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Antibiotic Overuse and Resulting Drug Resistance

 PUBH6005 and Title Epidemiology

This assessment addresses the following learning outcomes: 

1. Apply common epidemiological concepts including incidence and prevalence of disease, mortality and survival and age standardisation 2. Recognise the role of exposure to biological, behavioural, social and environmental risks in disease patterns 3. Differentiate between different types of research designs, including observation and experimental and mixed methods designs 4. Assess levels of evidence and make recommendations 5. Interpret data arising from surveillance and research studies, including rates and ratios 6. Understand the difference between association and causation, statistical and public health significance 7. Analyse the role of epidemiology in screening and prevention programs, and assess the sensitivity and specificity of programs 8. Critically evaluate epidemiological studies, including potential for bias, confounding and chance errors 9. Identify key health indicators and sources of data

Instructions: 

Thousands of health and medical research studies are published each year, often reporting conflicting conclusions for the same issue. Therefore, a critical appraisal of studies to determine the strengths and weaknesses of research articles is the cornerstone of evidence based policy development, program development and implementation, hospital and primary care, health promotion and chronic disease management. This module builds on the last one where we learned to evaluate the validity of observed associations.

We saw in module 2 how well designed research studies emanate from a research hypothesis or a research question. In this module, students will learn to identify the objective of a published study, judge its appropriateness and determine the suitability of the study design against the stated objective(s). Students will also learn to critically appraise data collection procedures, identify possible sources of bias and the adequacy of the analysis, as well as the quality of reporting and interpretation of the findings. Whether the study addresses ethical issues such as conflicts of interest will also be considered.

A number of frameworks have been developed to assist in the critical appraisal of published research articles. Students in this module will be introduced to some of the more commonly used frameworks, such as the Critical Appraisal Skills Program Checklists. In module 3 we learned how different study designs provide different levels of reliability to support their findings depending on the objective of the study. This has been codified into what is termed a ‘hierarchy of evidence’ – from the strongest (based on the synthesis of many studies) to the weakest (simple descriptive studies). Students will be introduced to the two hierarchies of evidence that are accepted by the Australian Government’s National Health and Medical Research Council (NHMRC) (GRADE Working Group 2004, Hillier et al. 2011). Students will have the opportunity to practice their appraisal skills in the final assignment which is due at the end of Module 6.

To prepare for this assignment First consider this article on antimicrobial resistance. http://www.bbc.co.uk/guides/z8kccdm Antimicrobial resistance is an emerging global public health problem that has been linked to the use of antibiotics by the livestock industry, doctors over prescribing antibiotics and people not taking a full course of antibiotics. 

 Construct a research question that seeks to address a specific aspect of the issue of antimicrobial resistant bacteria. 

 Select 5 studies relevant to your research question about antimicrobial resistant bacteria (a mixture of observational and RCTs, supporting and not supporting the hypothesis). 

 Rank the studies according to the FORM (Hillier et al., 2011) or GRADE levels of evidence (The GRADE Working Group, 2008). 

 Review the frameworks in the Learning Resources (Bonita et al., 2006, Rychetnick et al.,2006, Young & Solomon, 2009 and the critical appraisal skills program (CASP) checklist). Write a 2,500-word paper that includes:

  • An introduction - introduces the topic, outlines background information to your research question and finishing with the research question. This sets the context for the rest of the assignment. 
  • Methods - explain how you found the five articles that you critically reviewed, including the databases you used and the search strategy/keywords you searched with. Also mention which checklist/method you used to critically appraise the articles. 
  • NOTE: be consistent and use the same source for all of your studies - suppose you had an RCT, a case-control study, a cohort study and a cross sectional study, you need to use checklists from the same source (for example, each of the different CASP checklists). This ensures that your approach to reviewing the articles is consistent across the different study types. Results – first rank the studies using either the FORM (Hillier et al 2011) or GRADE levels of evidence (The GRADE Working Group, 2008), then critically appraise the studies using one of the frameworks outlined in the Learning Resources (Bonita et al. 2006, Rychetnick et al. 2002, Young and Solomon, 2009 or the CASP checklists). You can put this information in a table. Include an assessment of the suitability of the study design to answer the research question, analysis of the potential for bias, confounding and chance errors, and an evaluation of ethical considerations, but stick to factual statements here – interpretation of the findings should be written in the: 
  • Discussion - outline your interpretation of the findings, conclude which is (are) the highest quality study(ies) and why, discuss the potential for study findings to be implemented in policy and practice, and make recommendations to address any gaps in the literature. Also include a discussion of limitations near the end of that section.; 
  • Conclusion – one concluding paragraph summarising the key points from the paper.


