Environmental Factors Influencing The Development And Spread Of Antibiotic Resistance

Project and Seminar Material for Public Health

Abstract

This study investigates environmental factors influencing the development and spread of antibiotic resistance. The rise of antibiotic resistant bacteria is a major challenge to global public health. The environment has a significant impact on health and infectious diseases; however, there is a lacuna of information on the relationship between the environment and antibiotic resistance. Aim: The overall aim of this thesis was to explore the relationship between antibiotic resistance and environmental components. Studies were conducted to investigate the antibiotic resistance pattern of Escherichia coli isolated from samples of children’s stool, cow-dung and drinking water from two geographical regions: non-coastal (230 households) and coastal (187 households). Findings: Participants perceived a relationship between environmental factors, infectious diseases and antibiotic use and resistance. It was perceived that behavioural and social environmental factors, i.e. patients’ non-compliance with antibiotic use, irrational prescription by informal as well as trained healthcare providers and overthe-counter availability of antibiotics are the major contributors for antibiotic resistance development. It was also perceived that natural and physical environmental factors are associated with the occurrence and prevalence of infectious diseases and antibiotic resistance. When quantitative studies were conducted, it was found that the overall prevalence of antibiotic resistance in E. coli isolated from children’s stool, cow-dung and drinking water was higher in the non-coastal than the coastal environment. Although behavioural and social environmental factors are major contributors to resistance development; natural and physical environmental factors also influence antibiotic resistance development. There was geographical variation in antibiotic resistance. It was also evident that climatic factors have influence on skin and soft-tissue infections and resistant bacteria. There is a need for further research on the influence of natural and physical factors on antibiotic resistance development and for education, information dissemination and proper implementation and enforcement of legislation at all levels of the drug delivery and disposal system in order to improve antibiotic use and minimise resistance development.

Table of Content

Title Page
Certification
Dedication
Acknowledgement
Table of Content
List of Tables
Abstract

Chapter One:

Introduction

1.1 Background of the Study
1.2 Statement of the Problem
1.3 Objective of the Study
1.4 Research Questions
1.5 Significance of the Study
1.6 Scope of the Study
1.7 Limitation of the Study
1.8 Definition of Terms
1.9 Organization of the Study

Chapter Two:

Review of Literature

2.1 Conceptual Framework
2.2 Theoretical Framework
2.3 Empirical Review

Chapter Three:

Research Methodology

3.1 Research Design
3.2 Population of the Study
3.3 Sample Size Determination
3.4 Sample Size Selection Technique and Procedure
3.5 Research Instrument and Administration
3.6 Method of Data Collection
3.7 Method of Data Analysis
3.8 Validity of the Study
3.9 Reliability of the Study
3.10 Ethical Consideration

Chapter Four:

Data Presentation and Analysis

4.1 Data Presentation
4.2 Analysis of Data
4.3 Answering Research Questions
4.4 Discussion of Findings

Chapter Five:

Summary, Conclusion and Recommendation

5.1 Summary
5.2 Conclusion
5.3 Recommendation
References
APPENDIX
QUESTIONNAIRE

Chapter One

Introduction

1.1 Background of the Study

Antibiotic resistance accounts for hundreds of thousands of deaths annually (Review on Antimicrobial Resistance 2014), and its projected increase has made the WHO recognize it as a major global health threat (WHO 2014). Conventionally, the struggle against antibiotic resistance development has mainly taken place in clinical, community, and in more recent years also agricultural settings—aiming to reduce transmission and prevent selection of resistant bacteria during antibiotic treatment. Over the past years, the role of the environment as an important source and dissemination route of resistance has been increasingly recognized (Martinez 2008; Wright 2010; Ashbolt et al. 2013; Finley et al. 2013; Pruden et al. 2013; Bengtsson-Palme et al. 2014b; Bondarczuk, Markowicz and Piotrowska-Seget 2015), butour understanding of its contribution is still limited. The lack of knowledge of how, and under which circumstances, the environment facilitates resistance development makes mitigation of the emergence and dissemination of mobile resistance factors problematic (Berendonk et al. 2015). Several authors have highlighted the need to take on a holistic perspective on antibiotic resistance, including humans, animals and the external environment—a so-called one-health approach (Collignon 2013, 2015; So et al. 2015). Increased knowledge of the environmental factors that drive resistance may ultimately allow us to build models for how resistance emerges and is disseminated (Hiltunen, Virta and Laine 2017). Although such models would be descriptive at first, as most of their parameters remain unknown, and thus lack predictive power, they still would have value as indicators of the most urgent knowledge gaps to fill in order to develop mitigation strategies.
This paper aims to conceptualize and define the factors that influence the emergence, mobilization, dissemination and maintenance of antibiotic resistance genes in the environment. We have tried to accommodate both ecological and evolutionary aspects, but without any attempt to fully cover the growing literature on the environmental dimensions of antibiotic resistance (Fig. 1). In order to define those factors, we must first spell out some basic definitions for which ambiguous meanings exist in the literature. In this paper, we follow the operational definition of resistance by Martinez, Coque and Baquero (2015), which postulates that a strain is resistant against an antibiotic if its minimal inhibitory concentration (MIC) is higher than for the corresponding parental wild-type strain.

