Antibiotic use, environment and antibiotic resistance

30 Pages·2008·0.24 MB·English

Antibiotic use, environment and antibiotic resistance:
A qualitative study among human and veterinary
health care professionals in Orissa, India
.

Krushna Chandra Sahoo

Supervisors:
Cecilia Stålsby Lundborg
Associate professor, Division of International Health, IHCAR, Karolinska Institutet
Professor, Nordic School of Public Health
VISITING PROFESSOR, R.D. Gardi Medical College, Ujjain, India

Ashok. J. Tamhankar
PROFESSOR EMERITUS, N.G. Acharya and D.K. Marathe College, Mumbai, India
VISITING RESEARCHER, Karolinska Institutet, Sweden
VISITING PROFESSOR, R.D. Gardi Medical College, Ujjain, India
NATIONAL COORDINATOR, Indian Initiative for Management of Antibiotic Resistance
(IIMAR)
Ex-Head, PSIT, Bio Medical group, BARC, Mumbai

Masters thesis in Applied Ecology: 30ECTS
Date: 25/08/08
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Abstract
Objective: To explore views of medical doctors, veterinarians and drug sellers on use of
antibiotics on humans and nonhumans and on factors that influences the development of resistance
to antibacterial agents. Further, to look at the bi-directional relationship between antibiotic use and
environment.
Methods: The study was a qualitative explorative interview study, analysed using conventional
content analysis. It was conducted in Orissa, India. Data were collected by face to face semi
structured interview. The interviews were tape recorded and transcribed into Oriya, then translated
in to English. Each paragraph or sentence was coded. Similar codes were clustered together and
collapsed into sub categories and categories. The main themes were allowed to emerge, based on
the relationship between categories.
Findings: The main finding of the study was mishandling and abuse of antibiotics in patients as
well as at professional level due to weak implementation of legislation, which appears to be the
major cause of antibacterial agent resistance. Incomplete course or dose due to poverty in rural
area and self medication in urban area are more common. The study also showed that climatic
factors, pollution and population density are the major ecological factors which influence antibiotic
prescriptions. Another major finding of this study was that, due to improper disposal system of
pharmaceuticals; antibiotics are contaminating air, water and terrains which can cause major risk
to aquatic and grazing animals.
Conclusion: This study emphasises the need for comprehensive actions including information,
training, legislation and education at all levels of drug delivery system to rationalize antibiotic use
by improving prescribing pattern and creating awareness among consumers. Proper disposal of
pharmaceutical wastes is required to prevent the contamination of environment from
pharmaceutical pollutants. Further study is essential concerning environmental impact of
antibiotics.

Key words: Antibiotic use; antibiotic resistance; environment; qualitative; conventional; content
analysis; veterinarians; medical doctors; drug sellers; Orissa; India.

Acknowledgements
First of all, I would like to thank all the interviewees for their valuable contribution to this study.
Also I would like to express thanks to my friends Dr. Biswal and others for their cooperation and
valuable time during data collection. I would like to express my gratitude to my course coordinator
Dr Stefan Weisner and Dr Louise Silwer, Dr Eja Pedersen at Halmstad University for their
precious support. Especially, I wish to thank Dr Eva Johansson at Nordic School of Public Health
and IHCAR, Karolinska Institutet for her significant contribution during data analysis. At last I
would like to say timely guidance, support and supervision of my supervisors Dr. Cecilia Stålsby
Lundborg and Dr. Ashok. J. Tamhankar is unforgettable. The study was funded by Nordic School
of Public Health.

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Introduction

Background of the Study

Mortality as a result of infectious diseases represents one-fifth of global deaths [1]. The success of
antibiotics against diseases caused by microbes is great achievements in modern medicine. Over
the years, antibiotics have saved the lives and eased the suffering of millions of people. Currently,
pathogenic bacteria are becoming resistant to antibiotics at an alarming rate. It is frequently
recognized that the widespread misuse of antibiotics in human health, veterinary, aquaculture,
agriculture and household products, represent an important reason for the increase in antibiotic
resistance [2,3,4,5]. Due to enormous growth of global trade and travel, both infectious diseases
and resistant microorganisms spread between continents [2]. Antibiotic resistance has been called
one of the World’s most burning public health problem affecting both current and future
generations.

