.
2
Department of Philosophy, Linguistics
and Theory of Science, University of Gothenburg, Gothenburg, Sweden.
3
Institute of Ethics, History and Theory of Medicine, Ludwig Maximilian
University, Munich, Germany.
4
Department of Infectious Diseases, Institute of
Biomedicine, The Sahlgrenska Academy, University of Gothenburg,
Gothenburg, Sweden.
Received: 27 April 2019 Accepted: 7 October 2019
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Supplementary resource (1)

... These concerns emphasize the necessity of regulating and reducing environmental pollution caused by pharmaceuticals, addressing the potential hazards that it poses to human, animal and environmental health. Various approaches can be employed to achieve this goal, involving different actors and stakeholders (Nijsingh et al. 2019;Malmqvist et al. 2023). Malmqvist and Munthe (2020) have identified four areas where new regulations can be introduced to encourage the pharmaceutical industry to adopt more sustainable practices in drug production and development: authorization, procurement, public subsidy, and generic substitution of drugs. ...
... Malmqvist and Munthe (2020) have identified four areas where new regulations can be introduced to encourage the pharmaceutical industry to adopt more sustainable practices in drug production and development: authorization, procurement, public subsidy, and generic substitution of drugs. In light of recent initiatives within the EU to enhance the consideration of environmental risk at the authorization level (European Parliament 2019; European Commission 2023), this paper will explore various approaches in this area and analyze the tradeoffs between different normatively significant interests that these require. 1 Interventions that regulate the market approval process can be extremely impactful, as the threat of rejection of the application can be used to apply substantial pressure on the industry, however, it also carries exceptional risk of endangering access to new medication (Nijsingh et al. 2019). For these reasons, a good deal of precaution is necessary (Malmqvist and Munthe 2020). ...
... As will become clear, such policies face a fundamental tension between individual and collective interest of the sort that is familiar from debates in public health ethics and political philosophy. 5 Specifically, they require tradeoffs between long-term public health considerations and short-term clinical ethical considerations regarding benefits and safety for patients in care (Nijsingh et al. 2019). Nijsingh et al. (2019) have identified many different stakeholders whose interests may be affected by attempts to address pharmaceutical pollution (including drug companies, physicians and other healthcare staff, as well as patients, animals and the environment). ...
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This paper contributes to the growing discussion about how to mitigate pharmaceutical pollution, which is a threat to human, animal, and environmental health as well as a potential driver of antimicrobial resistance. It identifies market approval of pharmaceuticals as one of the most powerful ways to shape producer behavior and highlights that applying this tool raises ethical issues given that it might impact patients’ access to medicines. The paper identifies seven different policy options that progressively give environmental considerations increased priority in the approval process, identifies ethically relevant interests affected by such policies, and makes explicit tensions and necessary tradeoffs between these interests. While arguing that the current European regulation gives insufficient weight to environmental considerations, the paper highlights concerns with the strongest policy options, on the grounds that these may very well endanger patients’ access to effective medication.
... Until recently, pharmaceutical manufacturing was generally seen as a no-brainer, contributing to environmental pollution on the one hand, and not forming any environmental danger from it consequence on the other hand (Babatunde et al., 2014). However, recent findings suggest the opposite: some manufacturing facilities around the world have been identified to discharge them into the environment, exceeding the previously defined levels, causing contamination (Nijsingh et al., 2019). These wastes are either disposed of in the soil or spilled with some waste on the soil, and as a result of leaching, they enter the soil. ...
... By minimizing water pollution, selective pressure on harmful microorganisms that inhabit the aquatic environment would be reduced, diminishing the spread of antimicrobial resistance and virulence genomic elements [77,78]. This comprehensive approach would not only protect the health of local communities by safeguarding the purity of the water resource but would also contribute to the preservation of antibiotic effectiveness and sustainable public health management in the long term [79]. ...
