Tackling antimicrobial resistance in Bangladesh: A scoping review of policy and practice in human, animal and environment sectors

Background Antimicrobial resistance (AMR) has become an emerging issue in the developing countries as well as in Bangladesh. AMR is aggravated by irrational use of antimicrobials in a largely unregulated pluralistic health system. This review presents a ‘snap shot’ of the current situation including existing policies and practices to address AMR, and the challenges and barriers associated with their implementation. Methods A systematic approach was adopted for identifying, screening, and selecting relevant literature on AMR situation in Bangladesh. We used Google Scholar, Pubmed, and Biomed Central databases for searching peer-reviewed literature in human, animal and environment sectors during January 2010-August 2019, and Google for grey materials from the institutional and journal websites. Two members of the study team independently reviewed these documents for inclusion in the analysis. We used a ‘mixed studies review’ method for synthesizing evidences from different studies. Result Of the final 47 articles, 35 were primary research, nine laboratory-based research, two review papers and one situation analysis report. Nineteen articles on human health dealt with prescribing and/or use of antimicrobials, five on self-medication, two on non-compliance of dosage, and 10 on the sensitivity and resistance patterns of antibiotics. Four papers focused on the use of antimicrobials in food animals and seven on environmental contamination. Findings reveal widespread availability of antimicrobials without prescription in the country including rise in its irrational use across sectors and consequent contamination of environment and spread of resistance. The development and transmission of AMR is deep-rooted in various supply and demand side factors. Implementation of existing policies and strategies remains a challenge due to poor awareness, inadequate resources and absence of national surveillance. Conclusion AMR is a multi-dimensional problem involving different sectors, disciplines and stakeholders requiring a One Health comprehensive approach for containment.


Background
Antimicrobial resistance (AMR) has become an emerging issue in the developing countries as well as in Bangladesh. AMR is aggravated by irrational use of antimicrobials in a largely unregulated pluralistic health system. This review presents a 'snap shot' of the current situation including existing policies and practices to address AMR, and the challenges and barriers associated with their implementation.

Methods
A systematic approach was adopted for identifying, screening, and selecting relevant literature on AMR situation in Bangladesh. We used Google Scholar, Pubmed, and Biomed Central databases for searching peer-reviewed literature in human, animal and environment sectors during January 2010-August 2019, and Google for grey materials from the institutional and journal websites. Two members of the study team independently reviewed these documents for inclusion in the analysis. We used a 'mixed studies review' method for synthesizing evidences from different studies.

Result
Of the final 47 articles, 35 were primary research, nine laboratory-based research, two review papers and one situation analysis report. Nineteen articles on human health dealt with prescribing and/or use of antimicrobials, five on self-medication, two on non-compliance of dosage, and 10 on the sensitivity and resistance patterns of antibiotics. Four papers focused on the use of antimicrobials in food animals and seven on environmental PLOS

Introduction
The world is on the verge of sliding back to 'pre-antibiotic era' due to evolving resistance against life-saving antimicrobial drugs, with fundamental effect on individual and public health [1]. To combat this emerging global threat in a comprehensive manner, the World Health Organization (WHO) launched a Global Action Plan (GAP) in 2015 based on a 'One Health' approach-emphasizing the interdependence of human health, animal health, and the environment [2]. Recently, the interconnectedness of combating antimicrobial resistance (AMR) and achieving Universal Health Coverage (UHC) by 2030 has also been emphasized [3]. The southeast Asia is considered to have the highest risk of AMR among all the WHO regions [4]. Most of the countries in this region have some policy structure (either policy-inplace or policy-in-making) regarding the use of antimicrobials in food animals and fish. For example, the use of antimicrobials is banned as a food additive in some of these countries for rearing food animals, but implementation remains a problem due to the weak regulatory regime [5]. This is also true for policies to prevent contamination of the environment with antimicrobial residues from human and animal use [6].
In many of these countries, antimicrobials are widely available as over-the-counter (OTC) drug, Bangladesh is no exception [7]. The presence of a 'pluralistic' health system involving unqualified providers in the informal sector complicates the situation [8]. This is aggravated by the aggressive and unethical marketing practices of the pharmaceutical companies [9]. The regulatory regime in Bangladesh is weak concerning human, technical and logistic capacity to oversee this vast market [10].
Policies and regulations that support appropriate and rational use of antimicrobials are essential for effective interventions to contain the development and spread of AMR. Bangladesh has recently approved a National Action Plan (NAP) for containing AMR, in alignment with the WHO GAP guidelines [11]. For implementation of NAP, detailed information on the current AMR situation in Bangladesh in the human, animal and environment sectors is needed for concerted and coordinated actions across the sectors. Some small-scale studies reported patterns of antimicrobial prescription and use, non-compliance of dosage and development of resistance, and strategies to contain it in different sectors in Bangladesh; however, none so far has looked into the matter comprehensively. This scoping review aimed to fill-in this knowledge gap by examining the nature and extent of the problem in different sectors (human, animal, and environment) in Bangladesh, and exploring how the AMR issue is addressed in policy and practice and associated challenges and opportunities, and how it can be contextualized in the larger paradigm of 'One Health' for comprehensive tackling of this public health emergency.

