I. 'Role of Public Health professionals and the Community in the

Control of Antibiotic Resistance'- Report of a panel discussion

Panelists

Mira Shiva, Otto Cars, Anurag Bhargava, Cecila Stalsby Lundborg,A.J. Tamhankar,

Sujith J Chandy, Ravi Narayan.

AIDAN- Delhi, STRAMA – Uppsala, Sweden, JSS- Bilaspur , IHCAR –Karolinska

Sweden , R.D.G.M. C- Ujjain ,& Acharya & Marathe – C Mumbai, CMC - Vellore,

CHC- Bangalore..

Introduction to the theme- (Dr. Mira Shiva)

Over the years medicines have been introduced in community health programs and they have found markets in remote areas, unregulated and unsupervised. While they have saved lives when rationally used they have also resulted in serious adverse affects which have unfortunately remained unmonitored. The adverse affect of irrational use of antibiotics has not only created problems for individual patients but also for the community. Emergence of drug resistance for many of the communicable diseases have been noted. Among the significant ones have been Malaria, T.B., Typhoid etc. Over thousand deaths took place due to emergence of resistance of the common antibiotics against Bacillary Dysentery (Shigella Shega) in Bengal in 1980s which rapidly spread to other areas. Continued sales of combinations of antibiotics were responsible for emergence of drug resistance. Extended Public Interest litigation resulted in banning of some of these e.g. Streptomycin Penicillin combination and also Chloramphenicol Streptomycin combination. Rational Use of antibiotics is essential to prevent antibiotic

resistance as a public health problem. And for this it is essential to 'know your medicine', antibiotics in this case as well as 'now your body' and 'know your health problems'. Improving health literacy and health awareness has to go side by side with improving awareness about medicines. The cost of antibiotics has definitely contributed to irrational drug use and also emergence of antibiotic resistance. Lack of knowledge about the prevailing health culture and failure to communicate in a patient-friendly manner about health and disease and role of medicines in disease care especially where anti-microbials and living organisms are concerned has resulted in overuse, misuse and under use of medicines. Decreasing immune status of the human body and increasing vulnerability to infection due to poor nutrition, must also be addressed when addressing the issue of emergence of drug resistance.

The Global Challenge- (Prof. Otto Cars)

The growing phenomenon of bacterial resistance, due to use and abuse of antibiotics and the simultaneous decline in research and development of new drugs, is now threatening to take us back to a pre-antibiotic era. Although the essential components of control of antibiotic resistance have been well known for long, there has only been limited success in changing policies and efficiently responding to the problem. However, national campaigns have been initiated in some countries with significant effect on the antibiotic consumption level.

To reach the concerted action on antibiotic resistance, all levels in society need to be involved. In Sweden, a national programme, Strama, was implemented more that 10 year ago and is now integrated in the health system and supported by the Government. Through the County Medical Officers for Communicable Diseases regional Strama groups are established in every county. Treatment guidelines, feedback to prescribers and patient information leaflets are examples of multiple activities and interventions that are being used to address the irrational use of antibiotics e.g. for viral infections and otitis media On the national level, the total antibiotic use has been reduced by more that 20%, in children with 40% without measurable negative consequences. Several large diagnosis-prescription studies have been performed both in outpatients and in hospitals. (for further details see paper, section -II following this report)

Antibiotic Resistance: A view and some lessons from a Community

Hospital. (Dr. Anurag Bhargav)

A review of data and perspectives from the frontline of healthcare, from a program in rural Chattisgarh which included primary and secondary care facilities and which cater to the poor and the underserved, in one of India's rural areas, shows a situation which is both alarming and unexpected. This situation includes drug resistance on isolates from urinary tract infections, tuberculosis, and falciparum malaria and has serious implications for treatment and control of communicable diseases, both at individual and programmatic level.

Such data is usually under-represented in academic and policy discussions. The crisis of drug resistance should be placed always within the context of the larger crises of public health and healthcare in India. A response to this problem requires a major shift away from a fragmented, germ and disease centered approach. There is a pressing need for attention to the foundations of public health, for strengthening of primary care, for education and regulation in the prudent use of antibiotics, for infection control measures in healthcare settings, if this public health disaster is to be addressed with any efficacy. ( for further details see short paper, section –III following this report)

Information and Interaction – Influencing Provider and Consumer Antibiotic Behavior (Prof. Cecilia Stalsby Lundborg )