Accordingly, we define a gene as a ‘resistance gene’ (or ‘resistance factor’) when its presence allows a bacterium to withstand a higher antibiotic concentration or when its absence increases susceptibility of the antibiotic (Martinez, Baquero and Andersson 2007), a definition that also includes many non-mobile chromosomal resistance genes. We furthermore define ‘novel’ (or ‘new’) resistance genes as genes that have not previously been described to have a resistance function, regardless of if they appear in pathogens or not, and regardless of if they appear on the bacterialchromosome or on a mobile genetic element. It is complicated to define ecological emergence (de Haan 2006), and depending on the viewpoint several definitions of when resistance genes emerge are possible (Baquero et al. 2015). In this paper, we will consider the ‘emergence’ of a resistance determinant as the event where it first appears in a context where it provides operational resistance.

1.2 Statement of the Problem

The rise of antibiotic resistant bacteria is a major global public health problem (Wales & Davies, 2015). Infections from resistant bacteria are becoming increasingly difficult and expensive to treat. The environment has a significant impact on human health. It also plays a key role in the distribution and prevalence of infectious diseases. There is a multi-faceted inter-relationship between the environment, health, infectious diseases, antibiotic use and resistance. However, there is a gap in information regarding the relationship between antibiotic resistance and environmental components. In community environmental health research, qualitative methods are essential for understanding community perceptions of specific or unknown issues (Wales &Davies, 2015).. Therefore, this study was undertaken among communities to find out their perceptions regarding the relationship between antibiotic resistance and environmental components, which were then further explored quantitatively

1.3 Objective of the Study

The main objective of this study is to investigate environmental factors influencing the development and spread of antibiotic resistance.

Specific objectives include to:

Evaluate the Characteristics of the households from the non-coastal and coastal environment.
Examine the Antibiotic resistance patterns of E. coli in non-coastal and coastal regions.
Investigate the impact of Antibiotic resistance patterns of E. coli on non-coastal and coastal regions.

1.4 Research Questions

What are the Characteristics of the households from the non-coastal and coastal environments?
What are the Antibiotic resistance patterns of E. coli in non-coastal and coastal regions?
What is theimpact of Antibiotic resistance patterns of E. coli on non-coastal and coastal regions?

1.6 Significance of the Study

This study is santibiotic-resistantneral public. Its findings and recommendations will help significantly the proper application anti-biotics in combating infectious diseases. The findings and recommendations along side the reviewed literatures in this study will add significantly to the previous knowledge of students and scholars in the medical profession. The recommendations of this study will serve as a guideline for stakeholders in the health sector.

1.7 Scope of the Study

This study investigated environmental factors influencing the development and spread of antibiotic resistance. The study also encompasses theimpact of Antibiotic resistance patterns of E. coli on non-coastal and coastal regions, the Antibiotic resistance patterns of E. coli in non-coastal and coastal regions and the Characteristics of the households from the non-coastal and coastal environments.

1.8 Limitation of the Study

Simon (2011) defines limitations as the weaknesses in the study that are beyond the control of the researcher and delimitations “are those characteristics that limit the scope and define the boundaries of your study” but can be controlled by the researcher. The study also focused only on grade 10 and 11 learners because in these grades the learners should be preparing themselves for the matriculation exit qualification. This study was constrained by some factors. Firstly, the time frame allocated for the completion of this study was not enough for the researcher to extensively carry out research based on the theme of this research work. On the other hand, the research participants were not willing to participate in responding to the administered questionnaire of this study. Also, the required materials like journals and articles needed for the proper completion of this study were not readily available online and offline. All these constraint put together, ultimately determined the extent to which the researcher was able to go in this study.