Methods
To conduct this scoping review, we developed a protocol which specified the study objectives, research questions, inclusion/exclusion criteria, and data sources/search engines to be used (Google for unpublished/grey materials; Google Scholar, PubMed, and BioMed Central for peer-reviewed articles) ( Table 1). We hand searched for relevant grey materials/unpublished documents from the institutional and journal websites. The key search terms were fixed, for all three sectors such as human, animal and environment ( Table 2). A PRISMA extension for Scoping Reviews (PRISMA-ScR) checklist was filled-in to complete this report (S1 Table).
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach for selection of articles on current AMR situation and relevant policies and practices to be included in the analysis (Fig 1).

Objectives
Synthesis of evidence on current scenario of antimicrobial use and misuse in all sectors in Bangladesh, level and extent of AMR, programmes/innovations for combating AMR including existing and emerging policies and practices Synthesis of evidence on challenges and opportunities to combat AMR in Bangladesh by identifying barriers and facilitators Make recommendations to inform policy and practice for combating AMR in Bangladesh based upon findings from literature review and from the perspective of One Health

Research Questions
What is the current scenario regarding use of antimicrobials among different population groups that predisposes to the emergence of AMR in Bangladesh? In the food animals and fishes? Contamination of environment and the food cycle?
What are the level and pattern of AMR in different geographic regions of Bangladesh?
What initiatives/stewardship/surveillance/other programmes have been taken to contain AMR in Bangladesh? The role of One Health approach to address the AMR problem?
What are the legal and policy frameworks including national action plan to combat AMR in Bangladesh?
Search Strategy Inclusion Criteria AMR related study conducted in Bangladesh (e.g. use and misuse, AM related knowledge and practice including demand and supply side factors, existing AMR policies and strategies, AM use guidelines and stewardship programmes, AMR surveillance, One Health framework, etc.)

Data extraction and analysis
We used a 'mixed studies review' method for synthesizing evidence from qualitative, quantitative and mixed method studies which are useful in understanding complex public health interventions and programmes [12]. A data extraction matrix was used for organizing data, disaggregated into three key themes e.g., current antimicrobial situation (prescribing pattern, use and compliance); perception regarding irrational use of antimicrobials and emergence of AMR (providers, users); and current policies and practices related to antimicrobial use, including relevant sub-themes under each category ( Table 3). The study team members critically appraised the selected articles under the guidance of principal investigator, as per PRISMA checklist. Studies that mainly focused on antimicrobial resistance in the human, animal and environment sectors in Bangladesh were included for analysis. Differences in thematic (or sub-thematic) categorization or interpretation of the evidences were resolved by discussion among the study team members under the supervision of the senior investigator to reach a consensus with additional revisions as deemed necessary.

