Next-Generation Sequencing Technology: Antimicrobial Resistance

Evidence-Based Practice Proposal: Next-Generation Sequencing Technology to Address Antimicrobial Resistance
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Abstract
Antimicrobial resistance constitutes one of the most significant healthcare sector challenges in the 21st century. Antimicrobial resistance undermines patient treatment outcomes of severe illnesses such as cancer, contributes to a more significant illness burden, as well as heightened mortality rates because of treatment failures. This report addresses the next-generation sequencing technology as an evidence-based practice (EBP) proposed to address antimicrobial resistance in society. The paper is organized into distinct sections, including problem statement, literature analysis, evaluation of the proposed EBP intervention and forecasted outcomes, implementation plan, and evaluation plan. It is a qualitative evidence-based research proposal centered on secondary research. Antimicrobial resistance is a severe societal problem undermining patient health outcomes and thus prompts the need for this proposal. Literature analysis revealed that next-generation sequencing could effectively address antimicrobial resistance and enhance health outcomes. The expected outcome relates to the project’s purpose since it would show whether the use of next-generation sequencing reduces antimicrobial resistance. In that vein, the outcome would confirm the efficacy of next-generation sequencing. Rodgers’ diffusion of innovation theory perfectly elaborates how implementing next-generation sequencing technology can mitigate the antimicrobial resistance menace in India and society. Formative and summative evaluation methods to assess the implementation of next-generation sequencing intervention to mitigate antimicrobial resistance. NGS contributes to clinical decision-making by offering diverse information levels that guide treatment with the proper antimicrobials.
Keywords: Next Generation Sequencing, Antimicrobial Resistance, Evidence-Based Practice.
Table of Contents TOC \o "1-3" \h \z \u Abstract PAGEREF _Toc82040814 \h 2Section A: Problem Statement PAGEREF _Toc82040815 \h 4Statement of the Problem PAGEREF _Toc82040816 \h 4Stakeholders PAGEREF _Toc82040817 \h 5Project Purpose and Objectives PAGEREF _Toc82040818 \h 5Section B: Literature Analysis PAGEREF _Toc82040819 \h 6Search Method PAGEREF _Toc82040820 \h 6Summary of all of the research studies PAGEREF _Toc82040821 \h 7Validity PAGEREF _Toc82040822 \h 9Reliability PAGEREF _Toc82040823 \h 9A concise summary PAGEREF _Toc82040824 \h 9PICOT Statement PAGEREF _Toc82040825 \h 10Section C: Proposed Intervention and Expected Outcomes PAGEREF _Toc82040826 \h 10Proposed Intervention PAGEREF _Toc82040827 \h 10Expected Outcomes PAGEREF _Toc82040828 \h 11Method to Achieve Outcomes PAGEREF _Toc82040829 \h 11Potential Barriers, Assumptions, and Limitations PAGEREF _Toc82040830 \h 12Outcome Impact PAGEREF _Toc82040831 \h 12Section D: Implementation Plan PAGEREF _Toc82040832 \h 13Part 1: Application of an Evidence-Based Practice (EBP) Model– Rogers’ Diffusion of Innovation Theory PAGEREF _Toc82040833 \h 13Part 2: The Ideal Practice Setting PAGEREF _Toc82040834 \h 15Stakeholders and Appropriate Communication Model PAGEREF _Toc82040835 \h 16A Timeline PAGEREF _Toc82040836 \h 16Financial Feasibility PAGEREF _Toc82040837 \h 16Section E: Evaluation of Process PAGEREF _Toc82040838 \h 17Proposed Evaluation Methods PAGEREF _Toc82040839 \h 17Description of Methods and Rationale PAGEREF _Toc82040840 \h 18How the Proposed Evaluation Methods Measure Project Objectives’ Attainment and Measurement of Outcomes PAGEREF _Toc82040841 \h 18Validity, Reliability, and Applicability PAGEREF _Toc82040842 \h 19Strategies During Undesirable Outcomes PAGEREF _Toc82040843 \h 20Implications for Practice and Future Research PAGEREF _Toc82040844 \h 20Conclusion PAGEREF _Toc82040845 \h 20References PAGEREF _Toc82040846 \h 21Appendix: A – Peer-Reviewed Journal Articles PAGEREF _Toc82040847 \h 24Appendix: B – Rapid Appraisals PAGEREF _Toc82040848 \h 38
Evidence-Based Practice Proposal: Next-Generation Sequencing Technology to Address Antimicrobial Resistance
Section A: Problem Statement
Statement of the Problem