Antibiotics are life-saving and commonly used drugs. Antibiotic use is probably the most important factor in resistance development. It is of outmost importance that antibiotics are accessible and used when needed, but used as little unnecessarily as possible for reasons of resistance development, adverse drug reactions and costs. Influencing provider and consumer behavior in relation to antibiotic use is a complex process involving knowledge, but which also involves a number of other factors such as attitudes, social norms, socioeconomic conditions, peer pressure, experiences etc. When designing projects or programs for change it is often useful to consider theories or models of behavior change. For professionals Schöns’ model, emphasizing “knowledge in action” and “surprise” as important drivers for professional change is useful. The “Stages of change model”, including the stages; pre-contemplation, contemplation, preparation, action and maintenance has been used in contexts of influencing professionals and lay-

people. People in different stages of change are susceptible to different intervention strategies. Further, concepts are often perceived in a different ways. It can never be assumed that everyone understands a message in the same way. The conclusion is that just providing correct knowledge regarding antibiotic resistance to providers and consumers is not sufficient although a pre-requisite for change in a desired direction. The process requires a more complex response to change behavior affected by various other factors. (for further details see short paper, section - IV following this report)

Location specific Integrated Antibiotic Resistance Management Strategy (L I A R M S) Dr. A. J. Tamhankar

It is generally observed that, though not necessarily in thinking but in practice, `control of antibiotic resistance` remains mainly in the realm of human use related clinical/hospital issues. A very large area of antibiotic presence, does not get the attention it deserves, when antibiotic resistance management is thought of. For example, non-human use of antibiotics ( veterinary use) and presence of antibiotics in the environment due to contamination by human activities ( hospital wastes & effluents of the antibiotic manufacturing units . Up to 50% of antibiotics produced is consumed in non-human use. Very little of the antibiotics taken by humans and animals for treatment is metabolised; the remnant is released in environment unchanged. These environmental pools form huge breeding grounds for resistance development, which if left unattended can nullify all the efforts directed mainly considering human use of antibiotics. The `total environment` situation varies in every setting and needs to be addressed with location specific concerns taking into account all aspects. For this a Location specific Integrated Antibiotic Resistance Management Strategy (LIARMS) needs to be evolved in which human and veterinary health professionals, the NGOs and the community at large have a big role to play to ensure that all foci of antibiotic resistance development are accounted for and are paid the attention they deserve. (for further details see short paper- section- V, following this report)

Understanding the complexity of the determinants of antibiotic

resistance. (Dr.Ravi Narayan)

From the panel discussion so far we begin to understand the complexity of the problem of the antibiotic resistance. We need to appreciate different levels of factors and determinants. At the most primary level (in the interaction between the provider and the

consumer) the determinants are:

• Irrational use and abuse of antibiotics. • Over use and Misuse • Inadequate provider education • Lack of patient education • Problem of combination and substandard drugs • Variation in patient level of nutrition and immunity • Irrational consumer behavior. • The problem of cost.

At the next level which could be termed, the public health level, the determinants

would include

• Inadequate treatment guidelines. • Inadequate infection control • Lack of monitoring and surveillance • Decline in research funds • Inadequate control of veterinary use • Environmental pollution as contribution to reservoir of resistant germs • Inadequate primary health care. • Inadequate public health systems.

Both these levels of determinants acting at clinical and public health level are

further complicated and affected by health policy determinants which include

• Economic constraints • Decreased investment in social sector including health • Commercialization of health care and social security. • International trade policies including WTO and IPR affecting cost and availability

of drugs including antibiotics. • New economic policies. • Increase in social inequalities and marginalization due to flawed development

policies • Unsustainable development policies including displacement • International travel

Any effort at tackling this problem will require a deep understanding of this complexity and an evidence based monitoring of each of these factors and their contribution to the problem before an action plan can emerge at a local, state or national level.

Some reflections on policy and action -The way forward in India (Dr. Sujith

J Chandy), As was mentioned by the previous speakers, the world is fast hurtling to a post antibiotic era where a majority of the antibiotics will not useful due to antibiotic resistance. This scenario which is already upon is, is largely due to inappropriate use of antibiotics. There are a number of factors which contribute to this misuse. These include:

• The public - They have poor knowledge of illnesses. They do not know that a common cold is due to a viruses, and thus do not need antibiotics. They are ignorant of what an antibiotic is, and the consequences of irrational use.

• The Doctors - They are often pressurized to give antibiotics for fear of losing clientele. Patients often cannot afford a full course of antibiotics. Inadequate investigational facilities promote combination antibiotics and defensive medicine.

• The Pharmacists - They often give antibiotics without a prescription. Business rather than science often motivates this action

• The industry and medical representatives - They often push irrational drug use more than any other player. After all, ‘money makes the world go around’! Doctors and pharmacists are open to incentives for prescribing and dispensing particular brands.

• The Regulators - Governmental regulations on antibiotic use in India are minimal. Policies put in place are not strictly implemented. Neither are there sufficient penalties for irrationally prescribing an antibiotic drug.