Answer

Introduction

 Financial costs associated with health are increasing significantly due to uncontrolled and overuse of antibiotic without any benefit in therapeutic use. Literature studies have revealed the various negative health consequences associated with overuse of antibiotics. These include overall reduction in the micro-biota, increased risk of infections, immune-compromised state and inflammatory bowel diseases. Moreover, it not only leads to various health problems, but also, it causes antibiotic resistance. More importantly, it has been a major public health problem and the most important factor in the emergence of antibiotic resistance cases globally. This trend is more prevalent in pediatric patients. Almost fifty percent of the antibiotic prescriptions in children were found to be unnecessary. The diseases that can be treated with antibiotics are being prescribed various broad spectrum antibiotics overuse such as overuse of amoxicillin and clavulanate combination, second- and third-generation macrolides antibiotics, quinolones or cephalosporins (Crump et al., 2015). This essay is aimed at determining the research that has been done in relation to antibiotic overuse and the resulting drug resistance. It will begin by determining the search strategy, results and then comparing five published articles that are related to the research on antibiotic resistance using CASP tool and FORM ranking. Secondly, there will be a discussion regarding the important findings of the five articles, followed by drawing a final conclusion.

Methods 

The research for the relevant literature articles was done in two steps. Firstly, a broad search was done on Google scholar with the key terms “antibiotic resistance and antibiotic overuse”. After this the search results were obtained. Again a filter with a customized search result from year 2014 was applied. 

Secondly an extensive search was done using Cinhal database. The key words that were used included “antibiotic overuse” AND “antibiotic resistance”. Filter that was applied included “English article” and articles published since the year 2014. 63 results were found. Out of these articles, the best five studies depicting the answer to the research question were chosen which critically reviewed using CASP tool. Also, FORM tool was used for National Health and Medical Research Council body of evidence matrix for analyzing the group level of evidence (NHMRC, 2009).

Results 

Five articles from the literature focused on the research question were selected. The analysis of all five articles is represented with the help of CASP table provided below. Nine questions answered "Yes", "No" or "Probable" and 2 "Open queries" were addressed in combination with a positive or negative articulation. Table 2 shows the body FORM ranking table for the body of evidence and the consequences of the investigation. The results will be translated into the discussion segment.

Table 1. Critical appraisal using CASP checklist for randomized controlled trials

                                                                                                                                   Studies

Questions
QQ
(Vaz et al., 2014)(Mangione-Smith et al., 2015)(Shin et al., 2015)(Olesen et al., 2018)(Awad & Aboud, 2015)
  1. Did the trial address a clearly focused issue?

YESYESYESYESYES
  1. Was the assignment of patients to treatments randomized?

NoYesYesYesYes
  1. Were all of the patients who entered the trial properly accounted for at its conclusion?

NoYesYesNoYes
  1. Were patients, health workers and study personnel ‘blind’ to treatment?

NoNoNoNoNo
  1. Were the groups similar at the start of the trial?

YesYesYesYesYes
  1. Aside from the experimental intervention, were the groups treated equally?

YesYesYesYesYes
  1. How large was the treatment effect?

Significant

Not
significant
Significant

Significant

Significant

  1. How precise was the estimate of the treatment effect?

PrecisePreciseNot PrecisePrecisePrecise
  1. Can the results be applied in your context? (or to the local population?)

NoNoNoYesNo
  1. Were all clinically important outcomes considered?