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Antimicrobial resistance has been stated to be a global health problem. In Chile, the use of antibiotics should be declared by medical prescription, but it is unknown what happens to the drugs once the treatment ends. Among the possibilities for their disposal are the trash or the drain; regardless of which scenario arises, antibiotics could accumulate in the environment, stimulating the emergence of antimicrobial resistance mechanisms and their transfer between microorganisms. Unfortunately, sometimes wastewater ends up in bodies of water, due to the dragging of elements by rain, or by the presence of illegal water discharges. In this work, shotgun metagenomics was used to elucidate the functional and microbial composition of biohazard elements in the bay of Puerto Varas City, Chile. As expected, a high diversity of microorganisms was found, including bacterial elements described as human or animal pathogens. Also, a diverse repertory of antimicrobial resistant genes (ARGs) was detected, which confers mainly resistance to macrolides, beta-lactams, and tetracyclines, consistent with the families of antibiotics most used in Chile. Similar ARGs were identified in DNA mobile elements. In addition, we tested the antimicrobial susceptibility in 14 bacterial strains isolated from Llanquihue Lake. This is the first report of the presence of genomic elements that could constitute a health problem, considering the importance of the interconnection between environmental, animal, and human health, a concept known as One Health.
... By minimizing water pollution, selective pressure on harmful microorganisms that inhabit the aquatic environment would be reduced, diminishing the spread of antimicrobial resistance and virulence genomic elements [74,75]. This comprehensive approach would not only protect the health of local communities by safeguarding the purity of the water resource but would also contribute to the preservation of antibiotic effectiveness and sustainable public health management in the long term [76]. ...
Preprint
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Antimicrobial resistance has been stated to be a global health problem. In Chile, the use of antibiotics should be declared by medical prescription, however, it is unknown what happens to the drugs once the treatment ends. One possibility is that these end up being disposed of in the trash or down the drain. In both scenarios, antibiotics could accumulate in the environment, stimulating the emergence of antimicrobial resistance mechanisms and their transfer between microorganisms. Unfortunately, sometimes wastewater ends up in bodies of water, due to the dragging of elements by rain, or by the presence of illegal water discharges. In this work, we use shotgun metagenomics to elucidate the functional and microbial composition of biohazard elements in the bay of Puerto Varas City, Chile. As expected, we found a high diversity in microbial communities, with bacterial elements described as human or animal pathogens. Also, we detect a diverse repertory of virulence and antibiotic-resistant genes (ARGs), related with macrolides, beta-lactams, and tetracyclines resistance, which are consistent with the families of antibiotics most used in Chile. Similar ARGs were identified in DNA mobile elements. In addition, we tested the AMR ability in 20 bacterial strains recovered from the Llanquihue lake. This is the first report of the presence of genomic elements that could constitute a health problem for the people who live around the Llanquihue Lake of Chile, considering the importance of the interconnection between environmental, animal, and human health, a concept known as One Health.
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Two broad approaches to environmental bioethics, what I call the "green" and the "sustainability" approach, offer very different prospects for supporting and justifying feasible policy. This chapter offers reasons to prefer the sustainability approach, although this means remaining within an anthropocentric ethical paradigm. The main reason is that the sustainability approach can combine far-reaching environmental concerns in bioethical arguments with the option of overlapping pragmatic and ideal-theoretical considerations to support feasible policy reform and practical action across all areas and regions.
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Antimicrobial resistance (AMR) – the phenomenon of microbes developing resistance to pharmaceuticals used for treating infections – is a massive systemic, global threat to public health and the effectiveness of healthcare. The ethics of AMR comprises of ethical aspects of the phenomenon itself, understanding its significance for fundamental values, and proposed actions to manage AMR, often linked to the concept of "one health". Most of this discussion has focused on rationalizing the use of antibiotics in human healthcare and farming. However, AMR has a sizeable environmental dimension that so far has mostly gone unnoticed by bioethics. This dimension comprises the role of the environment as a source for evolution of resistance as well as a transmission route, both spawned by the pollution of antibiotics and faecal matter from various sources. A bioethical analysis of AMR needs to take these dimensions into account, and doing so may potentially upset fundamental assumptions in both practical bioethics, health policy and their environmental counterparts. This chapter outlines the environmental dimensions of AMR, their bioethical significance, and some of the most obvious new ethical complexities and challenges for bioethical research made visible by broadening the scope of the ethics of AMR.