Antibiotic

Resistance

Inadequate treatment guidelines

Inadequate infection control

Inadequate control of Veterinary

use

Lack of Monitoring/Surveillance

Environmental Pollution as reservoir

Inadequate Primary Health Care

Inadequate Public Health Systems

Decline in

Research funds

Consumer Behavior

Lack of patient

education

Inadequate provider education

Cost Over use/ misuse

Irrational use/ abuse

Malnutrition /Immunity

Combination \substandard

drugs

Understanding why? INEQUALITY

MARGINALISATION NEW ECONOMIC POLICIES

(Liberalization, Privatization, Globalization)

ECONOMIC

CONSTRAINTS

COMMERCIALIZATION

OF HEALTH CARE

DECREASED INVESTMENT IN SOCIAL SECTOR

INTERNATIONAL TRADE: WTO/IPR

INTERNATIONAL

TRAVEL

UNSUSTAINABLE

DEVELOPMENT AND

DISPLACEMENT

Source: CHC, SOCHARA

• Other stakeholders - Their contribution to irrational antibiotic use is far from minimal. Farmers, overuse antibiotics for both animal and agricultural purposes. This leads to cross resistance for humans. Complementary medicine specialists and quacks also use antibiotics although they have no expertise in it.

It can be concluded that the whole society is involved in killing the antibiotic and increasing antibiotic resistance. Therefore it is up to us, the society, to save the rational antibiotic movement. Strategies need to be multidimensional in method and multipartner in involvement in order to be executable, sustainable and successful. It could then be used to effect a lasting change to lead to rational use of antibiotics and lower levels of resistance. The mechanisms and players who need to be involved are:

1. The public – • Make the public aware of illnesses, features and drugs needed. Knowledge is

power, power to save! • Knowledge of the role of antibiotics and sensitization to the concept of antibiotic

resistance should be disseminated • Knowledge needs to be disseminated attractively, in simple language and spread

widely through media. • Schools, women’s groups, and leaders should be made aware of medicine misuse

and its consequences. • Involve leaders of communities and opinion leaders • Role of NGOs and media in sensitizing the public should be properly explored 2. The Prescribers – • Bring together doctors in various forums • Present the facts, for example graphs on resistance and correlation to antibiotic

overuse. Understanding is often the first step to action and reaction. • Allow them to ventilate problems in antibiotic prescribing. Use that information

in planning of interventions • Involve them in making guidelines with evidence based input. Participatory

decisions will have more compliance. 3. The Dispensers - • Pharmacists can act as a bridge between public and doctors! They should not be

left out. After all, many patients go to chemist shops only. Discussions to bring out their problems can be useful.

• Give them continuing education to keep them in tune with medical advances • Present facts on resistance and antibiotic use and discuss issues of ‘over the

counter’ antibiotics • Issues of business vs. science vs. social responsibility should also be discussed • Policies such as an agreement to delay antibiotics, give simple drugs first and less

combination antibiotics can be discussed

4. The Regulators -

• Government regulations should be reviewed and made with a view towards implementation

• Government regulations should take to task companies which misinform doctors. The role of incentives in promoting irrational use needs to be studied.

• Regulation for drug waste and disposal needs to be implemented to prevent water contamination

• Funding for research into existing resistance & use issues and its impact on overall health and economic implications is important. This will also help to involve the academia

• Evidence in a truthful but intelligent way on the harm and the costs irrational drugs use is causing may spur the government to change policies. Public pressure also plays a part. Government should put antibiotic resistance and misuse on its priority list – as a public health emergency

• Public, NGO and activist pressure should play an important role in influencing

government reaction & regulation

5. The Pharmaceutical Industry –

• Strict guidelines and penalties on unethical promoting, advertisement and incentives are important and it the various companies should be compliant with these guidelines

• A joint agreement to give proper, scientific information to health professionals would be a good initiation

• At the same time it is important to engage the industry on the issue of antibiotic resistance. On of the difficulties is the paucity of active research and development on new antibiotic molecules. Incentives by the government for research and development on newer antibiotics should be prioritized

• Newer antibiotics which favor compliance should be thought off as well as a review of cost and price control – this may encourage completion of course.

6. Other stakeholders –

• Other players such as agriculturists and livestock carers need to be educated and made aware of the consequences.

• Antibiotic access should be restricted & use regulated based on scientific principles

• Complementary medicine specialists need to use medicine of their own specialty

rather than allopathic antibiotics • Complementary medicine specialists need to be restricted and educated on

allopathic therapy. • Quacks use allopathic drugs as concoctions. In India a significant number of the

public visit quacks. Hence they need to be identified, involved, and educated in order to make them aware of the implications and consequences. Regulation alone may not work in practice.