Antibiotic resistance is the ability of bacteria to resists the effect of an antibiotic. As per the
previous literature review study Salmonella enterica resistant to ampicilin, choramphenicol and
cotrimaxazole; Vibrio cholerae strains resistant to cotrimoxazole and tetracycline; Campylobacter
species resistant to fluoroquinolone; and Streptococcus pneumonia resistant to penicillin,
chloramphenicol, tetracycline and erythromycin; Mycobacterium tuberculosis resistant to multi-
drug therapy are reported [6].Above study indicates that antibacterial resistance is the pressing
public health problem.

The nonhuman use of antibiotics include; veterinary, agriculture, aquaculture and as growth
promoters in pig and poultry production. As per the World Health Organization (WHO) report,
various antibiotics are licensed and used in fish and shrimp production; and half of the total
amount of antibiotics produced globally is put for nonhuman use [5]. All antibiotics used in
veterinary medicine are the same or closely related to antibacterial used in human medicine and
that’s why they induce cross-resistance [7]. The widespread misuse of antibiotics in nonhumans
are creating serious problem in human health care system. Due to this reason WHO strongly
recommends that antibiotics used for treating infections in humans should not be used as growth
promoters in animals. Sweden banned the use of all animal growth promoters in 1986. In the year
1997 European Union encouraged, banning of all antimicrobial animal growth promoters which
are used in human medicine [5].

Environmental factors have significant impact on antibiotic use. Both abiotic and biotic factors
affect the human health. Due to climate change, pollution and high population density the micro-
organisms are rapidly spreading in the surroundings and are impacting human health, hence
antibiotic prescriptions. The literature review showed that there is not any scientific study on
influence of ecological factors on antibiotic prescriptions.

Around the world, thousands of tons of pharmaceuticals are used annually but little is known
about the ultimate fate and potential effect of several drugs after their intended use. Recently few
studies have demonstrated that many pharmaceuticals are incompletely eliminated at sewage
treatment plants and some antibiotics are found in municipal waste water, surface water and
agriculture waste [8,9,10,11,12]. The literature review showed that there is no published qualitative
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study on environmental impact of antibiotics. A major concern so far has been that antibiotics
found in aquatic environment may cause increased resistance among natural bacterial populations.
Antibiotics remain biologically active even at low levels, so their impact and environmental
interaction can be much subtler and complex than many contaminants. Therefore, antibiotics and
its ingredients in the aquatic environment are warning signals for current and future public health
as well as ecological problems. Qualitative study is necessary to explore the community response
and consciousness regarding environmental issue of antibiotics.

Due to resistance, scientists are trying to create new antibiotics to replace old ones. In recent
years, the pharmaceutical industry has produced few new drugs. On average, research and
development of a single new antimicrobial takes 10-20 years and costs US $ 500 million dollars to
bring into the market [13]. The rise of antibiotic resistant bacteria is a major public health crisis as
infections from resistant bacteria are becoming increasingly difficult and expensive to treat. When
bacteria become resistant to first line antibiotics, treatment has to be switched to second or third
line drugs, which are generally expensive [2]. Many of second and third line therapies for drug
resistant infections are unaffordable due to their high price. Over the last decade, almost, every
type of bacteria has become resistant and less responsive to antibiotic treatment when it is really
needed. That’s why more research and law for prudent use of antibiotic is essential.