Results
We used Google, Google Scholar, Pubmed, and BiomedCentral databases for searching relevant literature from Bangladesh. Ultimately, 47 articles (AMR situation in human health = 36 and AMR situation in animal and environment = 11) were included for analysis. Of these, 35 were primary research, nine laboratory-based research, two review papers and one situation analysis report. Again, 19 of the articles on human health dealt with antimicrobial prescribing and/or use, five with self-medication, two on non-compliance of dosage, and 10 were on antibiotics sensitivity and resistance patterns. For AMR scenario in animals and environment, five papers focused on use in animals and six papers on environmental contamination. Besides, current health and drug-related policies and strategies for both humans and animals, and national action plan for containment of AMR in Bangladesh were included through hand search and grey literature search using Google. The findings from the review are described below according to key themes of the study.
AMR situation in humans: (Table 4) Prescribing pattern, use. Several small-scale studies reported on antimicrobial prescribing and its use, varying by factors such as age and sex. For example, children (66%) were prescribed more antimicrobials than adults (44%) [13], and the rate of prescribing antimicrobials was higher at the extremes of ages [14], and for males [15]. Higher-generationantimicrobials (e.g., ceftriaxone, ciprofloxacin, azithromycin) were prescribed quite frequently [14,16,28,31], especially by the physicians [16]. A study from a slum in Dhaka shows that awareness-building education may improve rational use of antimicrobials, by reducing prescription generation Table 2. Key terms used for searching electronic databases.

AMR (combined by 'OR') (a) Health sector (combined by 'OR') (b) Geographic location (combined by 'OR') (c)
and/or its indiscriminate use [17]. Studies reveal two or more antimicrobials to be commonly prescribed at a time in Bangladesh [14,15,18,19,20,22,30,31], and more antimicrobials to be prescribed in hospital settings compared to community settings [21]. Prescribing antibiotics without laboratory tests was quite common in Bangladesh due to reported lack of testing facilities [18,19,22]. However, sometimes the qualified prescribers (e.g., in-service trainee doctors of medical college hospital) felt confident enough to select an appropriate antimicrobial and prescribe correct dose and duration based on clinical diagnosis [23]. This was also reiterated in a simulated patient study where antimicrobials were prescribed (71%) based on clinical acumen [24]. Qualified prescribers from some secondary and tertiary level hospitals were found to be aware of the treatment guidelines [25], but not those from the upazila (sub-district) hospitals [26]. Sometimes, standard treatment guidelines were not available [27]. Antimicrobials were commonly prescribed for fever, common cold, cough, diarrhea and ARI [16,19,26]. Non-compliance, self-treatment. Patients' non-compliance with scheduled dosage, and consequently facilitating the emergence of AMR, was a common phenomenon found in the literature reviewed [18,28,32,33]. This may be as high as 50% as patients used to stop taking antimicrobials as soon as the symptoms alleviated [18]. When prescribed antimicrobials did not work in the short-term, patients usually considered the doctors as incompetent [32,33].
The prevalence of self-treatment (taking medicine without consulting a qualified provider) in the reviewed studies was found to be quite high [33][34][35][36][37][38]. It was found to be common for illnesses such as dysentery, diarrhoea and food poisoning (36%); cold, cough and fever (28%); and presumed infection of some sort (13%) [34]. Reasons behind this self-treatment practice included advice from traditional healers (41%), prior experience with the particular antibiotic for the particular illness (33%), knowledge about antibiotics (17.5%), and waving doctors' consultation fees (1%). Besides, practice of self-medication was also found to be associated with poverty [38].
Antimicrobials sensitivity and resistance. Ten papers reported on antibiotic susceptibility testing and resistance patterns. Resistance against antibiotics like imipenem was found in uropathogens [39]. Susceptibility testing of clinical isolates demonstrated many of the common organisms such as E. coli, and S. typhi to be resistant to low-cost and commonly used antibiotics [40][41][42][43]. Mannan et al [40] collected 70 types of clinical isolates from samples of blood, sputum, urine and pus and found 64% of isolated S. typhi to be resistant to multiple antibiotics. Another study conducted in three tertiary level hospitals in Dhaka shows resistance against older and commonly used antimicrobials in E. coli, S. aureus, Pseudomonas and Klebsiella infections in 50% of the cases [41]. In 70% of cases, uncertainty about diagnosis was also The articles were chosen by searching through Google and Google Scholar; Keywords used: antibiotics, use, prescribing, resistance, and the country.