Tackling antibiotic resistance is a multi sectoral, and multi dimensional challenge. As outlined above each of the stakeholders can play a part in leading to rational use of

antibiotics. But they can play their part only if the ‘whole society’ is involved. What we

urgently require is a commitment by providers, consumers, academics, researchers,

policy makers and health and development activists, civil society and industry and

every one else who can contribute to the solution- to work together in a campaign or

movement mode to tackle the problem by action at various levels. The components of

this campaign would include gradually, most of the following -

� Promoting rational prescribing practices

� Controlling combination and substandard drugs

� Controlling over the counter sales

� Cost control

� Strengthen Provider/prescriber education

� Promoting rational consumer education

� Strengthening multifaceted approaches for behavioral change

� Strengthening nutrition

� Antibiotic treatment- guidelines and schedules

� Strengthening infection control in health care institutions

� Improving the surveillance of resistance in hospital/health care

� Promoting more research on the problem

� Improving hospital waste disposal

� Promoting better guidelines for Veterinary use

Antibiotic

resistance

Antibiotic treatment guidelines/ schedules

Strengthening infection control in health care

institutions

Veterinary Use

Guidelines

Improving

surveillance

Hospital waste

disposal.

Strengthening Primary Health Care

Strengthening Public Health Systems

Promoting more

research on the problem

Promoting rational consumer education

Multifaceted approaches for

Behavioral change

Provider / prescriber education

Cost control

Controlling OTC

Rational prescribing

Strengthening Nutrition

Controlling combination

drugs

What can be done….

Local/national/regional global action

People’s need oriented economic/trade policies

Political

Awareness and

support

Increased investement in health/ nutrition/social welfare/ education

Sector

Countering commercialization of health care

Equitable

touris

m optio

ns

Tackling Environ mental

challenge/ LiARMS

Safe drin

king

water, s

anitatio

n

Source: CHC, SOCHARA

� Strengthening primary health care

� Strengthening public health systems

� Tackling environment challenge through L I A R M S

� Increasing investment in health and social sector

� Countering commercialization of health care

� Safe drinking water and sanitation

� Peoples need oriented economic and trade policies

While evolving such a campaign we should involve and link with existing and active

health networks and movements to increase synergy and convergence.

Its therefore up to us to act and act fast. The consequences of antibiotic resistance can

affect all of us and are already upon us whether we like it or not!

By rationally using antibiotics, the society can save the society from destroying the

society!!

Can we rise up to the challenge, and save the antibiotics that save us!

II. The Global Challenge and the Swedish Experience

Prof. Otto Cars

STRAMA, Sweden

III. Antibiotic Resistance: A view and some lessons from a Community Hospital

Dr. Anurag Bhargava

Jan Swasthya Sahyog, Bilaspur

IV. Information and Interaction – Influencing Providers’ and

Consumers’ Antibiotic Behaviour

Cecilia Stålsby Lundborg PhD

Professor in health systems research, Nordic School of Public Health,

Associate professor, Division of International Health, IHCAR, Department of Public

Health Sciences, Karolinska Institutet, Sweden

Visiting professor in Pharmacology, R.D. Gardi Medical College, Ujjain, M.P., India.

cecilia.stalsby.lundborg@ki.se

Introduction

Antibiotics are life-saving drugs. They are also one of the most commonly used drugs in

the health system. Antibiotics are used throughout the health system with or without

professional guidance, often without appropriate diagnosis being made prior to their use

(Nordberg et al 2005; Sihavong et al 2007; Lan et al 2008). Antibiotics are in many

settings prescribed or dispensed by health care workers or others without any or with

limited education.

International as well as national strategies for control of antibiotic resistance often

recommend education for health care professionals, including e.g. doctors, pharmacists

and nurses and the public (WHO 2001, Okeke et al 2005, Mölstad et al 2008). Implicit in

such campaigns are that they beside providing information also should lead to behaviour

change. Interventions are however more likely to be effective if they while aiming at

changing behaviour also include appropriate theories on behaviour change (Finch et al

2004). Further they need to acknowledge that people have various understandings of

concepts such as e.g. “antibacterial resistance”. Qualitative studies show wide variations

in views on various phenomenon in health care (Dall’Alba and Sandberg 1996, Stålsby

Lundborg et al 1999a). The problem of resistance is not different. Recent studies among

Swedish physicians shows variations in views on antibacterial resistance from seeing it is

non-important in everyday practice or in the long-term perspective to seeing it a serious

threat today as well as in the future and nationally as well as internationally (unpublished

observations). Variations in views among care-takers regarding health seeking behavior

in relation to child infections is seen in Vietnam (Hoa et al 2007). It is likely that similar

variation in views of the problem of antibacterial resistance and treatment of infections

exists in all settings and among professional as well as consumer groups. Such variations

in views need to be understood in order to design successful interventions aiming at

changing behavior.

The aim of this paper is to present some theories for changing provider and consumer

behavior in relation to antibiotic use. Further to give some examples of successful

methods for interventions in this area.

Behavioral change theories and their application for behavioural

change of providers and consumers

There are many different theories on behaviour change, why it happens, how it happens

and various types of factors which influence the change. Below some of these theories

are described in short and related to change in antibiotic behaviour.

