Antimicrobial Resistance And Selective Decontamination: Critical Appraisal Of Five Studies

Antimicrobial Resistance and Selective Decontamination

Antimicrobial resistance (AMR) is commonly referred to as the ability of a microorganism to resist the impacts of medication that are generally found efficient in destroying the microbes. The term is interchangeably used with antibiotic resistance that is applied for explaining a phenomenon where bacteria display a resistance towards antibiotics. There is mounting evidence for the difficulty that is most commonly encountered while treating resistant microbes, and thus require different forms of alternative medications, in addition to increased dosage of antimicrobials (Smith & Coast, 2013). However, these approaches have been found to be expensive and toxic. In other words, microbes that are resistant to a range of antimicrobials are referred to as multidrug resistance (MDR). Although several reasons have been identified by researchers for the onset of such resistance, selective decontamination is a potential factor that contributes to the phenomenon (Roca et al., 2015). Selective digestive decontamination (SDD) refers to a procedure that is implemented in intensive care units (ICUs) with the aim of reducing the occurrence or incidence of infections among patients who are critically ill. The procedure generally involves an administration of antibiotics that effectively reduce the presence of fungi and bacteria in the digestive tract (Price, MacLennan & Glen, 2014). This directly prevents the microbes from creating illness among people who have been found at an increased risk. Furthermore, selective decontamination affects both abnormal and normal flora (Huttner et al., 2013). This essay will critically analyse five articles that focus on selective decontamination and its correlation with antimicrobial resistance.

Methods: A research question is often considered as an essential aspect of a literature review or a research study and generally elaborates on the study by determining the prime methodology, and guides the inquiry and/or reporting of relevant findings. The research question for the current study was:

Is there an association between selective decontamination and antimicrobial resistance among critically ill patients?

The literature search was a two-step procedure. Initially an exhaustive research was conducted in Google Scholar for extracting articles that were relevant to the research question. Following extraction of articles from the database, the titles and abstracts were read in order to determine whether those that were supposed to be included in the appraisal were pertinent to the formulated question. Inclusion criteria comprised of the following:

• Articles published in English
• Methodologically sound
• Publication year between 2010-2018
• Focuses on selective decontamination

After addition of the aforementioned filters, five articles were selected. These five articles were evaluated for their full text and the bibliography as well. The search results indicated that there exists a wide array of scholarly papers that focus on the impacts of selective decontamination on antimicrobial resistance in ICU patients. Use of different Boolean operators such as, ‘OR’ and ‘AND’ greatly facilitated obtaining accurate search results (McGowan et al., 2016). These Boolean operators helped to combine the key terms that were ‘antimicrobial’, ‘resistance’, ‘selective’, ‘decontamination’, ‘antibiotic’, ‘AMR’, ‘ICU’, ‘patients’, ‘hospitals’, ‘effect’, ‘impact’, and ‘relation’ (Aromataris & Riitano, 2014). Following selection of the five articles, the CASP tool was used for analysing them. This was followed by the use of FORM body of matrix for determining the level and/or standard of evidence.

Methodology

Results: Five articles were selected that successfully addressed the research question that was formulated for the study. Out of these five, two were cohort studies, one was a systematic review, and two were RCTs. The analysis done for ach study is given below in the table 1. This analysis was done with the help of the CASP checklist (Munn et al., 2014). These checklists are an essential critical appraisal tool that are used for assessing a particular published research. It primarily illustrates the importance of applying a set of rules of evidence for determining the internal validity of the studies, besides determining their adherence to certain reporting standards. Most of the questions in the study were answered as either ‘yes’, ‘no’ or ‘can’t tell’. Furthermore, there were certain open ended questions as well that required a clear explanation of application of the findings to the local context. The NHMRC Body of evidence matrix was used for determining the strength of evidence of each of the articles (Mja.com.au, 2018). This was an explicit and systematic approach for making decisions about the superiority of evidence and the forte of recommendations. The use of this guideline facilitated critical assessment of the judgments, thereby creating the provision for making future recommendations.