As antibiotic usage increases, bacteria strains are becoming more drug-resistant. Antibiotic resistance had detrimental ramifications on the contemporary healthcare systems, which depend on research on antibiotics that effectively mitigate and treat infections linked to routine healthcare procedures (Roope et al., 2019). It is increasingly explicit that Gram-positive, as well as Gram-negative microbes, now meet the evolutionary problem of fighting antimicrobial chemotherapy (Partridge et al., 2018). In addition, antimicrobial resistance constitutes a global threat to people’s wellbeing and health outcomes. Antimicrobial resistance has undermined the available treatment options for serious illnesses such as cancer, increased the illness burden, and heightened mortality rates because of treatment failures (De-Oliveira et al., 2020). It also extracts high economic costs and morbidity annually by making bacteria strains immune to available medications. Therefore, identifying and comprehending antimicrobial resistance is crucial for a medical practice to treat severe infections and illnesses and prevent the threat of resistance spread. In that vein, next-generation technologies are scaling up capacities to identify and investigate antimicrobial resistance (Boolchandani & Dantas, 2019). Therefore, next-generation sequencing technology can be adopted to mitigate antimicrobial resistance in the community and thus improve care quality as well as patient outcomes. The goal is to enhance the mapping (understanding) of antimicrobial resistance to expand the coordination and knowledge sharing efforts, which would be significantly beneficial.
Stakeholders
The main stakeholders in the project include patients affected by antimicrobial resistance, the Indian Health Department, the World Health Organization, and healthcare professionals. The main organizational benefit derived from implementing this proposal is the potential to offer a coordinated connection between surveillance within the environment as well as within other crucial facets of the “One Health” framework (food, clinical, and food-producing animals), particularly in eliminating antibiotic resistance. The key concern in this project entails determining the optimal practice bioinformatics approach for implementing next-generation sequencing. The proposal will enhance human pathogen monitoring by encouraging collaborations that derive benefits for public health as well as outbreaks’ management (Angers et al., 2017).
Project Purpose and Objectives
The purpose of this report is to investigate next-generation sequencing technology as an evidence-based practice (EBP) proposed to address antimicrobial resistance in society. The key objectives include (a) determine whether advanced techniques of antimicrobial gene discovery, like next-generation sequencing, effectively discover antimicrobial resistance genes and (b) determine the mechanisms and drivers of antimicrobial resistance.
Section B: Literature Analysis
Search Method
The Google search engine is used to access various databases, including Google Scholar, EBSCO, and sci-hub. The databases enabled me to single out the two relevant sources to my research study on evidence-based practice, especially in healthcare. The databases were credible because they contained quality sources by credible authors; hence I chose them to make my research authentic and credible. The procedure I used for the inclusion and exclusion of sources for relevant and credible sources is the consideration of the relevance of the sources to my project proposal theme and the credibility of the authors. For instance, ‘sequencing-based methods and resources to study antimicrobial resistance’ by Boolchandani, D’Souza & Dantas is an excellent source for the project on evidence-based practices, especially in healthcare. The authors are members of the Edison family Centre for Genome Sciences and Systems Biology. The other source is the ‘Research design: Qualitative, quantitative, and mixed methods approaches’ is authored by John W. Creswell, who is a renowned author that has authored many credible journal articles on mixed research methods. For instance, he has authored 27 books and many peer-reviewed articles on mixed research methods, qualitative research, and research methods (Creswell, 2003). ‘Evidence-based practice in nursing and healthcare by Bernadette Mazurek Melnyk and Ellen Fineout-Overholt is credible because the authors are co-creators of the Advanced research and clinical practice through the close collaboration model (Melnyk & Fineout-Overholt, 2010). The model underscores the novel strategy in implementing and sustaining evidence-based practice in healthcare, which is my primary focus in the project proposal. The other consideration in my search for credible sources was the number of sources used in authoring the sources, which makes the sources a crucial appreciation of past research on the phenomenon. Some of the critical terms used include evidence, expertise, practitioner, values, and practice. The other key terms used include qualitative, quantitative, survey, design, and research. The other criteria used to select the sources is establishing the number of times they are cited by other scholars in related themes of evidence-based practice in healthcare. The other strategy for searching the sources was ascertaining whether they had employed evidence-based practice in their studies.