Focus on providers

The traditional model of continuing medical education (CME) now often referred to as

continuing professional development (CPD), consists of “information passing”, which

has been described as pouring or pot-filling from “teacher” to “student”. The sole

application of such a model has been criticised e.g. by Coles and Holm (1993) as such a

linear communication is not considered optimal in the communication with providers.

The providers’ experiences and expectations (Schön 1987) as well as their values and

norms (Ajzen 1988) are important to incorporate or address in educational programs.

Educational models, encouraging reflection on practice, the use of feedback and small

group learning including discussions are more likely to change behaviour. Learning based

on experiences and the necessity to link new knowledge or new ways of behaviour to

already existing practises has been stressed among authors writing on professional

learning (Schön 1983, 1987, Mann 1994, Ramsden 1992). Schöns’ model, emphasizes

“knowledge in action” and “surprise” as important drivers for professional change. The

need to link theory to educational interventions aiming at changing antibiotic behaviour

has been emphasized (Stålsby Lundborg 1999b; Finch et al 2004).

The “stages of change theory” or “the trans-theoretical model” was originally developed,

describing the process a person goes through when giving up drinking and later smoking

(Proschaska et al 1992). However, the five stages in this theory, pre-contemplation (not

thinking about change), contemplation (considering change, but not ready for action),

preparation (planning for change), action (change is initiated) and maintenance of

changed behaviour, could equally well be applied for a change in prescribing behaviour

in general (Thomson et al 2004; Shirazi et al 2008) and antibiotics in particular (Finch et

al 2004). Persons in different stages of change are susceptible to different intervention

strategies.

Fig 1. From IMPART study cited by Finch et al 2004.

Change in prescribing behaviour could also be related to the concept of the prescriber’s

”evoked set” of drugs (Denig 1994) and the process it takes to introduce a new drug

within the evoked set. The evoked set could be compared to pre-set choices in a

computer. Choosing between one of these pre-set alternatives is easy, while it is very

difficult to choose something which is not among these alternatives. From this theory it is

also seen that it is easier to substitute one drug with another one, rather than abstaining

from prescribing.

The so-called Precede/Proceed model was developed for adult health education programs

(Green et al 1988). In this model, predisposing, enabling and reinforcing factors are

discussed in relation to behavioural change. Predisposing factors are knowledge and

attitudes which promote or inhibit a specific behaviour, such as knowledge about

resistance. Enabling factors are individual or organisational factors that facilitate an

action e.g. the availability of easily applicable treatment algorithms for various infectious

diseases. Reinforcing factors are rewards or punishments that follow a behaviour. For

example, when a new behavioural pattern is tried, e.g., prescribing in a different way than

before, reinforcing factors, could be positive comments on the new therapy by peers or

positive feedback from patients. Such reinforcing factors are often necessary to establish

the new behaviour (Tamlyn and Battista 1993, Soumerai and Lipton 2002). These kinds

of factors are related to motivation and overcoming barriers to change, as described by

Gray (1997).

The relationship between the person, the behaviour and the environment and an emphasis

on self-directed learning as a natural process was described in the “Social learning

theory” (Bandura 1977). Further, awareness of a problem or a need on the part of the

prospective adopter of a new technology was seen as important in a study on physicians’

views of change processes (Geertsma et al 1982). Common themes in all these models

are the importance of other persons for inducing change and that change is a multi-

factorial event, complex to elicit.

”Academic detailing” is a concept introduced in the beginning of the 80s in the area of

educational outreach to improve drug prescribing (Avorn and Soumerai 1983).

”Academic detailing”, originally based on the social marketing approach, includes

elements of most of the above mentioned theories. Theories on adult learning are,

however, not explicitly addressed. ”Academic detailing” has been summarised as follows

(Soumerai and Avorn 1990) (i) assessment of motivation for current practices and

barriers to change, (ii) focusing on specific physician categories, (iii) developing

objectives for the education, (iv) establishing credibility (v) encouraging participation,

(vi) using concise educational material, (vii) repeating key messages and (viii) ideally

providing reinforcement through more than one visit.

Academic detailing is often considered among the most effective ways of changing

prescriber behaviour in relation to antibiotic behaviour in ambulatory care (Schaffner et

al 1983; Arnold and Strauss 2005). In general higher complexity models often refereed to

as multifaceted models seem to be effective in ambulatory care (Stålsby Lundborg et al

1999b; Arnold and Strauss 2005). In hospital care several types of interventions was

shown effective (Davey et al 2005). However it is pointed out that the design of the

studies as well as the selected outcome measures may affect the possibility to interpret

and generalize the results.

It is important to note that educational interventions are relatively easy to implement in

all kinds of settings as they can use local resource persons, which is relatively less costly

(Santoso et al 1996; Okeke et al 2005). Interventions or intervention models applicable

to educated professionals can also, in modified versions, be implemented for less

educated providers (Chuc et al 2001; Stenson et al 2001).