Questions	de Smet et al., (2011)	Oostdijk et al., (2014)
1. Did the trial address a clearly focused issue?	Yes	Yes
2. Was the assignment of patients to treatments randomised?	Yes	Yes
3. Were all of the patients who entered the trial properly accounted for at its conclusion?	No	Yes
4. Were patients, health workers and study personnel ‘blind’ to treatment?	Can’t tell	Can’t tell
5. Were the groups similar at the start of the trial?	Yes	Yes
6. Aside from the experimental intervention, were the groups treated equally?	Yes	Yes
7. How large was the treatment effect?	Significant	Significant
8. How precise was the estimate of the treatment effect?	Precise	Not precise
9. Can the results be applied in your context? (or to the local population?)	Yes	Yes
10. Were all clinically important outcomes considered?	Yes	Yes
11. Are the benefits worth the harms and costs?	Yes	Yes

Table 1- Appraisal of RCTs

Questions	Sánchez-Ramírez et al., (2018)	Noteboom et al., (2015)
1. Did the study address a clearly focused issue?	Yes	Yes
2. Was the cohort recruited in an acceptable way?	Yes	No
3. Was the exposure accurately measured to minimise bias?	Yes	Yes
4. Was the outcome accurately measured to minimise bias?	Yes	Yes
5. (a) Have the authors identified all important confounding factors?	Yes	No
5. (b) Have they taken account of the confounding factors in the design and/or analysis?	Can’t tell	Yes
6. (a) Was the follow up of subjects complete enough?	Yes	Yes
6. (b) Was the follow up of subjects long enough?	Yes	Yes
7. What are the results of this study?	SDD treatment duri8ng 4yars was found effective in ICU with high resistance level	Acquisition rates for antibiotics that were systematically administered were comparable among patients subjected to standard care and selective decontamination.
8. How precise are the results?	Precise	Precise
9. Do you believe the results?	Yes	Yes
10. Can the results be applied to the local population?	Yes	Yes
11. Do the results of this study fit with other available evidence?	Yes	Yes
12. What are the implications of this study for practice?	The rates of infection can get considerable reduced	Quantification can help in gaining a better understanding of resistance acquisition among SOD or SSD treated patients

Table 2- Appraisal of Cohort studies

Questions	Daneman et al., (2013)
1. Did the review address a clearly focused question?	Yes
2. Did the authors look for the right type of papers?	Yes
3. Do you think all the important, relevant studies were included?	Yes
4. Did the review’s authors do enough to assess quality of the included studies?	Yes
5. If the results of the review have been combined, was it reasonable to do so?	Yes
6. What are the overall results of the review?	No correlation between SOD and SSD administration and antimicrobial resistance
7. How precise are the results?	Can’t tell
8. Can the results be applied to the local population?	Yes
9. Were all important outcomes considered?	Yes
10. Are the benefits worth the harms and costs?	Yes

Table 3- Appraisal of systematic review

Below given is the table for the NHMRC Body of evidence matrix, where the major results of the literature selected in the previous section are highlighted.

Component	Excellent (A)	Good (B)	Satisfactory (C)	Poor (D)
Evidence Base	One or more level I studies with a low risk of bias or several level II studies with a low risk of bias	One or two level II studies with a low risk of bias or an SR/several level III studies with a low risk of bias	One or two level III studies with a low risk of bias, or level I or II studies with a moderate risk of bias	Level IV studies, or level 1 to II studies/SRs with a high risk of bias
Consistency	All studies consistent	Most studies consistent and inconsistency may be explained	Some inconsistency reflecting genuine uncertainty around clinical question	Evidence is inconsistent
Clinical Impact	Very large	Substantial	Moderate	Slight or restricted
Generalizability	Population/s studied in body of evidence are the same as the target population in the guideline	Population/s studied in the body of evidence are similar to the target population for the guideline	Population/s studied in the body of evidence differ to the target population guideline but it is clinically sensible to apply this evidence to the target population	Population/s studied in the body of evidence differ to the target population and hard to judge whether it is sensible to generalize to target population
Applicability	Directly applicable to Australian healthcare context	Applicable to Australian health care context with few caveats	Probably applicable Australian healthcare context with some caveats	Not applicable to Australian healthcare context

Table 4- Grading system

Thus, the FORM ranking for the level of evidence is B, which is a direct indication of the fact that the body of literature can be easily trusted for guiding medical practice in most healthcare situations that encompass antimicrobial resistance.

