Implementing Antimicrobial Stewardship in Various Healthcare Settings

Abstract

Antimicrobial resistance is a global health problem associated with mortality, morbidity, and socioeconomic losses. Given the rapid evolution of microorganisms and the scarcity of novel antimicrobials, it is important to implement strategies that promote appropriate, evidence-based use of antimicrobials to preserve their efficacy. These strategies and interventions are collectively referred to as antimicrobial stewardship (AMS). AMS interventions are focused on ensuring that the right antimicrobials are given at the right dose to the right patient, through the right route and for the right duration of time in order to improve patient outcomes, reduce side effects from inappropriate antimicrobial use and reduce the cost of therapy. AMS interventions include providing patient and public education; educating health professionals; ensuring evidence-based antimicrobial use; strengthening infection prevention and control practices; and prioritizing “one health” focused strategies to mitigate AMR in humans, animals, and the environment. Successful antimicrobial stewardship programs possess seven core elements as recommended by the CDC- leadership commitment, education of health professionals, accountability, drug expertise, action-oriented implementations, regular tracking of adherence to stewardship processes, and reporting. Stewardship interventions are successfully implemented when healthcare workers and stakeholders perceive the benefits of the program to be more than the effort required to implement the change.

1. Introduction

Antimicrobial resistance (AMR) is a global public health challenge that has continued to thrive, accounting for mortality, morbidity, and significant socioeconomic losses from prolonged illness, multiple therapies, and healthcare-associated infections. Microorganisms develop resistance to antimicrobials naturally in an effort to preserve their existence, however, antimicrobial misuse, poor infection control practices, and lack of adequate diagnostic tools have accelerated the emergence and spread of AMR [1]. AMR was the direct cause of 1.27 million deaths and played a role in 4.95 million deaths in 2019 [2]. If urgent interventions are not initiated, it could cause about $100 million in socioeconomic loss by 2050 [3].

Antibiotic stewardship (AMS) interventions are programs and strategies set up to reduce the emergence and incidence of AMR - related infections, improve antimicrobial use, and optimise patient outcomes. Antimicrobial stewardship programs ensure that the right antimicrobials are given at the right dose to the right patient, through the right route for the right duration of time [1]. These interventions are aimed at improving patient outcomes, reducing side effects from inappropriate antimicrobial use, and reducing the cost of therapy. Antimicrobial stewardship interventions should be implemented in all healthcare and non-healthcare settings including but not limited to hospitals (both in-patient and out-patient units), intensive care units, pharmacies, primary healthcare settings, nursing homes, veterinary hospitals, agricultural farms, animals houses, and in the community [1].

2. Antimicrobial stewardship interventions

To effectively implement antimicrobial stewardship interventions, you need to understand these interventions and how they can be implemented, here are some essential stewardship interventions.

2.1 Patient and public education

The general public is a major consumer of antimicrobials and should be educated on the appropriate use of antimicrobials, the administration, storage, and proper disposal of antimicrobials [4]. Awareness of AMR and its effect on morbidity, mortality, and socioeconomic impact should be explained. Information for the public should clearly address negative antimicrobial use practices observed over time and present proper alternative practices that promote proper antimicrobial use. Several studies have identified that people in many developing low- and middle-income countries (LMIC) stop using antimicrobials on feeling better, keep antibiotics at home for future use and use antibiotics based on recommendations from friends and family and this inappropriate use corresponds to the prevalence of AMR in such settings [5]. Educating the public about AMR and AMS can be done using broadcast media like television, radio, internet-based communication channels like certified websites dedicated to information on AMR and AMS, and social media. Additionally, print and multimedia materials can be made available to the public. All information materials should be presented in a simple, easy-to-understand manner, should be translated into the community’s local language(s), and should be tailored to the local cultural context in which they are used. The public should be educated on inappropriate antibiotic use for viral infections like influenza, and the wrong use of antibiotics as growth promoters in agriculture. Patients and the general public should be educated on how AMR develops and spreads, as well as interventions to stop AMR [6]. Integration of the proper use of antimicrobials into high school curricula may promote awareness and change behaviour toward antimicrobial use at an early age [1].

Likewise, direct health professional to patient education should be encouraged. All health practitioners with direct access to patients using antibiotics such as doctors, nurses, pharmacists, primary care nurses, and infection control specialists should educate patients on proper antibiotic use, and debunk myths and false information on AMR [4].

2.2 Education of health professionals

Antimicrobial stewardship intervention requires a multidisciplinary approach involving doctors, pharmacists, nurses, infection control experts, data scientists, laboratory technicians and specialists, dentists, surgeons, veterinary doctors, and primary care doctors. They should be educated on proper antibiotic prescribing and dispensing, evidence-based prescription guidelines, antimicrobial surveillance, and the importance of the “one health” approach to address antimicrobial resistance [6]. Educational modules on AMR and AMS should be included in continuing professional development (CPD) programs. In-person educational sessions have been proven to have a greater and longer-lasting effect on prescribing behaviour than printed materials [1].