Special comments in relation to consumers

Consumers are of course in many ways similar to providers when it comes to changing

behavior and all the theories mentioned above are more or less applicable to consumers

as well. The trans-theoretical or “stages-of change model” (Proschaska et al 1992) was as

pointed out above originally developed for changing lay-peoples behaviour.

There are some features of consumers that need to be pointed out. First they can be

divided into three groups, community members, not currently sick, patients and parents.

These three groups need partly different types of messages. Also within the groups there

are wide variations in knowledge and previous experiences as well as in socio-economic

background and other variables such as language. Further, they are many more as

compared to professionals. Thus mass-communication strategies are more important. TV

supported by radio, posters for health-facilities, leaflets etc are often used in combination

(Finch et al 2004, Sihavong et al 2006).

There is an intricate web of interactions within the consumer group as well as between

the professional and consumer group. Providers’ perceptions of patients’ demand for

antibiotics as well as an actual demand by consumers of antibiotics influences antibiotic

prescribing and dispensing. Selfmedication with antibiotics is an international issue

(Grigoryan et al 2006, Sihavong et al 2006, Nyazema et al 2007) which increases access

to antibiotics but also impose an increased risk of unnecessary use of antibiotics, a

tradeoff which needs special attention. One possibility in area with low access to formal

health care providers is to acknowledge their importance and educate informal providers

or non-physicians regarding e.g. antibiotic use (ADDOs project Tanzania).

Conclusion

Changing providers’ and or consumers’ behavior is a complex process. Providing

knowledge in the form of evidence is in itself not enough even though it is in most cases

a pre-requisite for acquiring a wanted behavior. In all cases, as clear messages as

possible, needs to be given to avoid misunderstanding. The application of theories of

behavioral change in intervention studies as well as in implementation of interventions is

an important strategy to attain successful changes in outcomes. Studies evaluating the

effectiveness of various types of interventions are needed. However, as in all

implementation research, the context is of great importance whereas local validations of

interventions will always be required.

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V . Lo c a t i o n Sp e c i f i c I n t e g r a t e d An t i b i o t i c

R e s i s t a n c e Mana g emen t S t r a t e g y ( L IARMS)

Ashok J. Tamhankar

R.D. Gardi Medical College, Ujjain

and N.G. Acharya & D.K. Marathe College, Mumbai

Antibiotics are used to take care of the bacterial infections in the area of human and

animal health, in agriculture, aquaculture, food preservation etc. They are also used in

animal growth promotion. While the human use of antibiotics gets maximum recall that it

deserves, uses other than in humans do not get the attention they deserve, despite the fact

that as per WHO estimate half of the antibiotics produced globally are put to uses other

than human use and of this, utilization in farm animals constitutes a very large share

(WHO, 2002).

Once the antibiotics are enclosed in the packages in which they are put during

manufacture; various human activities result in the contamination of the environment by

antibiotics. For example they get into the environment through excretion by humans and

animals (Brown et al. 2006), through disposal of unused antibiotics and as waste from

pharmaceutical plants (Guardabassi et al.1998). Not all of the antibiotics used by humans

and animals are metabolized by reactions like hydroxylation, cleavage or glucuronation, a

considerable amount is excreted in the environment via urine and feces, which gets mixed

with receiving waters (Yang and Carlson 2004). A number of investigators have reported

up to several microgram / litre levels of pharmaceuticals including antibiotics in different

environmental niches like municipal sewage, sewage treatment plants, surface and river

water, groundwater, drinking water, sludge, manure, agricultural soil, coastal waters and

sediments etc (Daughton and Ternes 1999; Hartmann 1998,1999; Hirsch et al. 1999;

Huang et al 2001; Lindberg et al. 2004). Antibiotic residues may also be found in food

products (Dutta, Barua and Dutta, 2003). In India, Larsson, Pedro and Paxeus (2007)

have reported presence of antibiotics in waters receiving waste from pharmaceutical

plants near Hyderabad. They have reported concentration of the most abundant drug,

ciprofloxacin to be exceeding levels toxic to some bacteria by over 1000-fold (up to

31,000 µg/L).

It need not be brought out very elaborately that there are always enough bacteria in

various biotic and abiotic environmental niches mentioned earlier and their interaction

with the antibiotics leads to creation of foci of antibiotic resistant bacteria in the near and

far environment of human beings. Studies in India show high levels of antibacterial

resistance in bacterial samples from humans (Verma et al., 2000, Jain, Kumar and

Awasthi, 2005) and also from samples from milk, cow stool, beef as well as poultry

(Dutta, Barua and Dutta, 2003; Khan et al., 2002, Saxena, Singh and Lakhchaura, 2005).