Antibiotic resistance is a global problem. In Asia resistance problem is prominent [6] and in
India the consequences of antibacterial resistance will be severe. There is rapidly growing
pharmaceutical industry [14] and also high use of antibiotics in India. The economic capability to
use second or third line antibiotics in cases where bacteria have developed resistance to first line
treatment is lacking for ordinary people. Lack of surveillance and consequent late detection of
resistant strains can further aggravate the situation. As per my knowledge, there is a lacuna of
information regarding health care professionals’ perception on antibiotic resistance and
environmental impact of antibiotic use in Orissa, India. Due to this reasons we took a qualitative
study to explore the views of human and veterinary health prescribers along with dispensers on
antibiotic resistance; and to develop intervention for policymakers.

A qualitative research is the collection, analysis and interpretation of comprehensive narrative
data in order to gain insights into a particular phenomenon of interest. Qualitative variable is not
quantifiable. It depends upon attributes. It is useful for describing and answering questions about
participants and contexts. It explains how economic, political, social and cultural factors influence
health and society, i.e. environmental and organizational factors. While qualitative approaches
assess in discovery of categories and define interpretation of different objects, quantitative
approaches help to count and analyse them statistically [15]. Qualitative content analysis is used to
organize the results according to emerging themes. It is a research method for the subjective
interpretation of the content of the text data through the systematic classification process of coding
and identifying themes or patterns.

Literature Review

Infectious diseases have the potential, like no other group of diseases, to spread rapidly over large
distance in a short time. Due to overuse and misuse of drugs, bacterial resistance to antibiotics is
accelerating at a disturbing rate around the world. According to WHO report most of the rising
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antimicrobial resistance problem in human medicine is due to the overuse and misuse of
antimicrobials by doctors, other health personnel and patients. Education on antimicrobial
resistance and prudent antimicrobial use is lacking amongst dispensers and prescribers of
antimicrobials [5]. Previous study in India declares, rising antibiotic resistance problems, largely
due to wide spread and irrational use of antimicrobial agents in hospitals and the community in
developing countries. Antibiotic resistance increases not only the healthcare costs, but also the
severity and death rates from certain infections, that could have been avoided with prudent
antibiotic use [16]. The spread of penicillin-resistant pneumococci and multi drug resistance
tuberculosis is due to airborne transmission. Large numbers of commercial preparations, unethical
drug promotions by pharmaceutical houses and irrational prescribing habits of clinicians are the
important reasons for irrational prescription of drugs in clinical practice [17].

As per the previous study, self-medications with antimicrobials are another major factor
contributing to resistance [2]. Self-medication percentage is high in urban areas in comparison
with rural area [18]. Similar study in Europe elucidates that there are significant differences in
levels of public attitudes, beliefs and knowledge concerning antibiotic use, self medication and
antibiotic resistance. Awareness about antibiotic resistance was the lowest in countries with higher
prevalence of resistance [19]. Patients who self-medicated were more likely to use an inadequate
drug or dose [20]. A qualitative study on self-medication in Latine America points out, that
patients believes that visit to physician for a diagnosis and prescription were unnecessary when the
patient was familiar with the symptoms and it had previously responded to antibiotic treatment
[21]. In Trinidad and Tobago, inappropriate use of antimicrobials resulted from self-medication,
over the counter availability at the community pharmacy, prescribing on demands, and lack of
regulatory control [22].