1.9 Definition of Terms

Antibiotic Resistance:

Antibiotic resistance is the ability of certain strains of bacteria to develop a tolerance to specific antibiotics to which they once were susceptible.

Climate Change:

Climate change refers to a statistically significant variation in either the mean state of the climate or in its variability, persisting for an extended period (operates over decades or longer).

Climate Variability:

Climate variability refers to variations in the mean state and other statistics (such as standard deviations, the occurrence of extremes, etc.) of the climate on all temporal and spatial scales beyond that of individual weather events (short-term fluctuations around the average weather). Coastal region: Ten kilometres of the landside of coastal structures.

Healthcare Professionals:

The health care professionals are educated, trained, certified, or licensed to provide healthcare.

Highest Temperature:

The highest maximum air temperature observed at the site, calculated over all years on record.

Household or Family:

A group of persons who commonly live together and would take their meals from a common kitchen unless the exigencies of work prevented any of them from doing so.

Lowest Temperature:

The lowest recorded temperature observed at the site, calculated over all years on record. Relative humidity: The ratio of the actual vapour pressure to the saturation vapour pressure expressed as a percentage.

Time-series:

An ordered sequence of values of a variable at equally spaced time intervals. Trend: A trend is a long-term movement in a time-series without calendar-related and irregular effects.

1.10 Organisations of the Study

This research work is categorized in five chapters, for easy understanding, as follows.

Chapter one is concern with the introduction, which consist of the (overview, of the study), background to the study, statement of problem, objectives of the study, research questions, significance of the study, scope and limitation of the study, definition of terms.
Chapter two encompasses the conceptual review theoretical review and empirical reviews on which the study is based.
Chapter three deals on the research design and methodology adopted in the study.
Chapter four concentrate on the data collection and analysis and presentation of finding.
Chapter five gives summary, conclusion, and recommendations made of the study.

Chapter Five

Summary, Conclusion and Recommendation

5.1 Summary

The community members and healthcare professionals perceived an inter-relationship between environmental factors, infectious diseases and medicines, particularly in relation to antibiotic use and antibiotic resistance. According to them, although behavioural and social environmental factors are the major contributors to antibiotic resistance, natural and physical environmental factors are also associated with occurrence and prevalence of infectious diseases and antibiotic resistance (Papers I & II). Quantitative studies supported the perceptions of the participants involved in the qualitative studies. It was observed that antibiotic resistance pattern varied geographically; the overall prevalence of antibiotic resistance in E. coli isolated from children’s stool, cow-dung and drinking water was higher in the non-coastal than the coastal environment (Paper III). Furthermore, seasonality in the incidence of SSTIs and MRSA was observed (Paper IV). Time series analysis of data collected in this context over 18 months revealed that average weekly maximum temperature above 33°C and minimum temperature above 24°C coinciding with relative humidity between 55% to 78% is a favourable combination for the occurrence of SSTIs, SASSTIs and MRSA infections; this combination of temperature and relative humidity is observed in Odisha during late summer (mid-April to mid-June), when peak incidence of SSTIs, SA-SSTIs and MRSA infections occurred during the study period (Paper IV).

The views put forward by the participants suggest that behavioural and social environmental factors are the major contributors for the development of antibiotic resistance. There is variation in community members’ knowledge of infectious diseases, antibiotic use and resistance. The major behavioural and social factors affecting antibiotic resistance seen were, behaviour of patients and professionals, as well as policy and regulatory issues. The participants suggested that antibiotic resistance can be prevented by reducing the need for antibiotic use.

