A systematic synthesis of expert opinion on effective policies to tackle bacterial resistance worldwide

Abstract Actions that are taken to preserve effective antibacterial agents and eliminate transmission of resistant organisms are crucial to prevent a catastrophic postantibiotic era. In this systematic review, we searched and appraised relevant texts and expert opinions to determine effective strategies to tackle bacterial resistance worldwide. We considered expert opinions, consensus, current discourses, comments, assumptions or assertions and discussion papers published in English. We searched following databases for expert opinion‐based literature: MEDLINE, CINAHL, ISI Web of Knowledge, SCOPUS, Cochrane Central Register of Controlled Trials and World Health Organization (WHO). We extracted the textual data from texts using a standardised data extraction tool. Textual pooling was not possible, so the conclusions were presented in a narrative form. Eighteen texts were included in this review. The findings show that, the most repeated policies and strategies include implementing and strengthening bacterial resistance surveillance, developing national guidelines, improving public awareness; enhancing home and everyday life hygiene; improving prescribing patterns, improving laboratories capacity, promoting innovation and research in new drugs and technology and strengthening coordination. This review systematically gathered strategies that were recommended by textual publications. To our knowledge, this was the first systematic review of text and opinion in the field of bacterial resistance. These results can be used by policymakers, hospital managers, and governments, alongside the results of quantitative and qualitative systematic reviews.

a systematic review indicated that antibiotic use without a prescription of correct diagnosis of a bacterial infection occurred worldwide and accounted for 19-100% of antimicrobial use outside of northern Europe and North America (Morgan et al., 2011). This study also revealed that antimicrobial-resistant bacteria were common in settings with frequent nonprescription use (Morgan et al., 2011).
One of the most concerning factors related to microbial resistances is its high clinical and economic burden. The societal cost of antibiotic resistance attributable to each ambulatory antibiotic prescription in the United States was estimated to be 13$, of which 69% was due to the cost of hospitalisation (Michaelidis et al., 2016). Based on the results of a study, medical expenses of antimicrobial-resistant infections ranged from 18,588$ to 29,069$ per patient; hospital stay days were longer for these patients being about 6.4−12.7 days; and societal costs were 10.7$−15.0$ (Roberts et al., 2009).
The World Health Organization (WHO) has recommended a global effort focusing on a multisectoral approach and collaboration among WHO, the Food and Agriculture Organization (FAO), and the World Organization for Animal Health (OIE) in the spirit of the 'One Health' approach (WHO, 2014). The reason for this collaborative approach is that people, animals and environmental and agricultural factors are the main drivers of antimicrobial resistance (Mcewen & Collignon, 2018).
The One Health approach involves strong communication and coordination among the representatives of these three sections (Lammie & Hughes, 2016).
Due to the value of systematic review of expert opinion, the current systematic review of text and expert opinion was conducted to investigate expert's opinions, thoughts, and conclusions regarding bacterial resistance. This type of systematic review can stand alone or be used alongside quantitative or qualitative systematic reviews. To our knowledge, this was the first systematic review of text and opinion in the field of bacterial resistance.

METHODS
For our systematic review, we adhered to a unique methodology for the review of text and opinion (Mcarthur et al., 2015). In this type of systematic review, the opinions of experts, which has an important role in evidence-based policymaking, are gathered and assessed. Evidence of text and opinion in this type of systematic review comes from expert opinions, consensus, current discourse, comments, assumptions or assertions that come in journals, magazines or reports (Mcarthur et al., 2015).

Assessment of methodological quality
Textual papers selected for retrieval were assessed by two independent reviewers (NK and HA) for methodological quality using standardised critical appraisal instruments. This tool has six questions: Is the source of opinion clearly identified? Does the source of opinion have standing in the field of expertise? Are the interests of the relevant population the central focus of the opinion? Is the stated position the results of an analytical process and is this logic in the opinion expressed? Are there references to the extant literature? Is any incongruence with the literature/sources logically defended? Any disagreements between the reviewers were resolved through discussion, and in some cases, they were referred to the third reviewer. The reviewers considered the papers with a score of four and above as high-quality paper.

Text selection
Following the search, all identified citations were collated and uploaded into Endnote software, and duplicates were removed. Titles and abstracts were screened by two independent reviewers (NK and HA), considering the inclusion criteria. Texts that met the inclusion criteria were retrieved in full. Full texts that did not meet the requirements of the inclusion criteria were excluded. Included texts underwent a process of critical appraisal. Disagreements between reviewers were resolved through discussion or with a third reviewer (SH).

Textual data extraction
Textual data were extracted from included texts in the review using a standardised data extraction tool, which includes specific details about the policies, populations, context and type of text.

Textual data synthesis
The aim of textual synthesis is to establish synthesised findings by bringing together key conclusions drawn from included texts. The conclusions were presented in narrative form. Two of the reviewers (NK and LD) read and re-read the conclusions in order to identify similarities that can then be used to create categories of more than one finding.
We used content analysis (Stemler, 2015) to categorise the findings into themes, counting and converting these themes into frequencies to identify dominant policies to tackle microbial resistance across a number of included texts.

RESULTS
The primary search yielded 856 texts. After removing duplicates using bibliographic software (Endnote), 773 records remained. Title and abstract screening reduced this record to 49 documents. Of these, 31 were excluded due to noncompliance with the inclusion criteria. Finally, 18 texts were included in the review based on inclusion/exclusion cri-teria and methodological quality assessment. After full text review, the most common reasons for exclusion were as follows: (1) the document question did not meet the aim of systematic review and (2) they were a research article. Figure 1 is a PRISMA 2020 flow diagram of the study selection and inclusion process. Based on the predetermined method for quality assessment, all of the included documents had high quality and were included in the study.