Preprint
Two broad approaches to environmental bioethics, what I call the "green" and the sustainability approach, offer very different prospects for supporting justified feasible policy. This chapter offers reasons to prefer the sustainability approach, although this means remaining within an antropocentric ethical paradigm. The main reason is how the sustainability approach can combine far-reaching environmental concerns in bioethical arguments with the option of overlapping pragmatic and ideal-theoretical considerations to support feasible policy reform and practical action.
Preprint
Antimicrobial resistance (AMR) is a massive systemic, global threat to public health and the effectiveness of healthcare. The ethics of AMR comprises of ethical aspects of the phenomenon itself, understanding its significance for fundamental values, and of proposed actions to manage AMR, often linked to the concept of "one health". Most of this discussion has focused on rationalizing the use of of antibiotics in human healthcare and farming. However, AMR has a sizeable environmental dimension that so far has mostly flown under the bioethical radar. This dimension encaptures the role of the environment as source for evolution of resistance as well as a transmission route, both spawned by the pollution of antibiotics and fecal matter from various sources. A bioethical analysis of AMR needs to take these dimensions into account, and doing so may potentially upset fundamental assumptions in both practical bioethics, health policy and their environmental counterparts. This chapter outlines the environmental dimensions of AMR, their bioethical significance, and some of the most obvious new ethical complexities and challenges for bioethical research made visible by such a broadening of the scope of the ethics of AMR.
Chapter
In recent years, the development of the “green battery” has been the focus of numerous initiatives. The current research agenda includes the replacement of environmentally dubious metals with more environmentally friendly organic compounds. Sustainable energy conserves resources and reduces pollution. This review is based on the research of various scientists and researchers who have been working on green batteries. This article aims to present an overview of the present stage of research and development on green batteries, including production, performance, and environmental impact. It also discusses the potential of green batteries to contribute to sustainable energy storage solutions for global development. This article is primarily concerned with sustainable energy storage via green batteries for global development. The need for batteries to power electric vehicles and to store energy from solar panels and wind turbines will rise as the amount of renewable energy available increases [1]. It is also true that the extraction and production of the materials used to manufacture batteries can have negative environmental impacts, including pollution and destruction of ecosystems. This is due to the increased interest of States and organizations in the need to preserve the environment and public health, which has pushed companies to reduce emissions and waste polluting the environment as part of corporate social responsibility programs which realized the importance of eco-friendly products [2]. This study intends to investigate the battery manufacturer to show how green production contributes to a green supply chain, how that chain connects with the others, and how it might improve environmental performance.
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High antibiotic releases from manufacturing facilities have been identified as a risk factor for antibiotic resistance development in bacterial pathogens. However, the role of antibiotic pollution in selection and transferability of antibiotic resistance genes (ARGs) is still limited. In this study, we analyzed effluents from azithromycin-synthesis and veterinary-drug formulation facilities as well as sediments from receiving river and creek taken at the effluent discharge sites, upstream and downstream of discharge. Culturing showed that the effluent discharge significantly increased the proportion of antibiotic resistant bacteria in exposed sediments compared to the upstream ones. Quantitative real-time PCR revealed that effluents from both industries contained high and similar relative abundances of resistance genes [sul1, sul2, qacE/qacEΔ1, tet(A)], class 1 integrons (intI1) and IncP-1 plasmids (korB). Consequently, these genes significantly increased in relative abundances in receiving sediments, with more pronounced effects being observed for river than for creek sediments due to lower background levels of the investigated genes in the river. In addition, effluent discharge considerably increased transfer frequencies of captured ARGs from exposed sediments into Escherichia coli CV601 recipient as shown by biparental mating experiments. Most plasmids exogenously captured from effluent and polluted sediments belonged to the broad host range IncP-1ε plasmid group, conferred multiple antibiotic resistance and harbored class 1 integrons. Discharge of pharmaceutical waste from antibiotic manufacturing sites thus poses a risk for development and dissemination of multi-resistant bacteria, including pathogens.