Summary of all of the research studies
Kwong, Firth, and Jensen’s (2018) study aimed to establish the genetic aspects related to antimicrobial resistance. Its analysis indicated that horizontal gene transfer exposes one to the acquisition of antibiotic resistance. It has high scientific merit since the results communicated what the researchers intended to measure, as evidenced in the research objective. The key strength is supporting the antimicrobial resistance subject because it highlights the genetic elements associated with the phenomenon (Kwong, Firth, & Jensen, 2018). Accordingly, Forde and colleagues (2019) sought to establish how antimicrobial resistance in ESKAPE pathogens occurs. They found that antibiotic resistance associated with ESKAPE pathogens results in severe infections and deaths. The article is relevant because it underscores the antimicrobial resistance phenomenon in ESKAPE pathogens. The objective of Boolchandani, D’Souza, and Dantas’ (2019) research was to highlight the sequence-based methods required to study antimicrobial resistance. The analysis indicated that advanced techniques of antimicrobial gene discovery, like functional metagenomics, effectively discover antimicrobial resistance genes. The findings have scientific merit since the advanced technique of antimicrobial gene discovery’s efficacy s limited to the type of antimicrobial resistance genes they can detect. The article involves the study of antimicrobial resistance; hence it is relevant to the topic (Boolchandani, D’Souza, & Dantas, 2019).
Roope and colleagues (2019) sought to establish the economic contributions to the understanding of antimicrobial resistance. Findings indicated that the cost of antimicrobial resistance is unpredictable and uncertain. Therefore, there is a need for improvement in the generation of new antibiotics. The article entails understanding antimicrobial resistance from an economic perspective; hence, it is relevant (Roope et al., 2019). In the same vein, Tacconelli (2018) conducted a study to establish the effectiveness of surveillance for controlling antimicrobial resistance. Findings noted a reduction of antimicrobial resistance requires high-quality and real-time surveillance data. There is a need to make antimicrobial resistance surveillance systems and the alignment between human and veterinary surveillance systems scientific. The research is scientifically relevant since it concerns the surveillance for controlling antimicrobial resistance (Tacconelli, 2018). Recently, Saracino and colleagues’ (2021) study aimed at establishing II and III generation sequencing of the H.pylori genome. The analysis indicated that molecular biology enhances the identification of molecular mechanisms related to the phenotypic resistance to antibiotics in H. pylori. Results noted that the next-generation sequencing method enhanced the detection of rate resistance mechanisms. The article is relevant to antimicrobial resistance because it entails the next-generation sequencing prediction of antimicrobial resistance in H. pylori.