NoNoNoYesNo
  1. Are the benefits worth the harms and costs?

NoNoYesYesYes






Source:Table 2. NHMRC Body of evidence matrix

                                                                               Studies

ComponentsA ExcellentB GoodC Satisfactory D Poor
Evidence Base

several level
II studies
with a low
risk of bias
an
SR/several
level III
studies with
a low risk of bias
level
I or II studies
with a
moderate
risk of bias
level 1 to II
studies/SRs
with a high
risk of bias
Consistency

All studies
consistent
Most studies
consistent
Some
inconsistency
Evidence is
inconsistent
Clinical Impact

Very largeSubstantialModerateSlight
Generalizability

Populations studied are similar to target populationPopulations studied are similar to target populationPopulations studied differ to target populationPopulations studied differ to target population
Applicability
Directly
applicable
applicableProbably applicableNot applicable





Source:


FORM ranking for the body of evidence: grade C (Body of evidence provides some support for recommendations but care should be taken in its application.) 

Discussion 

• CASP Interpretation 

Randomized controlled studies provide the best evidence for this kind of research questions. This is the best level of confirmation for experimental studies; in this sense, as the research question was identified by determining the relation of overuse of antibiotics with increasing antibiotic resistance, the choice of only randomized controlled pre-screening studies seemed more satisfactory in order to be able to make a basic assessment (Awad & Aboud, 2015). The translation of the CASP tool into the selected surveys demonstrates several similarities among them, for example, the way in which they all aspired to an undisputedly committed issue with an extremely prominent purpose; each of the groups (control and intercession) were comparative to the beginning of all studies, and received such attitude that is likely to reduce the predisposition or bias; and on the grounds that most interventions are designed to be of low cost, the advantages of the test, exceeded the costs associated with the study. In any case, critical contrasts have been found and they are probably talking about a proposal to use this kind of evidence in general to make strategies and practices (Crump et al., 2015).

Randomized selection is a great tool for reducing the chances of bias so that treatment groups are identical; as far as known and unclear confounding factors are concerned. However randomization itself is not a guarantee of fair results if the investigative convention is imperfect. In Shin et al. (2014), there was no randomization, which, when identified by advocacy, could cause a shift in transmission and receptivity in collections. In such a report, in terms of accountability, not all participants who were involved in the examination were used to make a decision because of detailed prohibitions and limited assets (Shin et al., 2015).The group to which an individual is allocated can be another potential bias. It can be solved by "blinding" the subjects or potential members, which happened in the majority of the chosen studies. Because of the idea of mediation, it is possible to blind and exclude its effect on translating the results. Despite the fact that all exams are controlled ex ante and all randomized, although they pose a direct risk of predisposition. The implications of the intercessions were regarded as critical to the general opinion. Awad & Aboud (2015) defined that public educational campaigns are effective in reducing the overuse of antibiotics. Public education can help to rationalize antibiotic use, and compensate for knowledge and attitude gaps prevalent in health care setup globally. The study revealed that over more than twenty percent of the patients used antibiotic without any prescription for treatment of common cold, sore throat and cough. The study also revealed that physicians often prescribe the antibiotics to meet the patient’s expectations and only one fifty percent physicians took time to consider the careful use of antibiotics (Crump et al., 2015).

 In primary care in the United States, Olesen et al. (2018) shows that the overall antibiotic prescription in elderly patients is increasing steadily. This was shown with the help of data obtained from the rate of antibiotic prescription claim and rate of inappropriate and appropriate antibiotic prescription in United States Medicare administrative claims in older adults (aged 65 and above). While the use of certain broad spectrum antibiotics was found to decline, but certain broad spectrum antibiotics such as levofloxacin use was found to increase in relation to respiratory diagnostic categories. Also, in an investigation conducted in Seattle, Washington, Smith et al. (2015), it was concluded that the combined use of positive and negative treatment is found to be effective in reducing the risk of acute respiratory tract infections especially in children. Also, it defines that how effective communication based interventions can help in reducing the trend of unnecessary antibiotic prescription in children.