Discussion: Randomised controlled trials are one of the most rigorous ways that help in the determination of the cause-effect relation between an implemented treatment and the outcome measures. This directly helps to evaluate the effectiveness of a particular treatment procedure. Some of the primary benefits of such RCTs are that they minimize all forms selection bias and allocation bias (De Serres et al., 2013). Thus, minimization of selection bias allows a comparison between different groups, thus evaluating the effects of a particular treatment when compared to a control group, upon controlling the variables. However, systematic reviews are also considered as a reliable evidence source owing to the fact that they comprise of studies that are able to clearly address the research question (Moher et al., 2015). Since the conclusion of such reviews are more dependable than individual studies, one such review was also included in the critical appraisal. Inclusion of two cohort studies can be explained by the fact they comprise of a group of individuals who commonly share a similar characteristic and possibly experience some common event, in relation to the research question. This provides an explanation for the inclusion of RCTs, systematic reviews and cohort study in the appraisal.

Results

Upon interpreting the CASP checklist of the selected articles there were various similarities obtained (Pocock, 2013). The major similarity was that all the articles were successful in clearly addressing the issues related to antibiotic resistance. There is mounting evidence for the fact that antibiotic resistance generally occurs when the bacteria acquire the capability of defeating or destroying drugs that have been formulated to kill the former. All the individuals recruited at the beginning of the study showed similarity in their exposure to SOD or SSD. The primary aim of both the approaches that the patients were subjected to, is to potentially eradicate pathogens with the use of prophylactic non-absorbable antibiotics in the gastrointestinal tract or the oropharynx. Thus, the similarity of the participants in their characteristics were effective in bias removal. Blinding often refers to concealing group allocation from participants or researchers in a clinical research. This process is generally followed for preventing differential treatment between the groups at the end of a trial, thereby reducing chances of bias in the treatment impacts.

However, no accurate information was provided in the two RCTs regarding blinding or concealment, thereby providing a scope of misleading or unreliable results, due to moderate bias. All, except one study were successful in confirming significant association between selective decontamination and antibiotic resistance among patients. Oostdijk et al., (2014) provided evidence that unit-wide implementation of SOD and SDD were in association with low antibiotic resistance levels and no significant variations were observed in the day-28 mortality among the patients. Furthermore, SDD was related with reduced rectal antibiotic-resistance gram negative bacteria carriage. Conversely, SDD treatment was found beneficial in an ICU ward, with reduced resistance in another cohort study (Sánchez-Ramírez et al., 2018). Similar findings were presented by an RCT as well that formed a correlation between use of the two techniques and low antibiotic-resistance levels (de Smet et al., 2011). However, no absolute association was found between the two in the findings of the systematic review (Daneman et al., 2013). Thus, taken together, the findings of the systematic review, and the individual studies provide a strong indication for the protective actions of SOD and SDD against antibiotic resistance among patients who are critically ill.

Interpretation of FORM: The FORM framework acts as a guideline that provides a structured and ordered process for taking into account an entire body of evidence that is relevant to the research question being investigated. The five criteria against which the studies were evaluated are as follows:

1. Level of evidence- The quality of the studies were determined in relation to an assessment of the risk of bias that were present in the way the study was conducted, designed or reported. The NHMRC Evidence Hierarchy has identified systematic reviews as evidences of level I. Thus, the systematic review included in the research was of the highest evidence, in terms of the association between antibiotic resistance with SSD and SOD (Mja.com.au, 2018). The two cohort studies that were included in the review were of level III-2, as per the hierarchy table. This was in clear contrast with the fact that randomised controlled trials belong to level I.  Hence, the critical appraisal comprised of scholarly papers that were in accordance to three different hierarchical levels, thereby placing them in the (C) category, due to the moderate bias risks associated with the studies.
2. Consistency- This was calculated by determining whether the findings were in accordance to each other (Mja.com.au, 2018). Except one study that failed to establish an association between antibiotic resistance and selective decontamination, others presented similar findings. Thus, consistency is being given a grade (B) (Rychetnik et al., 2002).
3. Clinical impact- This is most commonly associated with the measurement of the likely benefit that an intervention will create on the target population, and is one of the most subjective evidence components (Mja.com.au, 2018). The fact that SSD and SOD were found important in reducing the severity and levels of antibiotic resistance in patients admitted to ICUs, helped in placing it in grade (B) (Coleman et al., 2005).
4. Generalizability- This was determined by assessing the precision of the available evidence in providing answers to the research question being investigated (Mja.com.au, 2018). Grade (B) was placed regarding generalisation of the obtained findings since almost all the studies comprised of settings and participants that were in complete match with the patient population being studied (Coleman et al., 2005). Since antibiotic resistance is most commonly observed among patients who have been admitted to acute wards in hospitals, the study results could be easily generalised.
5. Applicability- Relevance of the evidence base to the Australian healthcare system was evaluated in this component (Mja.com.au, 2018). However, there exist huge differences in the way by which healthcare and illness are perceived in different countries. Therapeutic and diagnostic procedures are perceived in dissimilar forms in varied cultures and the alterations in beliefs in the developing countries might not be appreciated in a similar context in Australia (Cutler et al., 2013). Since the studies were conducted upon patients belonging to different geographical regions, difficulties might be encountered while implementing the SDD and SOD procedures, in regards to access to resources, funding and general perceptions. This resulted in a grade of (C).