Gunasekera and colleagues (2021) researched to establish whether DNA Prep was better than Nextra XT in Escherichia coli sequencing in a bid to reduce coverage bias. The study shows that there is no correlation between the low coverage and GC content. The article is relevant to antimicrobial resistance because it features the functioning of next-generation sequencing, which is the only remedy to antimicrobial resistance. Ribot’s (2018) study seeks to establish the efficacy of PulseNet in tracking cost-effective whole genome sequencing. Results suggested that the evolution of PulseNet will outlive the implementation of whole-genome sequencing. The article is relevant to antimicrobial resistance because it features whole-genome sequencing, which is critical in identifying the antimicrobial resistance genes (Robot, 2018). Marston and Dixon’s (2016) study aim was to establish the level of antibacterial resistance in the country. The study shows that the status of surveillance and information on antibacterial resistance is worrying given the gaps in surveillance gaps. The article is relevant to antimicrobial resistance because it involves a survey of the level of antibacterial resistance in the country (Marston & Dixon, 2016).
Holmes (2016) sought to establish the threat of stifling access to improved antimicrobials. The findings indicated that antimicrobial resistance is caused by the inappropriate use of antibiotics in all instances. The article is relevant to the current issues because it covers the drivers of antimicrobial resistance (Holmes, 2016). In addition, the Argueta (2021) study focuses on establishing the rates of antimicrobial resistance during the treatment of H.pylori in the US population. A critical analysis of the research revealed that the rate of antimicrobial resistance is increasing hence the increase in bacteria eradication failures. Findings indicated that there was efficacy in the use of next-generation sequencing to address antimicrobial resistance (Argueta, 2021). The article is relevant to the topic because it underscores the effect of antimicrobial resistance rates in treating H. pylori. Lastly, Wallace’s (2019) study seeks to establish whether antimicrobial resistance is the proximate cause of global health challenges. Results noted a correlation between the host microbiome, enteric pathogens, and antimicrobial resistance. The article is relevant to the current topic because it underscores the approaches necessary to address antimicrobial resistance in enteric diseases. (Wallace, 2019).
Validity
The research on evidence-based practice is valid because it employed credible sources as sources of information for the study. Additionally, the research is valid because the authors of the sources are credible authors with global recognition. The research’s validity is also manifest in the empirical evaluation and analysis in the study. The empirical study is a scientific study that is more reliable because project beneficiaries can statistically prove findings. The research is also valid and credible because it complied with the evidence-based practice methodology wherein a question on a problem is formulated, and a search and collating of evidence is done. The research is also valid because the participants in the research are actual participants rather than imaginary parties. This aspect makes the research credible and reliable for citation in subsequent researches on a similar topic.
Reliability
The research study is reliable because it is relevant to the project proposal theme of evidence-based practice. In this case, the adoption of evidence-based practice in healthcare and other areas fosters the scientific assessment of phenomenon, promoting quality assessments and evaluation, especially in healthcare. Then, the researcher evaluates and implements the evidence before evaluating and auditing the research findings. Finally, the dissemination of outcomes is made by publishing the research study for ease of access by any scholar researching a similar theme. The study also promotes testing variables in a natural environment; hence, the research is scientific and credible. Moreover, the research is reliable because it has provided recommendations, which recognizes the limitation of the study and offers an opportunity for further research on the subject.
A concise summary
The project proposal on evidence-based practice is supported in the research whereby the k-mers were used to establish the antimicrobial-resistant genes. In this case, the research supports the project because it employed the tenets of evidence-based practice. The research identified a problem, collected and organized evidence, and appraised the evidence before the evidence was integrated, implemented, and evaluated. The evidence is inclined towards establishing the sensitivity rate of the S. aureus genome responsible for antimicrobial resistance. The research sample of 5 k-mers was adequate for use in the study. The study adopted a qualitative approach to analyze the evidence of S. aureus as the genome responsible for antimicrobial resistance.