Resistant bacteria have also been reported from various other environmental niches (Ash

et al. 1999; Watkinson et al. 2007). Use of animal growth promoters also leads to

development of resistance.

The worrying aspect of antibiotic resistance is that development and spread of resistance

in bacteria can get transferred from pathogenic to non-pathogenic bacteria and vice versa

and also frombacteria from one niche to another niche and this has been reported very

specifically in case of bacteria infecting farm animals whose resistance can further get

transferred to those infecting humans (Angulo, Nargund and Chiller 2004; Kolawole and

Shitlu 1997; Lu et al. 2002; Molbak 2004; Simango and Rukure 1991; WHO 2001). In

addition to their impact on resistance development, antibiotics may also be implicated for

genotoxicity.

It is a matter of global public health concern that pathogenic bacteria have developed

resistance to antibacterials and it is more worrisome because it leads to increased deaths,

prolonged treatments and economic losses (Melander et al. 2002; Coast and Smith 2003;

WHO 2001, 2004, 2007a). Therefore this issue has been put on the global agenda time

and again calling for determined actions (WHO, 2001, 2005, 2007b).

In tropical climate the impact of such resistant organisms could be highly significant in

the spread of antibiotic resistance and we could be sitting on a `time bomb ticking very

close to explosion`. To counter this situation, development and implementation of

suitable interventions to minimize resistance development will be of utmost importance.

Antibiotics are life saving drugs and their use is essential to save human lives, however

effective management and appropriate use strategies at every level can reduce the

problems that may occur due to development of resistance in pathogenic bacteria. A very

simplistic and effective approach is to focus on interventions that can optimize the use of

antibiotics in every setting so as to reduce the amount of antibiotics entering the

environment. This approach will no doubt reduce the antibiotics coming into the

environment but it will not altogether stop the environmental contamination.

To develop suitable antibiotics resistance management strategy it is essential to delineate

all the places of antibiotic existence such as places of manufacture, places of use,

antibiotic providing agencies, all sources of antibiotic release into environment, agencies

involved in management of all of these, pressure groups which can help implement

antibiotic resistance management strategy etc. Taking all these stakeholders into account

an antibiotic resistance management strategy can be planned and implemented, keeping

in mind that non pharmacological preventive measures, especially keeping of good

hygiene is acknowledged as highly important in human medicine as well as in veterinary

medicine (WHO 2001).

An excellent example of antibiotic resistance management exists in Europe where growth

promoters were banned by various nations in the European Union, which brought about a

significant reduction in antimicrobial use in livestock without major negative impact on

animal health, food safety or economic aspects (WHO 2002). But this is a very small

area in the overall picture and a strategy which could have taken into account several

aspects of antibiotic existence in environment would perhaps have resulted in a dramatic

and long lasting impact.

Hospitals are the direct source of both resistant bacteria as well as unmetabolized

antibiotics as these are mostly prescribed through hospitals. Antibiotics mixed with

regular municipal wastewater can contaminate receiving surface and ground water as

well (Rooklidge 2004). About 26500 million litres of wastewater is generated by cities in

India out of which only about 25% gets any treatment and it is not known whether the

treatment that is given removes antibiotics or not.

We (Cecilia Stålsby Lundborg, A.J. Tamhankar and APRIAM project group-

unpublished observations) studied antibiotic residues in hospital wastewater in a town in

western India in the project “Antibiotics as environment pollutants and resistance in

waters in rural India - relation to antibiotic management” funded by Swedish Research

Council and found abundant antibiotics contamination (ceftriaxone, ciprofloxacin,

ofloxacin , levofloxacin, norfloxacin, sulphamethoxazole, tinidazole, metronidazole) in

hospital wastewater -the lowest amount being that of metronidazole 2.5 µg/L and the

highest amount being that of ciprofloxacin 236.6 µg/L. Further, the Escherichia coli

present in this water were also resistant to several antibiotics like amoxicillin+clavulanic

acid, ceftriaxone, ceftazidime, cefotaxime, cefuroxime, cefixime, amikacin, gentamicin,

nalidixic acid, ciprofloxacin, gatifloxacin, levofloxacin, norfloxacin, lomefloxacin,

sparfloxacin, imipenem, nitrofurantoin. This indicates that antibiotics and resistant

bacteria are entering into Indian water sources. This indicates an emerging problem of

antibiotic resistance in bacteria in non-clinical samples such as water and wastewater in

India.

A typical flow path of antibiotic existence is- production/manufacture facility to

distribution channel (dealers, retailers, providers) to a typical use area such as human

and/or veterinary medicine utilization to waste to manure/sewage to soil/sewage

treatment plant to surface water/sediment to ground water to potable water. Since every

niche of these could also posses bacteria, the exposure of bacteria in all these niches can

lead to existence of resistant bacteria in them. Thus without our realization we have all

around us repositories of antibiotics and antibiotic resistant bacteria. Although various

antibiotics have varying fate in the environment, for example aminoglycosides and β-

lactams are least persistent in the environment (Huang et al. 2001) and Sulfonamides and

fluoroquinolones are the most persistent in the environment followed by macrolides and

tetracyclines (Jacobsen et al. 2004), still for various periods of time they persist in

environment.