Antibiotic resistance is a major public health problem in Europe and worldwide. Its spread is
partially due to inappropriate antibiotic consumption at the human and animal level and this can be
controlled through better use of these antibiotics and their harmonised surveillance [23]. In
developing countries complex socioeconomic and behavioral factors are associated with antibiotic
resistance. There is a misuse of antibiotics by health professionals, unskilled practitioners, and
laypersons; poor drug quality; unhygienic conditions accounting for spread of resistant bacteria;
and inadequate surveillance [24]. Explanations of distinction between virus and bacterium often
led to perceived confusion [25]. In both France and Britain about 90% of the patients receive
antibiotics for tonsillopharyngitis [26]. Similar study on South India showed that purulent
discharge, fever and patient satisfaction were the strong influences to prescribe an antibiotic; and
belief of prescribing a broad spectrum antibiotic [27]. According to WHO, in many countries,
including several developed countries, antimicrobials are available over-the-counter and may be
purchased without prescription [5]. Similar study in Kerala, India, explains 20% of the antibiotics
are purchased without doctor prescription, out of one thousand people four are engaged in
unsupervised self-medication using antibiotics. The most commonly used groups of drugs are
tetracycline, ampicillin, coxacillin and amoxicillin; cephalexins and ciprofloxacin taken in acute
respiratory illness [28]. Previous study in Latin America enlighten there is lack of physician
training on consumer’s education on antibiotic use and abuse and its consequences [29]. Public
knowledge regarding antibiotics is typically poor [30]. Similar study from nine African countries
suggest that, since most people purchase their drugs from unqualified drug sellers, educating these
drug sellers would probably be even more beneficial for public health in many low-income
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countries [31]. A cross sectional study in Zimbabwe shows that, there is a low sale of antibiotics
without prescription which is in sharp contrast to other studies from low income countries [32].
Non-prescribed use of antibiotics is very low in Sweden compared with other European countries
[33].

The nonhuman use of antibiotics includes therapeutic, prophylactic and growth promotion use
in food producing animals, agriculture, horticulture, aquaculture and industrial use. A recent
review in Europe has revealed that an average amount of 100milligrams of antimicrobials are used
in animals for production of one kilogram of meat for human consumption [5]. Generally the
antibiotics used in veterinary medicine are fluroquinolone, penicillin, tetracycline,
chlorotetracycline [7,34,35], cephalosporin [7,36,37], procaine penicillin dihydrostreptomycin,
trimethoprim sulphonamides [38] and virginiomycin [34]. A pervious study in the United States
showed that, a significant source of antimicrobial resistant food borne infections in humans is due
to acquisition of resistant bacteria originating from animals [39].

There is a potential environmental impact of antibiotics. Antibiotics are entering in large
quantities into the environment. According one study, the primary pathway of antibiotics into the
environment is the use and disposal of out-of-date or unwanted medicines whose ecotoxicologic
consequences with their presence are less clear [40]. As per a study in Patancheru, which is a
major production site of the generic drugs for the world market near Hyderabad in India, high
levels of several broad spectrum antibiotics specifically ciprofloxacin are present in aquatic
environment [10]. A degree of multiple antibiotic resistances was observed in seven different
Vibro species in the coastal water of Bay of Bengal at Orissa coast [41]. Antibiotics have been
detected in surface water in many countries such as Canada, Germany, United States and other
European countries [42]. A study in Australia mentions presence of three antibiotics i.e.
ciprofloxacin, norfloxacin and cephalexin both in sewage effluent and environmental waters
downstream from a sewage discharge. [11]. As per an earlier study in Germany in surface water,
out of fourteen pharmaceuticals, 30% are antibiotics [12] and the sewage water also contains
antibiotics and its degraded compounds [43]. In Spain, Enterobacteriaceae and Aeromonas spp.
fresh water bacteria are resistant to nalidixic acid, quinolones and tetracycline [44].

Purpose of the Study

To explore views of medical doctors, veterinarians and drug sellers on use of antibiotics in humans
and nonhumans and on factors that influence development of resistance to antibacterial agents.
Further, to look at the bi-directional relationship between antibiotic use and environment.

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Methods

Study design

The study was a qualitative explorative interview study, analysed using conventional content
analysis. Conventional content analysis is generally used to describe a phenomenon. Content
analysis is used to provide knowledge and understanding of phenomenon under study [47].

Study area

The study was conducted in Orissa, India (Figure 1). Orissa is located on the east cost of India.
It has a population of 32 million, which is about four percent of the population of India. About
87% of the population lives in villages, out of which 25% are tribal. It extends over an area of
155,707 square kilometers accounting for 4.9 percents of the total area of India [50].

Fig 3: Study area in Orissa, India.