PICOT Statement
The evidence-based practice proposal is anchored on the PICOT Question: In a community with the prevalence of cancer patients, how effective will be the introduction of next-generation sequencing to eliminate antimicrobial resistance compared to using common antimicrobial drugs in the entire period of antimicrobial resistance? The population featured in the research study was the k-mers for predicting the microbial genes responsible for antimicrobial resistance. The researcher did the testing to establish antibiotic resistance genetic components and single-nucleotide polymorphism within S. aureus as well as M. tuberculosis, respectively. The intervention is the adoption of evidence-based practice—the adoption of next-generation sequencing to address the antimicrobial resistance menace in society. The next generation will include incorporating the k-mers in the establishment of the genes responsible for antimicrobial resistance. The method is currently the saving grace for the world, given the rampant antimicrobial resistance in many parts of the world. Regarding comparison, the evidence-based practice of next-generation sequencing in establishing the resistant genes in microbes is better than antibiotics. The antibiotics have proved unreliable because of the prevalence of antimicrobial resistance to virtually all antibiotics. Concerning the outcome, K-mers’ testing of the antimicrobial resistance genetic aspects and single-nucleotide polymorphism in S. aureus and M. tuberculosis revealed that S. aureus had a high sensitivity, hence responsible for the antibiotic resistance. The duration of the project proposal testing is the entire period that the next-generation sequencing will take. The period will be adequate to establish the efficacy of the new scientific methodology in addressing antimicrobial resistance that has rocked the global pharmaceutical fraternity.
Section C: Proposed Intervention and Expected Outcomes
Proposed Intervention
The intervention is the adoption of evidence-based practice—the adoption of next-generation sequencing to address the antimicrobial resistance menace in society. The next generation will include incorporating the k-mers in the establishment of the genes responsible for antimicrobial resistance. The method is currently the saving grace for the world, given the rampant antimicrobial resistance in many parts of the world. The intervention is appropriate and realistic for the selected practice setting. It increases microbial information availability and significantly mitigates costs, making the sequencing technology a feasible instrument for antibiotic resistance surveillance. Organizing sequencing information is a critical pre-dispensation phase prior to antibiotic resistance genetic traits evaluation. Illumina-generated brief reads could either be addressed anchored on assembly-centered techniques, where sequencing technology reads are categorized into contigs (contiguous constituents) first and then marked up in comparison to public or custom archetypical databases; or outrightly evaluated based on read-centered techniques, where resistance factors are forecasted by charting reads to a model or archetypical database directly (Boolchandani et al., 2019).
Expected Outcomes
It is expected that k-mers’ testing of the antimicrobial resistance genetic constituents and single-nucleotide polymorphism in S. aureus, as well as M. tuberculosis, would reveal that either S. aureus or M. tuberculosis has a high sensitivity responsible for the antimicrobial resistance to antibiotics. The expected outcome relates to the project objectives since it would show whether the use of next-generation sequencing reduces antimicrobial resistance (Balkhaira et al., 2019). In that vein, the outcome would confirm the efficacy of next-generation sequencing. That said, a reduction of 52% will be a manifestation of the efficacy of next-generation sequencing in fighting antimicrobial resistance. The outcomes coincide with the PICOT question. The PICOT question is: Within a community with high cancer patients’ prevalence, how practical will the introduction of next-generation sequencing be to eliminate antimicrobial resistance compared to the use of common antimicrobial drugs in the entire period of antimicrobial resistance?
Method to Achieve Outcomes
The steps of next-generation sequencing include library preparation, cluster generation, sequencing, alignment, and data analysis. The next-generation sequencing library is created at the library preparation step by fragmenting the gDNA sample and ligating particular adapters to both the fragment ends. The library is loaded into the flow cell in cluster amplification, and the fragment is crossbred to the stream cell surface. The respective destined portions are augmented into a clonal group via bridge amplification. In the sequencing phase, reagents, including fluorescently marked nucleotides, are included, and the initial base is added. The stream cell is images, and the reach cluster’s emission is recorded. The emission wavelength, as well as intensity, are utilized to determine the base. This cycle should be repeated “n” times to generate a read length of “n” bases. Lastly, the alignment and data analysis stage involves aligning the reads with the bioinformatics package’s reference sequence. After alignment, the discrepancy between the newly sequenced read and the reference genome can be determined (Illumina, 2015).