A1ntimicrobial
prescribing and/or use • 50% of outpatient prescriptions in three cities in Bangladesh had antimicrobials; 25% had more than one antibiotic prescribed; 83% were prescribed without any laboratory tests; • Non-compliance was quite high (69%); more than 50% patients stopped antimicrobials as soon as the symptoms started improving • Another study from rural health centers of Dhaka and Chittagong reported that 56% of the physicians prescribe antibiotics in suspected infection, whereas only 33% after confirmatory laboratory tests.
(Continued )    on the other hand, amikacin and cefepime were found to display higher level of sensitivity to P. aeruginosa (6.0 and 7.0, respectively).
(Continued ) a reason for prescribing excess antimicrobials. Antimicrobial sensitivity tests conducted on 2,016 culture positive urine samples from a tertiary medical college hospital in Bangladesh found E. coli in 84% of cases, which was resistant to amoxicillin in 82% of cases [42]. Similar results of low sensitivity of E. coli against amoxicillin were also observed in another study involving isolates from public and private hospitals, and clinics and diagnostic centres in Dhaka city [43]. In a recent study, Tarana et al [44] reported that Salmonella typhi was found sensitive to amikacin (70%), azithromycin (73%), ceftazidime (63%), ceftriaxone (67%) and ciprofloxacin (87%). Another study (2017) found E. coli in 86% of urine samples collected from a private medical college hospital in Dhaka which was highly resistant to amoxicillin (95%) [45]. More than 80% of MRSA isolates are also found to be sensitive to some macrolides (tobramycin, gentamycin) and carbapenem (meropenem) with resistant to ampicillin, amoxicillin, cefixime and azithromycin [46]. Antibiogram from a private sector tertiary hospital over three years (2016)(2017)(2018) shows that the last resort antimicrobials (Polymyxin B and Colistin) retained their high sensitivity to Klebsiella, Psudomonos, and E. coli [47]. A review by GARP-Bangladesh National Working Group provided a descriptive analysis of the AMR situation in different sectors along with recommendations [48].

Situation in food animals, fisheries, and environment including spread of AMR (Table 5)
A high percentage of poultry meat and eggs meant for human consumption were found to have antimicrobial residues such as tetracycline, ciprofloxacin, enrofloxacin and amoxicillin [49,50]. The prevalence of antibiotic residues varied from >60% in liver, kidney, and eggs to around 50% in breast and thigh samples [49]. In Bangladesh, 3,079 metric tons of poultry manure is produced per day and 50% of this is directly used in aquaculture [51]. For example detectable amount of oxytetracycline residues was traced in 25% Pangas fish samples from Sylhet Sadar [52]. This has resulted in the presence of pathogenic bacteria resistant to commonly used antimicrobials in water resources and salad vegetables which are significant from a public health perspective [53][54][55][56][57]. The prevalence of Salmonella species was found to vary between 60% to 78% in different street foods in Chittagong while multidrug resistant Salmonella was Antimicrobial resistance in Bangladesh Table 5. Summary of studies included for exploring different dimensions of antimicrobial resistance in animals and environment (n = 11).