Review findings
The process of content analysis yielded 132 themes. Five target audiences and settings were found based on the results of included text.  (Simonsen, 2009). In Thailand, a surveillance program has led to a cost-effective approach to the treatment of diseases without risk of resistance (Shrivastava et al., 2016). Another antimicrobial surveillance system designed in the Netherlands has provided impor-  (Cui et al., 2017). In addition, it seems to be helpful to implement these guidelines with financial incentives.
One of the included documents in the current review was the 'WHO global strategy for containment of antimicrobial resistance' , in which advocacy, education, management, and regulation of drug use were provided (WHO, 2001). One study assessed the advantages of this global report including, simple and comprehensive interventions provided in the program, and its generic framework, which can be applied to specific diseases such as HIV and malaria (Simonsen et al., 2004).
The other report by WHO included in the current review, which was announced on 2011 world health day (WHO, 2011), had been used as an interview questionnaire in on study by The Western Pacific Regional Office of WHO (Lee & Wakabayashi, 2013). The results of the study showed that policymakers in the area of antimicrobial resistance were widely alert and knowledgeable about antimicrobial resistance.
In the present study, we found that patient and public awareness is one of the policies for reducing bacterial resistance. Nepal and Bhatta (2018), in their recent systematic review, showed that selfmedication with antibiotics is very high in the WHO Southeast Asian region, which is one of the leading causes of microbial resistance. Jamhour et al. (2017) indicated that there was a significant correlation between self-medication and educational level. Notably, the trend of self-medication with antibiotics has changed since the novel coronavirus disease (COVID-19) emerged. Preventive use of antibiotics against COVID-19 was a result of a lack of understanding regarding the effects of antibiotics (Zhang et al., 2021).
As the results of the current systematic review show, there is a need for research on new medicines as a complement to antibiotics. Enioutina et al. (2017) indicated that natural products and herbal antimicrobial drugs could be advantageous in treatment. However, there is a need for more research on the efficacy and safety of these drugs (Enioutina et al., 2017). Dandekar proposed closer cooperation between pharmaceutical industries and basic research to turn research into new drugs (Dandekar & Dandekar, 2010).

Strengths and limitations of the study
This study provides an unprecedented opportunity to develop integrated efforts from experts' opinions to better inform the design and improvement of bacterial resistance in the health system context, which expands the basis for evidence-informed policymaking (Hasanpoor et al., 2018). This study has limitations. We adopted a systematic search strategy of texts and expert opinions to identify all related studies; however, some might have been missed.

CONCLUSIONS
Governments and

Management, guidelines and formularies
2.6 Improve antimicrobial use by supervision and support of clinical practices, especially diagnostic and treatment strategies. 2.7 Audit prescribing and dispensing practices and utilise peer group or external standard comparisons to provide feedback and endorsement of appropriate antimicrobial prescribing. 2.8 Encourage development and use of guidelines and treatment algorithms to foster appropriate use of antimicrobials. 2.9 Empower formulary managers to limit antimicrobial use to the prescription of an appropriate range of selected antimicrobials.

Regulation
2.10 Link professional registration requirements for prescribers and dispensers to requirements for training and continuing education.

Hospitals Management
3.1 Establish infection control programmes, based on current best practice, with the responsibility for effective management of antimicrobial resistance in hospitals and ensure that all hospitals have access to such a programme. 3.2 Establish effective hospital therapeutics committees with the responsibility for overseeing antimicrobial use in hospitals. 3.3 Develop and regularly update guidelines for antimicrobial treatment and prophylaxis, and hospital antimicrobial formularies. 3.4 Monitor antimicrobial usage, including the quantity and patterns of use, and feedback results to prescribers. (Continues)

Author (year) Type of text
Target audiences of policy recommendations Geographical setting Content of the policy Diagnostic laboratories 3.5 Ensure access to microbiology laboratory services that match the level of the hospital, e.g. secondary, tertiary. 3.6 Ensure performance and quality assurance of appropriate diagnostic tests, microbial identification, antimicrobial susceptibility tests of key pathogens, and timely and relevant reporting of results. 3.7 Ensure that laboratory data are recorded, preferably on a database, and are used to produce clinically and epidemiologically useful surveillance reports of resistance patterns among common pathogens and infections in a timely manner with feedback to prescribers and to the infection control program Interactions with the pharmaceutical industry 3.8 Control and monitor pharmaceutical company promotional activities within the hospital environment and ensure that such activities have educational benefit. 4. Use of antimicrobials in food-producing animals 4.1 Require obligatory prescriptions for all antimicrobials used for disease control in food animals. 4.2 In the absence of a public health safety evaluation, terminate or rapidly phase out the use of antimicrobials for growth promotion if they are also used for treatment of humans. 4.3 Create national systems to monitor antimicrobial usage in food animals. 4.4 Introduce prelicensing safety evaluation of antimicrobials with consideration of potential resistance to human drugs. 4.5 Monitor resistance to identify emerging health problems and take timely corrective actions to protect human health. 4.6 Develop guidelines for veterinarians to reduce overuse and misuse of antimicrobials in food animals.
WHO 2011 WHO recommendations on world health day