Discussion

The implications of level B grade of evidence are quite large in healthcare and medicine practice. The meanings constructed from the data helped in gaining an idea about the reliability of the results in future practice. Antibiotic resistance has been identified as one of the major threats to global health, development and food security (Ventola, 2015). This condition has been found to create an impact on people belonging to all age groups, regardless of their geographical origin. Furthermore, antibiotic resistance has also been found to impede the treatment of tuberculosis, gonorrhoea, pneumonia, salmonellosis, among other illnesses. Thus, the findings from the collected evidences are relevant in medical and nursing practice, due to its potential role in enhancing the health and overall wellbeing of the patients. Antibiotics are generally used for the prevention and management of bacterial infections (Laxminarayan et al., 2013). However, resistance to these antibiotics occur when there occurs a change in the bacteria, in response to the medications.

Due to the fact that antibiotic resistance results in an increase in the length of hospitalization, medication costs, and increased mortality, the establishment of a correlation between selective decontamination and reduced resistance is highly impactful in current practice (Smith & Coast, 2013). There needs to be a huge change in the ways by which antibiotics are prescribed and used (McArthur et al., 2013). Thus, even with a development of medicines, antibiotic resistance will pose major threats to health and wellbeing, without implementation of adequate behavioural changes. The fact needs to be considered that antibiotic resistance is experiencing a dramatic increase in different parts of world, due to the emergence and spread of novel resistance mechanisms, on a global scale. This directly threatens the ability of patients admitted to ICUs to fight against infectious diseases. Under situations where the antibiotics can be commonly bought for humans, without the presence of an appropriate prescription, the spread and emergence of such resistance become worse. Similarly, healthcare workers in countries that do not have adequate guidelines and framework for treatment often encounter situations where the antibiotics are over prescribed, for use in the public.

Thus, without adequate action, common infections and injuries might prove fatal for the public. The findings related to selective decontamination will prevent the misuse and/or overuse of antibiotics, thereby reducing the acceleration of antibiotic resistance. Similar steps can be taken by the healthcare authorities in Australia to eliminate the impacts of antibiotic resistance, by limiting or restricting its spread. Policy makers will also play an essential role in future practice in the prevention and control of the extent of antimicrobial resistance among critically ill patients. They will have to formulate and implement a robust action plan at the national level for tackling antibiotic resistance, with the aim of improving the surveillance of antimicrobial resistant infections. Strengthening the healthcare programs and policies and implementing control and prevention measures. Furthermore, making adequate information available to the public on antibiotic resistance will greatly facilitate tackling the problem.

Conclusion

Conclusion:

On a concluding note, the purpose of this research study had been to discover if there is any considerable association between the concept of selective decontamination and the antimicrobial resistance that the critically ill patients are capable of exhibiting. As per the implicative benefits with respect to clinical application, the data suggested that antibiotic resistance is undoubtedly a global threat and is one of the primary contributing factors leading to prolonged hospital stays and costs by impeding the treatment for most of the severe infectious diseases. From the results of the extensive research and evidence based comparative analysis, there is a significant link between the selective decontamination and the reduced resistance in the critically ill patients. Hence, it is crucial to refine the use of antibiotic medication among the patients along with the general behavioral patterns associated with the use of antibiotics. A grave concern associated with this issue is the fact that there is an acute lack of awareness among the general population about the overuse and casual usage of antibiotics without medical supervision, its association with antimicrobial resistance and the perilous impact of the same. It is clear that there is need of increased health education of the population with respect to antibiotic use to reform the casual behavior of the patient populations. With more research on the perception of the general people on antibiotic use and the risk of antimicrobial resistance, definite factors can be recognized to help design and implement educational campaigns to aware people of the threat.

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