Author(s), Year
Type of study Setting Themes/subthemes

Key findings
Islam S et al., 2016 [49] Crosssectional study (tissues and eggs of laying hens) Microbial inhibition test (MIT) and thin layer chromatography (TLC) were used to detect antibacterial residues Use in animal • The prevalence of antibiotic residues found 64% in liver, 63% in kidney, 56% in breast muscle, 50% in thigh muscle, and 60% in eggs • Tetracycline (48%), ciprofloxacin (46%), enrofloxacin (40%), and amoxicillin (42%) were found in liver Sattar et al., 2014 [50] Cross-sectional study (poultry muscle, kidney, liver) TLC and ultra-high performance liquid chromatography (UHPLC) method used to detect antibacterial residues Use in animal • The residues of tetracycline were 48% in livers, 24% in kidneys, 20% in thigh muscles, and 24% in breast muscles Ciprofloxacin residues were found 44% in liver, 42% in kidneys, 34% in thigh muscles and 30% in breast muscles. Enrofloxacin residues were found 40% in liver, 34% in kidneys, 22% in thigh muscles, and 18% in breast muscle Cross-sectional study A hospital-based retrospective study using clinical record sheets of goat patients (N = 1405) at a teaching veterinary hospital of Chittagong Use in animal • From anthropo-clinical analysis, 24% farmers said that they were familiar with the term 'antibiotic,' but no farmer had any ideas about antimicrobial resistance and its withdrawal period Cost of antibiotics was calculated and found to be highest (968.18-1450.04 U.S. Dollars/annum) for Gentasone plus1 (gentamicine-sulfadiazine-trimithoprime) and lowest (5.37-8.06 USD/annum) for tylosin. ) found in each of the food items tested [58]. Besides, antimicrobials were found to be used routinely to increase food animal production, resulting in the spread of antibiotic resistant organisms from farms to environment to community [53]. Around 24% of goat farmers mentioned that they were familiar with the term antibiotic but none of them had any idea about antimicrobial resistance nor withdrawal period [58]. The hospitals of Dhaka city are also contributing to the process by discharging untreated medical wastes in the water, resulting in the presence of high-levels of resistant E. coli in the water [53]. This environmental contamination contributes to wild life infections from humans and animals e.g., the presence of multidrug resistance enterococcus in free-range wildlife and Shiga Toxin-producing E.coli in Buffalo faeces [59].

Current policies and strategies to contain AMR in Bangladesh
Quite a number of policies, guidelines, ordinances and laws relevant to containment of AMR in human, food animal, and environment sectors currently exist in Bangladesh (S1 Table). Of these, seven (human = 3; animal and environment = 4) addressed the AMR issue. S1 Table: Table comparing different policies and regulations in the human, animal and environment sectors in Bangladesh. Since the updated National Drug Policy 2016 [60], the government of Bangladesh (GoB) has developed three major policy documents/guidelines with direct implications on the prevention and control of AMR in human sector: i) Pharmacovigilance and Adverse Drug Reaction (ADR) Policy 2017 for monitoring the sale and dispensing of drugs without prescription; ii) Standard Treatment Guideline (STG) for appropriate use of antimicrobials in the sub-districts; and iii) a guideline for antimicrobial stewardship developed by the country's premiere medical university (S1 Table). These policy documents dealt with different aspects of prevention and control of AMR in clinical settings.
In 2007, the Ministry of Fisheries and Livestock (MoFL) formulated the National Livestock Development Policy where they highlighted inadequate veterinary services and weak implementation of regulatory frameworks as barriers to address AMR in this sector (S1 Table). Specific laws on different aspects of food animals and fish were developed in 2010 where the use of antimicrobials, growth hormones, and pesticides were banned. For violating this law, a person might face up to one year's imprisonment or a fine of up to BDT 50,000 only (USD 650). These documents highlighted issues such as mandatory prescription for antibiotics sale, list of preferred antibiotics for illnesses of a particular system, and 1 st and 2 nd lines of choice of antibiotics for specific infecting organisms. Banning the general use of antibiotics as a growth factor is emphasized in documents pertaining to the animal sector. To prevent contamination of the environment, specific guidelines are advised for waste management e.g., Guideline for Assessment of Effluent Treatment Plant 2008, Medical Waste Management and Processing Rule 2008, and Environment Protection Act 1995. Interestingly, none of these made any specific reference to the problem of AMR (S1 Table).
Finally, a National Action Plan 2017-2022 for containing AMR in Bangladesh has been prepared by the Disease Control Unit of the Director General of Health Services, MoHFW with a road map for its implementation in alignment with the global plan [61]. The document emphasizes rational use of antibiotics in all sectors through the formulation of standard treatment guidelines, antibiotic stewardship, development of reference laboratories, Good Manufacturing Practice (GMP), Good Pharmacy Practice (GPP), infection prevention and control, and establishment of a comprehensive surveillance.