Community members’ knowledge of infectious diseases and antibiotics varied according to their education and social environment i.e. urbanisation of the community. The literate and urban members were more aware of infectious diseases and they had heard the term antibiotics. The participants were confident in the effectiveness and safety of antibiotic, but unfamiliar with their disadvantages and side effects. They believed that antibiotics were ‘quick’, ‘effective’, ‘strong’, ‘safe’ and a ‘life saver’ medicine, similar to the findings of a previous study on community perceptions in the United Kingdom . However, in the present study (Paper I) participants were aware of side effects of antibiotics. The participants perceived that antibiotics were useful for the common cold, which indicates poor knowledge of the appropriate use of antibiotics, similar to other findings. The community members didnot understand the term antibiotic resistance and how resistance develops. However, they were aware of non-functioning of some medicines including antibiotics, for example penicillin. A previous study from India showed that community members perceived that if the same medicine is used repeatedly it might become ineffective after some time . The participants in this study also viewed that use of antibiotics in farm animals may influence antibiotic resistance in humans [134]. According to Hawkings et al., community members do not see bacterial resistance as a personal threat but something that occurs in hospitals [135]. Some community members (Paper I) also thought that excessive use of chemicals in cultivation and climate variability might be contributing factors to non-functioning of medicines.

Three major health system and policy factors were seen as influencing antibiotic use and resistance development. These factors were patients, the health system and prescribers, and policy and regulatory issues. The participants viewed that noncompliance with medicine use, irrational prescription by trained prescribers and informal healthcare providers (quacks), as well as availability of fake and low quality medicines, and over-the-counter antibiotics, are all contributors to antibiotic resistance development. According to Heymann, behaviours such as excessive demand for antibiotics by the community and over- and under-prescription of antibiotics have a “remarkable impact” on selection and survival of resistant bacteria [11]. Siddiqi et al. from Pakistan – a neighbouring country with a similar situation – suggest that a combination of non-regulatory (by providing training and information) and regulatory (by implementation of policy) interventions, directed at healthcare providers and community members would be helpful for rational prescription of medicines [136].

5.2 Conclusion

Community members as well as health care providers perceived an interrelationship between environmental factors, infectious diseases, and antibiotics use and resistance. Community members’ knowledge and perceptions varied according to their social environment and individual education.Behavioural and social environmental factors like patients’ non-compliance with antibiotic use, irrational prescription by informal as well as trained healthcare providers and over-the-counter availability of antibiotics were seen as the major contributors to resistance development.

There is lack of information and awareness about prudent use of antibiotics. There is a need for information, education, dissemination and proper implementation and enforcement of legislation at all levels of the drug delivery and disposal system in order to improve antibiotic use and to prevent pharmaceutical contamination of the environment.The prevalence of antibiotic resistance in E. coli isolated from both community and environmental sources was higher in the non-coastal than the coastal environment.Climatic factors have influence on skin and soft-tissue infections and resistant bacteria, i.e. methicillin-resistant S aureus.

5.3 Recommendation

The community members mentioned the need for the proper use of antibiotics. They also admitted their lack of knowledge about prudent use of antibiotics. This suggests the need for the development of a strategy or action plan for creating awareness about prudent use of antibiotics. There is also a need for education and awareness campaigns among community members on hygiene practices and other measures to minimise spread of infections and thus unnecessary use of antibiotics.

The healthcare professionals admitted that knowingly or unknowingly they do not prescribe antibiotics rationally either due to demand from patient or as they suspect infection. This suggests that the awareness about antibiotic resistance among healthcare professional is essential. Present results also recommend that a policy is needed to update the knowledge of registered medical practitioners regarding antibiotic use and resistance at regular intervals. There is also a need for availability of laboratories for susceptibility testing in rural settings.

The participants in this study informed that unauthorised practitioners such as ‘quacks’ serve patients in remote areas, indicating a lack of well-educated trained healthcare staff in remote areas. Therefore, there is a need to provide supportive training and orientation for ‘quacks’ on appropriate treatment, since they are the only people providing health services in remote areas where there is lack of trained healthcare providers. However, there is also need for laws to restrict ‘quacks’ to only carry out primary treatment or first aid, followed by referral to local trained prescribers.

The findings showed a difference in antibiotic resistance in bacteria from water, stool and cow-dung collected from two different geographical regions; coastal and non-coastal. Further research is needed to find out the reasons for geographical variation in antibiotic resistance to know the actual factors responsible for antibiotic resistance and actions to eliminate those factors.

It was also observed from the climatic records of Bhubaneswar meteorological centre that, over the decades, there is a trend for increase in ambient air temperature, which the participants in qualitative studies perceived as cause of health consequences and infectious diseases. As a significant association between climatic factors and skin and soft-tissue infections was observed, it may be proposed that studies may be undertaken to explore the relationship between other infectious diseases and climatic factors.

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