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Discharge of treated sewage leads to release of antibiotic resistant bacteria, resistance genes and antibiotic residues to the environment. However, it is unclear whether increased abundance of antibiotic resistance genes in sewage and sewage-impacted environments is due to on-site selection pressure by residual antibiotics, or is simply a result of fecal contamination with resistant bacteria. Here we analyze relative resistance gene abundance and accompanying extent of fecal pollution in publicly available metagenomic data, using crAssphage sequences as a marker of human fecal contamination (crAssphage is a bacteriophage that is exceptionally abundant in, and specific to, human feces). We find that the presence of resistance genes can largely be explained by fecal pollution, with no clear signs of selection in the environment, with the exception of environments polluted by very high levels of antibiotics from manufacturing, where selection is evident. Our results demonstrate the necessity to take into account fecal pollution levels to avoid making erroneous assumptions regarding environmental selection of antibiotic resistance.
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This chapter charts and critically analyses the ethical challenge of assessing how much (and what kind of) evidence is required for the justification of interventions in response antibiotic resistance (ABR), as well as other major public health threats. Our ambition here is to identify and briefly discuss main issues, and point to ways in which these need to be further advanced in future research. This will result in a tentative map of complications, underlying problems and possible challenges. This map illustrates that the ethical challenges in this area are much more complex and profound than is usually acknowledged, leaving no tentatively plausible intervention package free of downsides. This creates potentially overwhelming theoretical conundrums when trying to justify what to do. We therefore end by pointing out two general features of the complexity we find to be of particular importance, and a tentative suggestion for how to create a theoretical basis for further analysis.
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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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Antimicrobial Resistance: a One Health Perspective, Page 1 of 2 Abstract One Health is the collaborative effort of multiple health science professions to attain optimal health for people, domestic animals, wildlife, plants, and our environment. The drivers of antimicrobial resistance include antimicrobial use and abuse in human, animal, and environmental sectors and the spread of resistant bacteria and resistance determinants within and between these sectors and around the globe. Most of the classes of antimicrobials used to treat bacterial infections in humans are also used in animals. Given the important and interdependent human, animal, and environmental dimensions of antimicrobial resistance, it is logical to take a One Health approach when addressing this problem. This includes taking steps to preserve the continued effectiveness of existing antimicrobials by eliminating their inappropriate use and by limiting the spread of infection. Major concerns in the animal health and agriculture sectors are mass medication of animals with antimicrobials that are critically important for humans, such as third-generation cephalosporins and fluoroquinolones, and the long-term, in-feed use of medically important antimicrobials, such as colistin, tetracyclines, and macrolides, for growth promotion. In the human sector it is essential to prevent infections, reduce over-prescribing of antimicrobials, improve sanitation, and improve hygiene and infection control. Pollution from inadequate treatment of industrial, residential, and farm waste is expanding the resistome in the environment. Numerous countries and several international agencies have included a One Health approach within their action plans to address antimicrobial resistance. Necessary actions include improvements in antimicrobial use regulation and policy, surveillance, stewardship, infection control, sanitation, animal husbandry, and alternatives to antimicrobials. WHO recently has launched new guidelines on the use of medically important antimicrobials in food-producing animals, recommending that farmers and the food industry stop using antimicrobials routinely to promote growth and prevent disease in healthy animals. These guidelines aim to help preserve the effectiveness of antimicrobials that are important for human medicine by reducing their use in animals.
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Antibiotic resistance and its wider implications present us with a growing healthcare crisis. Recent research points to the environment as an important component for the transmission of resistant bacteria and in the emergence of resistant pathogens. However, a deeper understanding of the evolutionary and ecological processes that lead to clinical appearance of resistance genes is still lacking, as is knowledge of environmental dispersal barriers. This calls for better models of how resistance genes evolve, are mobilized, transferred and disseminated in the environment. Here, we attempt to define the ecological and evolutionary environmental factors that contribute to resistance development and transmission. Although mobilization of resistance genes likely occurs continuously, the great majority of such genetic events do not lead to the establishment of novel resistance factors in bacterial populations, unless there is a selection pressure for maintaining them or their fitness costs are negligible. To enable preventative measures it is therefore critical to investigate under what conditions and to what extent environmental selection for resistance takes place. In addition, understanding dispersal barriers is not only key to evaluate risks, but also to prevent resistant pathogens, as well as novel resistance genes, from reaching humans.