Discussion
This scoping review revealed widespread availability of antimicrobials without prescription in Bangladesh, a rising trend in its irrational use in humans and food animals and fisheries, and consequent spread of resistant strains through environmental contamination. The policies and strategies to contain AMR are at an early stage of development in the country and implementation remains a major challenge. This is due to poor awareness about AMR among the policy makers and practitioners, inadequate resources to implement measures to contain AMR, and absence of a comprehensive national surveillance system to monitor the emergence of AMR. The implications of these findings in the context of the emerging 'One Health' movement in the country is discussed, including some recommendations for tackling the problem urgently.

Supply and demand side factors facilitating the emergence of AMR
It is obvious from the findings that the factors underlying irrational and inappropriate use of antimicrobials, and consequent emergence of AMR in Bangladesh, have both supply and demand side perspectives. On the supply side, all categories of the allopathic practitioners whether qualified or not, are prone to use 'excess' antimicrobials due to poor awareness regarding its rational use. Other factors contributing to the emergence of AMR include lack of diagnostic facilities, burgeoning private practice and unreasonable demand for antibiotics from patients and 'caregivers', especially for children. Besides, there are aggressive marketing strategies of the pharmaceutical companies specifically aimed at generating prescriptions at the cost of patients. This scenario is not unlike that found in other countries of the region such as India [62], Indonesia [63], Malaysia [64], Nepal [65], and Laos [66] irrespective of specialties. Encouragingly, attempts have been made to overcome the 'gaps' in knowledge and use of antimicrobials by these countries which have implication for Bangladesh. For example, the Indian Council of Medical Research (ICMR) brought a qualified group of prescribers in a workshop to enhance their knowledge on AMR and related issues, and involved them in preparing guidelines for rational prescription of antimicrobials [67]. GARP-Nepal is working to outline the components of national strategy for prevention of AMR in Nepal [65]. Indonesia and Malaysia have national level committees to monitor antimicrobial prescription and promote its rational use [68]. These countries hosted a dedicated website for consumer awareness and education regarding rational use of antimicrobials and included schools in the campaign. Besides, the ASEAN countries also included standard treatment guidelines, pharmacovigilence and problem-based pharmacotherapy in their core medical curriculum [68].
In the demand side, rising trend of antimicrobials use resulting from poor consumer awareness on dangers of inappropriate use, use as a stop-gap measure, non-compliance with dosage, and self-medication as observed in Bangladesh are also common in India [69][70][71], Sri Lanka [72], Nepal [73], Pakistan [74], Indonesia [75,76], and Vietnam [77]. Due to poor level of awareness, sometimes the physicians are pressurized by the patients and/or their caregivers to prescribe antimicrobials especially in urban areas, without any proper indication. In many instances, antibiotics are used as a 'quick & cheap' alternative by both the patients/caregivers and the providers, including use for self-medication [78].
In this review, we found a large proportion of medical practitioners and students in Bangladesh unaware about the guidelines on the use of antimicrobials. The urgency of including this in the graduate curriculum cannot be overemphasized. Coupled with stringent implementation of regulatory measures in the production and distribution of antimicrobials, with appropriate incentives ('carrot and stick' approach), will go a long way in mitigating the AMR problem.

Policies and strategies are there, but implementation remains a challenge
There is no dearth of policies and strategies especially since 2014, but operationalization of these remains a challenge which is true for implementing any public policy in general in Bangladesh [79], including the SDGs [80]. Bangladesh is one of the 100 countries with National Action Plan for containment of AMR developed (as of March 2018), however, a recent review of the Action Plans identified some challenges for its implementation in LMICs like Bangladesh [81]. These include lack of functional mechanism for implementation or coordination, lack of adequate financial and institutional resources for relevant capacity and means for infection prevention and control (e.g., through WASH activities), and building awareness and political commitment. To address these challenges, measures such as mainstreaming of the AMR containment process across sectors, adequate resourcing through national budgets and annual development plans, and inter-sectoral coordination for infection prevention and control are suggested [81].