Moreover, in another study conducted in the Korea, Shin et al. (2015) variations by physician’s specialty were found. However, the chief finding was similar that concluded the uncontrolled and overuse of antibiotics in pediatric patients in relation to upper respiratory tract infections increases drug resistance cases (Smith et al., 2015).

Olesen et al. (2018) also assessed the viability of antibiotic prescription in the reduction of antimicrobial drugs resistance in elderly population. In US, high overall antibiotic use and potentially inappropriate use was observed in Medicare beneficiaries aged sixty five years old and older. The results show a drop in the antibiotic claims fell from 1364.7 to 1309.3 claims per thousand beneficiaries per year in 2011-14 (Olesen et al., 2018). It also stated that there was a potentially drop in inappropriate antibiotic claims and heterogeneous changes in individual antibiotic use was observed. Vaz et al. (2014) concluded that huge reduction in antibiotic prescription rates were observed in the early twenties. This trend has steadily increased in some age groups and that continued improvement in the use of broad-spectrum agents was possible. Despite the fact that the results are promising in these two, it is difficult to apply these results to the Australian population, given the social mistakes and levels of public educational campaigns found in developing nations in contrast to Australia (Holmes et al., 2016). Additionally, sporadic drug supply and access to medication are usually part of the creation of antibiotic resistance that can even add to financial distress in health care sector especially in developing countries.

• FORM interpretation 

  1. Level of evidence 

As per NHMRC grading, all the randomized trials are classified as second grade (Level 2). In any case, as stated above, all investigations call for a direct risk of bias, which at this point puts the confirmatory base in a satisfactory (C) classification.

  1. Compatibility

As the results of the studies are more or less same as they are pointing towards changing the practice of antibiotic overuse, but none is pointing towards its effect on antimicrobial resistance. Thus, compatibility is graded as grade C or Satisfactory (Bonita, Beaglehole & Kjellstrom, 2006).

3. Clinical effect:

The way AMR is not evaluated at any time reduces the clinical effect on the direct, which is further review. The credibility of the confirmation of the clinical trial and its clinical impact are still uncertain, as well as the term intercession / treatment (Awad & Aboud, 2015).

4. Summary of relevance and relevance:

Gathering confirmation has been made in multiple settings and population. Although most of them were carried out in the main concern, several investigations focused on the means of protection of various antibiotic drugs, distinctive conditions and different nations of focus on the Australian population. Each of these distinctions makes applicability controversial, as each nation has its own prosperous frameworks and directions, its own source of assets and obstacles to accessing it, eventually its own way of life, prospects and the impression of prosperity and illness. Nevertheless, two exams - including one in US - are performed in developed countries that make it one way or another to reasonably apply to focus groups (Unemo & Shafer, 2014).

• Consequences, suggestions and obstacles.

The consequences of the C-level review of approaches and practices are not enormous. It is suggested by the NCIPA that this level of proof should be carefully taken into account when comparing the studies, so it is proposed to perform more experimental and methodological - uniquely accurate audits and meta-research, using general articles on predisposition - the conclusions can be influenced by the clinical instructive intercession to significantly affect AMR, expanding its clinical effect (Wintersdorff et al., 2016). Further research has yet to be completed in the Australian population, so expanding levels of materiality and generality can occur in combination with a decrease in the slope. The limitations of this basic exam are mainly dialects, as only articles distributed in English are selected; as there was a point of arrest of five investigations that could be involved without mentioning a vast array of evidence; and the time, which does not change the progress in therapeutic and mechanical areas (Costelloe et al., 2010). This can lead to biased results as only the articles that were published in English language were used for answering the research question.

Conclusion

This critical assessment found that the excessive use pattern of antibiotics is responsible for drug resistance cases that subsequently affect AMR, is not unquestionable.  FORM grading revealed a C score, due to which this the results of this study cannot be used for changing the practices being followed. Nevertheless, in order to support the conclusion, the CASP program was used in each individual review, which showed several sources of bias and corresponds to the review of the NHMRC. Proposals for further investigations were considered and, in addition, the strategy's limitations were also reviewed.

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