The foregoing information brings to our notice that antibiotic resistant bacteria and their

`reason de etre` the antibiotics, are present at several locations other than the hospital and

clinical environment where most of the interventional strategies get focused. These

locations may vary from place to place i.e. they will be `location specific` and will have

locational characteristics. Therefore a prudent resistant management strategy will be to

account for all the places of existence of antibiotics and antibiotic resistant bacteria in a

target area and focus interventional strategies towards all of them simultaneously. If this

is not done, while we are attempting to solve the problem at one/some compartment(s) of

the `total environment`, the resistant bacteria breeding in the remaining compartment(s)

of the `total environment` will form a supply chain of resistant bacteria, sometimes

failing our efforts and at other times giving an illusion of short term satisfaction. Thus in

the management strategy the term `location` will be context specific and may apply to a

geographical location(s), and/or to a location of antibiotic reservoir and/or to a location of

repository of antibiotic resistant organisms. Further, when attempting to develop such a

strategy all imaginable and available components/solutions should integrated to form a

`total solution`. Such an integrated strategy could then involve any and all types of

interventions physical/mechanical/chemical/biological and should also involve all

available prophylactic and cure practices from traditional as well as modern medicine.

The location specific integrated resistance management strategy also needs to involve all

relevant stakeholders to make it successful. Here the public health practitioners, the

NGO`s and community leaders have an important role to play as pressure groups as they

can only see to it that no stakeholders renegade from the commitment once it is made.

We (Tamhankar, Cecilia Stålsby Lundborg and others, unpublished observations) studied

the knowledge and awareness of villagers/towners and their medical and veterinary drug

providers in a project funded by Sida/Sarec and found that the awareness at every level

regarding antibiotics use and resistance development is highly satisfactory and there is a

highly receptive environment for campaigns explaining the correct methods of use of

antibiotics and we feel that the time is ripe for developing and implementing location

specific integrated antibiotic resistance management strategy.

Acknowledgement: The author is grateful to all the collaborators in various ongoing

projects, the authorities, the funding agencies and colleges he is attached to for giving all

the needed cooperation.

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Additional resources on Antibiotic resistance

• Websites

Visit ReACT: http://www.reactgroup.org/dyn/,3,,.html

Visit STRAMA; http://www.en.strama.se

• Video- 'Antibiotic Resistance for Idiots'-

A short video for popular education raising the following questions

Could antibiotic resistance be a metaphor for and even closely related to the imbalances we see in use of other valuable resources around the world today? When we talk of resistant bacteria we also need to ask which area of human intervention on Earth is not producing its own resistance. In fact if we consider our planet to be a living creature then global warming can also be interpreted as the Earth developing resistance to us and running a high temperature in the process! Why does the terminology of modern medicine draw so heavily from the dictionaries of war- with the use of terms such as 'magic bullets', 'invasion', 'elimination' or for that matter 'resistance'? How does this mentality of the 'battle field'- with its core values of aggression and fear- affect the very questions of medical research leave alone the solutions that are sought for them? It is an approach to which 'resistance' can be the only logical outcome. Given the fact that microbes are so clever and successfully resist the best of our efforts to eliminate them – is it possible we can actually learn something from them? And can we imagine a future situation where we can coexist with microbes without constantly trying to kill them or provoke them into killing us?

Dr. Satya Sivaraman- satyasagar@gmail.com

• Blog - Indian Initiative for Management of Antibiotic Resistance IIAMR

Resistance to antibiotics is becoming a worldwide problem. To tackle this problem in India, the "Indian Initiative for Management of Antibiotic Resistance -(IIMAR)" was formed. All concerned are requested to join the initiative by sending email to antibio.resistance@gmail.com. Articles, links etc. are welcome at email address. As India is a continental country, to make quick contact possible between all concerned and for quick information dissemination to all concerned, the IIMAR has created a web presence at http://save-antibiotics.blogspot.com/ which is the main website. To facilitate further web activity IIMAR has associate sites http://wewantantibiotics.blogspot.com and http//antibioresistance .blogspot.com. Visit to anyone of them can lead a visitor to all the sites through urls. The sites are active and are updated routinely. The sites have a forum for discussion, give interesting news and videos, lead to useful literature and inform about current activities in India in the related field. The sites are for everybody to use. All are invited to participate . Due credit will be given to all those who contribute. Coordinators: Dr. A. J. Tamhankar, Dr. Mira Shiva and Dr. Sujith J. Chandy