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Antibiotics are vital in the treatment of bacterial infectious diseases but when released into the environment they may impact non-target organisms that perform vital ecosystem services and enhance antimicrobial resistance development with significant consequences for human health. We evaluate whether the current environmental risk assessment regulatory guidance is protective of antibiotic impacts on the environment, protective of antimicrobial resistance, and propose science-based protection goals for antibiotic manufacturing discharges. A review and meta-analysis was conducted of aquatic ecotoxicity data for antibiotics and for minimum selective concentration data derived from clinically relevant bacteria. Relative species sensitivity was investigated applying general linear models, and predicted no effect concentrations were generated for toxicity to aquatic organisms and compared with predicted no effect concentrations for resistance development. Prokaryotes were most sensitive to antibiotics but the range of sensitivities spanned up to several orders of magnitude. We show reliance on one species of (cyano)bacteria and the 'activated sludge respiration inhibition test' is not sufficient to set protection levels for the environment. Individually, neither traditional aquatic predicted no effect concentrations nor predicted no effect concentrations suggested to safeguard for antimicrobial resistance, protect against environmental or human health effects (via antimicrobial resistance development). Including data from clinically relevant bacteria and also more species of environmentally relevant bacteria in the regulatory framework would help in defining safe discharge concentrations for antibiotics for patient use and manufacturing that would protect environmental and human health. It would also support ending unnecessary testing on metazoan species.
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Here we describe in detail marketing authorization and reimbursement procedures for medicinal products in Norway, with particular reference to nine novel antibiotics that received marketing authorization between 2005 and 2015. The description illustrates that, in places like Norway, with effective antibiotic stewardship policies and an associated low prevalence of antibiotic-resistant bacterial infection, there is little need for newer, more expensive antibiotics whose therapeutic superiority to existing compounds has not been demonstrated. Since resistance begins to emerge as soon as an antibiotic is used, Norway’s practice of leaving newer antibiotics on the shelf is consistent with the goal of prolonging the effectiveness of newer antibiotics. An unintended consequence is that the country has signalled to the private sector that there is little commercial value in novel antibiotics, which may nevertheless still be needed to treat rare or emerging infections. Every country aims to improve infection control and to promote responsible antibiotic use. However, as progress is made, antibiotic-resistant bacteria should become less common and, consequently, the need for, and the commercial value of, novel antibiotics will probably be reduced. Nevertheless, antibiotic innovation continues to be essential. This dilemma will have to be resolved through the introduction of alternative reward systems for antibiotic innovation. The DRIVE-AB (Driving re-investment in research and development and responsible antibiotic use) research consortium in Europe has been tasked with identifying ways of meeting this challenge.
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Using simple economic reasoning, this book analyses a broad range of global challenges including global warming, ozone shield depletion, acid rain, nuclear waste disposal, revolution dispersion, international terrorism, disease eradication, population growth, tropical deforestation, and peacemaking. These challenges are put into perspective in terms of scientific, economic, and political considerations. Many of these contingencies are shown to be solvable without much explicit coordination among nations. Although there is no panacea to these challenges, much can be done to tailor solutions. This book is intended for a wide audience drawn from the social sciences, including economics, environmental studies, political science, sociology, and public policy. It should also interest the general reader who wants to learn about global challenges.
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Pharmaceutical manufacturing can lead to substantial discharges of active pharmaceutical ingredients into the environment, with local consequences to the environment and, in the case of antibiotics, potentially global implications in terms of increasing risks for resistance development. In this study, we used Swedish sales data for pharmaceuticals combined with data on the origin of the active ingredients to determine if price pressure and generic substitution are related to the estimated general environmental performance and the perceived corruption levels of the production countries. In line with the general perception, India was the largest producer of generics, while Europe and the USA dominated for branded products. We found that the price and environmental performance index of the production countries were linked, but that this relationship was largely explained by whether the product was original or generic. Although this relationship would allow buyers to select products that are more likely to originate from countries that, in general terms, have better pollution control, it lacks resolution. We conclude that to better allow consumers, hospitals and pharmacies to influence the environmental impact of their product choices, there is need for regulation as well as transparency in the production chain. To this end, emissions from manufacturing need to be measured, allowing for control and follow-up on industry commitments towards sustainable manufacturing of pharmaceuticals.