Out of the 30 districts of Orissa, four districts were selected for the study (Figure 2) with the
intention of bringing in variety in sampling, based on the economy of the people and ecology of
the districts. Among these districts two were urban and two rural. The two urban districts were
Cuttack and Khurdha which are economically advanced and near to the sea -Bay of Bengal. The
geographical area of Cuttack is 3,733 square kilometers with more than 2.3 million inhabitants and
Khurdha- 2,889 square kilometers with about 1.9 million inhabitants. These districts have a high
population density and a high percentage of literacy. The two rural districts were Koraput and
Malkangiri which are economically backward and tribal dominant. These two districts are far from
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the sea with forests and hills. The geographical area of Koraput is 8,379 square kilometers with
about 1.2 million inhabitants, among them about 51% are tribal. The geographical area of
Malkangiri is 6,190 square kilometers with near about 0.5 million inhabitants. In these two districts
literacy rate is very low, about 32% in Malkangiri and 37% in Koraput and most of the people are
financially weak [50].

Participants Details

In this study three groups of health care providers were selected- medical doctors, veterinarians
and drug sellers. Amongst the 24 interviewees, eight participants from each group were included.
Among these eight interviewees four were from rural and four from urban districts. From each
district two interviewees were included for the study from each group. Among the 24 participants
only two medical doctors were female. Detail information of interviewees is summarized in
Table.1.

Table.1 - Study Area and Interviewees
Interviewees Study Area Orissa, India
Rural Districts Urban Districts
Malkangiri Koraput Cuttack Khurda
Bhubaneswar
Medical M1 M2 M3 M4 M5 M6 M7 M8
Doctors
Sex: Female Male Female Male Male Male Male Male
Age: 31 years 29 years 27 years 47 years 65 years 72 years 53 years 51 years
Qualification: MD Com. MBBS MBBS MS Surgery MD Medicine MS Surgery MS Surgery MD TB Spl.
Medicine
Experience: 6 years 3 years 2 years 21 years 41 years 40 years 28 years 28 years
Interview Place: Resident Resident Resident Resident Clinic Clinic Hospital Resident
Interview Duration
in minutes: 25 20 25 29 25 40 36 30
Veterinarians V1 V2 V3 V4 V5 V6 V7 V8
Sex: Male Male Male Male Male Male Male Male
Age: 54 years 30 years 71 years 50 years 50 years 38 years 55 years 48 years
Qualification: M.V.Sc B.V.Sc B.V.Sc M.V.Sc M.V.Sc Poultry Mg. M.V.Sc B.V. Sc
Experience: 30 years 5 years 37 years 27 years 30 years 10 years 32 years 25 years
CDVO Retired CDVO
CDVO
Interview Place: Office Hospital Resident Hospital Hospital Farm Office Hospital
Interview Duration
in minutes: 40 20 10 21 25 20 17 15
Drug Sellers D1 D2 D3 D4 D5 D6 D7 D8
Sex: Male Male Male Male Male Male Male Male
Age: 34 years 29 years 50 years 39 years 44 years 27 years 34 years 35 years
Qualification: B.Pharma B.Pharm B.Pharm B.Pharma B.Pharma B.Pharma B.Pharma B.Pharma
Experience: 10 years 4 years 34 years 12 years 17 years 5 years 10 years 10 years
Interview Place: Shop Shop Shop Shop Shop Shop Shop Shop
Interview Duration
in minutes: 12 11 20 15 12 10 15 10
M- MBBS Doctors, V- Veterinarians and D- Drug Sellers
MBBS-Bachelor in Medicine and Bachelor in Surgery, CDVO- Chief District Veterinary Officer, M.V.Sc- Master in veterinary
Surgery, B. Pharma- Bachelor in Pharmacy

Each participant was contacted by the author before the interview. Primary contact was through
telephone from Sweden 15 to 20 days before interviews. Thirty six interviewees were contacted
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among them 24 were considered for study to maintain the equality among study area and different
group of participants.