The way forward?
The importance of building awareness among the policy-makers for coordinated action across the sectors, updating medical and allied health sciences curriculum for rational use of medicines including antimicrobials, and adequate resourcing with budget and human resources cannot be overemphasized. Again, for the very fundamental task of infection prevention and control in LMICs like Bangladesh, the implementation of WASH activities has an important role to play by reducing the transmission of resistant strains in the environment [82][83][84]. This is plausible as factors such as poor sewage system; poor infection prevention and control in the hospitals, clinics, education institutions and workplaces; and poor sanitation facilities, and hygiene practices contribute to the spread of resistant strains from environment to food chain. The percentage of resistant isolates may be higher in humans compared to the environment (e.g., animal stool and water sample), but the load (number of resistant isolates/sample) is higher in environment which acts as a reservoir of resistant genes [85]. Though Bangladesh has travelled a long way in controlling open defaecation through much lauded Community Led Total Sanitation (CLTS), the environment remains highly contaminated with faecal matter [86]. In the transition, Bangladesh moved to primitive pit latrines instead of household improved latrine; 60% of the population have onsite sanitation facilities including pit latrines, but onsite sludge management is lacking. In Dhaka, 22% of the households are connected to a sewer system, but only 2% of faecal sludge is estimated to be properly treated. Though majority of the people have access to better quality water for drinking, contamination with microbes, arsenic or salts in pockets is alarming. For example, 80% of piped water is found to be contaminated with E. coli [86]. The situation is exacerbated by the absence of good hygiene practices which multiplies the effects of unsafe water and sanitation. This importance of WASH interventions is highlighted by a recent Chatam House review of the progress of the AMR situation where the author emphasized the need for more investments in WASH for sustainable containment of AMR over long run in the LMICs [87]. This should alert the policy-makers as provision of sustainable WASH services to the population has implications on overall human development (e.g., stunting, educational attainment) and long-term poverty reduction strategy in Bangladesh.
The problem of AMR is multi-sectoral, multi-disciplinary, and multi-institutional and thus need a coordinated response of the three sectors, adopting a comprehensive approach such as that of One Health. The outbreak of avian influenza in Bangladesh in 2007 exposed the vulnerability of the country to transmission of infection from animals and environment. In 2008, stakeholders in the human, animal and environmental sectors came together to promote the concept of 'One Health' in Bangladesh [88]. As a consequence of this movement, the GoB came up with the 'National One Health Strategy' in 2012 [89]. In 2016, a One Health Secretariat was established at the IEDCR with staff from three ministries (human health, animal health and environment) and support from the development partners [90]. However, improving awareness among professionals and practitioners across the sectors for consensus actions, and coordination among different sectors and ministries remain a major challenge to move forward. Given the poor state of Bangladesh to 'prevent-detect-respond' to health emergencies (i.e., outbreaks of epidemics and pandemics including AMR) as revealed by Global Health Security Index (Bangladesh occupying 113/195 position, scoring 35/100), there is little time to waste [91].

Limitations
In this scoping review of AMR situation in Bangladesh, we tried to gather maximum available information. However, due to restricted access to some of the databases, the search may not be exhaustive. Besides, there was dearth of published materials on this topic in general, and particularly in some sectors such as the contribution of environmental contamination in initiating and propagating AMR. The included articles were critically appraised but the weighted ratings were not done.

Conclusion
The factors for the development and transmission of AMR in Bangladesh are deep-rooted in various supply and demand side factors. However, irrational use of antimicrobials in, and beyond, human health sector (e.g., animal health and environment) is aggravating the situation and posing a threat to human health. To address this comprehensively, multi-sectoral and multi-stakeholder efforts are needed based on the strategy of 'One Health.' For this, critical awareness of the problem across the sectors and professionals, high level political commitment, intra and inter-ministerial coordination among relevant sectors, and enforcement of regulatory regime are urgently warranted.