Potential Barriers, Assumptions, and Limitations
A critical potential barrier to clinical next-generation sequencing is the absence of comparative significance assigned to respective difficulties addressing the Food and Drug Administration (FDA) regulation. There is also the lack of a standardized approach for reporting next-generation sequencing outcomes. The challenge could relate to identifying which reports are communicating, how to communicate outcomes effectiveness, or to whom the results need to be communicated. It is assumed that advanced sequencing tools could rapidly generate extensive genomic information amounts with increasing cost efficiency. The advances potentiate a significant promise for incorporating genomics into healthcare for employment with precision practice. Nevertheless, they also undermine the conventional policy structures for intellectual property, regulation, coverage, and reimbursement (Messner et al., 2017).
Outcome Impact
The evidence-based practice of next-generation sequencing in establishing the resistant genes in microbes is better than antibiotics. The antibiotics have proved unreliable because of the prevalence of antimicrobial resistance to virtually all antibiotics. In that vein, using next-generation sequencing to determine resistance genes within microbes instead of antibiotics would enhance professional expertise, quality care improvement, and patient-centered quality care. In the same way, the outcome would ensure that next-generation sequencing is employed within healthcare practice to personalize therapies and enhance care outcomes for cancer patients. In terms of professional experience, precision medicine would use genomic data to offer the appropriate treatments to the appropriate patient conveniently. Regarding processes efficiency, next-generation sequencing allows healthcare professionals to accurately and rapidly sequence many genes simultaneously. In addition, environmental scientists also use next-generation sequencing to determine how species respond to climate changes (Morash et al., 2018).
Section D: Implementation Plan
Part 1: Application of an Evidence-Based Practice (EBP) Model– Rogers’ Diffusion of Innovation Theory
Antimicrobial resistance is a global health issue that is negatively affecting people and health systems. India is the most affected region with an average rate of 57 percent of Carbapenems compared to Europe, recoding below five percent (Laxminarayan & Chaudhury, 2016). Failure to address antimicrobial resistance to the Carbapenems is more likely to result in deaths and other health-related complications. Therefore, these startling statistics are a clarion call for adopting an ideal approach that will see the issue in question is appropriately mediated. In this case, the adoption of next-generation sequencing to address antimicrobial resistance is the most sought approach to yield positive results. This approach is verified supported by a plethora of studies and evidence-based models. Rodgers’ diffusion of innovation theory perfectly elaborates how adopting next-generation sequencing (NGS) can mitigate the antimicrobial resistance menace in India and society.
In its simplest form, diffusion of innovation refers to people’s process when adapting to a new idea, practice, or product (Kaminski, 2011). Rogers contended that few people contend with this process at its initial stages while most are skeptical (Kaminski, 2011). Further, this model concedes that most of the targeted audience must be well informed for an approach to be successful. Therefore, there needs to be a continuous discussion about innovation and its positive impacts on society in this case. For example, in this context, the adoption approach of next-generation sequencing can be initiated by one individual spreading the word. At the same time, more and more people join the conversation until innovation becomes more common amongst the population in India. Rogers categorized adopters of innovation into five distinct groups: innovators, early adopters, early majority, late majority, and laggards, as exhibited in figure 1 below (Kaminski, 2011). In some instances, a sixth group can be added, known as non-adopters. As evidenced in the image, each group’s percentage is estimated, similar to the segmentations present in a standard bell curve. The start point is at early adopters, while the saturation point is late adopters. This theory aims to move people within the five mentioned categories to ensure all people are at par while implementing an innovation.
Figure 1
Diffusion of Innovation Adopter Categories
Diffusion theory is an ideal concept in affecting the rate and reach. Its use is pegged on taking additional steps in the initial stages of developing innovation to have more people informed about the change. More importantly, people must positively perceive the projected innovation for swift adaptation and implementation. The significance of diffusing an innovation is to reach extended communities and population segments where change is highly needed (Dearing & Cox, 2018). This assertion relates to the innovation in question as it is most sought by the world as antimicrobial resistance...