Data collection procedure

Data were collected by face to face semi structured interview. Specific Interview guides were
prepared for each group of professionals. Interviews were conducted both in local language and
English. The interviews were recorded on tape and lasted approximately 20 to 25 minutes. Out of
the eight medical doctors five interviews were held at their residence, two in clinic and one in the
hospital. In case of veterinarians four interviews were held at hospitals, two at office and one each
at residence and farm. Interviews for all the drug sellers were held at the medicine shops. All the
interviews were conducted by the author who belongs to the study area, fluent in Oriya and
English languages and having an educational background in Biological and Environmental Science
as well as has experience in social services.

Data Analysis

The tape recorded interviews were transcribed verbatim in Oriya and then translated into
English. Content analysis was applied for analysing the data. Each sentence or paragraph was
coded. The tape recorded versions, Oriya and English transcripts of data were consulted time and
again during coding procedure to avoid misinterpretations of the full meaning of the texts.

One of the most basic decisions when using content analysis is selecting the unit of analysis.
Meaning unit was selected from the interview transcript. A meaning unit is the constellation of
words or statements that relates to the same central meaning; it can be called coding unit or content
unit [48]. From the meaning unit, condensed meaning unit i.e. interpretation of the underlying
meaning or description close to the text was generated. A code i.e. label of meaning unit was
formulated from condensed meaning unit. Similar codes were clustered together and collapsed into
sub-sub categories, subcategories and categories. A category is a group of content that shares a
commonality. The main themes i.e. emergent concepts were based on the similarities between
categories.

Ethical Consideration

Before the interview, information was given about the purpose of the study to the interviewee,
the interview guide was shown and a consent form was signed by the interviewees. The
interviewee was informed that he or she can withdraw from the study at any time. All the
interviews were carried out in complete privacy and the name of interviewees are confidential.

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Results

Two major themes emerged from the analysis of the interviews.

´Antibiotic handling contributing to the development and spread of resistance` and ´Bi-
directional relationship between antibiotic use and environment`,

The findings are presented under each major theme/category/subcategory/sub-subcategory with
quotes from the respondents to illustrate the results. The results for theme-1 are presented in Table-
2 and for Theme-2 in Table-3.

Table-2: Hierarchy of codes theme 1- Antibiotic “handling” contributing to the development and spread of
resistance.

Theme1 Antibiotic “handling” contributing to the development and spread of resistance
Category “Handling” of Antibiotics Factors influencing resistance
Sub- Human use Nonhuman use Health system and Policy Resistance
category mechanism
in bacteria
Sub-sub Factors Factors Medical Non medical Patient factors Professional Weak legislation Drug
category considered in influencing uses in uses in factors and resistance
individual prescribing animals animals implementation level in
prescriptions bacteria
Codes Broad and High density Poultry use Growth Noncompliance Inadequate Fake medicine Conjugation
Narrow of patients Promoter prescription
spectrum Dairy farm Self-medication Without Drug
Prior Irrational use prescription tolerance
High and low prescriber Choice of Ignorance
dose routes in Improper Low quality Gene transfer
Variation in animals Poverty diagnosis medicine
Therapeutic cost Mutation
use More study Lack of awareness
Influence of Insufficient Drug
Prophylactic pharmacy Patient policy destroying
use company follow up
Drug
Choice of Unqualified Lack of staff impermeable
routes in medical
humans providers Erroneous Multi drug
posting resistance
“Higher” Global
antibiotics problem Lack of Cross
infrastructure resistance
Antibiotic
combination

1. Theme: Antibiotic “handling” contributing to the development and spread of resistance
Under this theme, two categories were identified (i) “Handling” of Antibiotics and (ii) Factors
influencing resistance.

1.1. “Handling” of Antibiotics
Antibiotics are used both in humans and nonhumans. Under this category there are two main
sub categories: (i) Human use and (ii) nonhuman use of antibiotics.

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