Locally-adapted presentations, workshops, simulations, and lectures on AMS should be encouraged within health facilities and institutions as part of CPD. Print materials and online learning on AMS should also be encouraged. Regional health authorities should provide timely information on recent and changing trends in AMR patterns to help health facilities tailor information sessions to represent the present reality. Education on infection prevention control practices should be made compulsory to limit the occurrence and spread of healthcare-associated infection and limit patient-to-staff disease transmission and vice versa [7]. Health authorities should promote multidisciplinary teamwork among all health practitioners to ensure effective AMR reporting, surveillance, and implementation of AMS programs.

2.3 Ensuring appropriate antimicrobial use

The inappropriate use of antimicrobials, especially antibiotics has accelerated antimicrobial resistance, therefore many antimicrobial stewardship interventions focus on limiting antimicrobial use and encouraging evidence-based use when necessary [4]. Most of the several strategies to improve antimicrobial use are focused on appropriate antimicrobial prescribing and dispensing, a few are discussed below.

2.3.1 Promoting adherence to regional and/or facility-specific antimicrobial prescribing guidelines

Information from antimicrobial stewardship surveillance reports should be used to develop region and facility-specific clinical guidelines. These guidelines are to provide evidence-based prescription practices. The adherence of physicians to prescription guidelines has been found to improve the quality of care [8]. Additionally, computerised decision support systems (CDSS) can help improve adherence to prescription guidelines and provide case-specific treatment plans when needed. Technology-integrated prescription guidelines are an improved effort toward evidence-based prescription of medicines and physicians should be encouraged to embrace and utilise such innovations [8].

2.3.2 Promoting evidence-based antimicrobial prescribing

Accurate laboratory testing provides evidence for diagnosis and treatment. When available, laboratory test results help identify disease-causing pathogens which aid diagnosis. This in turn ensures optimal antimicrobial use, limits the occurrence of drug toxicity, and prevents the occurrence of subsequent antimicrobial resistance [9]. Strengthening laboratory capacity to provide prompt diagnosis and antimicrobial susceptibility test results are strategies emphasised by the World Health Organisation (WHO) to improve accurate antimicrobial prescribing [9]. The flow of samples from the patient to the laboratory and the feedback of test results should be optimised to provide timely care. The laboratory staff should periodically provide a facility cumulative antibiotic resistance report, called an “antibiogram”. This antibiogram will be used to update prescription guidelines and provide evidence-based antimicrobial treatment plan pending antimicrobial susceptibility results.

2.3.3 Reducing the prescription of broad-spectrum antibiotics

Broad-spectrum antibiotics (for example vancomycin, amikacin, and meropenem) have been proven to be effective against many species of both gram-positive and gram-negative organisms. The inappropriate use of these broad-spectrum antibiotics has been associated with the emergence of multidrug-resistant organisms [MDRO] [5, 10]. Therefore, to preserve the effectiveness of these broad-spectrum antibiotics, their prescription and use should be limited, and be determined by the approval of an infectious disease expert or consultant. Narrow-spectrum antibiotics that are only effective against a specific subset of organisms should be prescribed instead of broad-spectrum antibiotics.

2.3.4 Implementing delayed antimicrobial prescribing

This involves prescriptions issued by a doctor to a patient to be used at a later date if symptoms worsen. This intervention has been shown to reduce antibiotic use [11, 12, 13]. Within the period of delayed prescribing, non-pharmaceutical interventions can be recommended.

2.3.5 Restricting the use of antimicrobials

Restrictive antimicrobial use requires limiting the use of certain “reserve” antimicrobials (like carbapenems, vancomycin, piperacillin/tazobactam, and echinocandin antifungals) until authorised according to approved criteria. This is usually done to preserve the effectiveness of these broad-spectrum and last-line antimicrobials, and reduce the cost of therapy and potential toxicity associated with the use of these antimicrobials. These restricted antimicrobials can only be used when:

1. It has been authorised by an infection control specialist.

2. In certain indications/conditions.

3. For situations when the resistance profile of the organism warrants use.

4. When other antimicrobials are contraindicated or have failed

5. After discussion and approval with the antimicrobial stewardship team.

It is important that the use of these “reserve” antimicrobials are closely monitored, reviewed and reported. This strategy is usually implemented within a hospital, health facility, or at a regional level. An antimicrobial restriction policy and procedure document should be created to ensure compliance with restricting antimicrobial use, making it clear who is authorised to approve the use of the restricted antimicrobials and how approvals can be obtained [14, 15]. The WHO’s AWaRe categorisation alongside hospital/regional antimicrobial surveillance reports can be used to formulate antimicrobial restrictive formulary [16, 17].

2.4 Strengthen infection control practices

Infection prevention and control (IPC) strategies can be implemented at health facilities and in the community. Infection prevention programs in health facilities are mostly focused on reducing healthcare-associated infections. At the core of infection prevention practices are rapid microbial diagnosis to quickly identify multidrug-resistant organisms, and rapid intervention to curb its spread. Infection control practices are optimised when healthcare providers are well educated on the importance of these practices and their compliance are regularly monitored [18].

Infection control activities in health facilities involve regular hand washing; use of protective, sterilised gloves, masks, eye protection devices (goggles), and other personal protective equipment (aprons and gowns) when interacting with patients; appropriate disinfection of medical equipment; regular environmental cleaning and disinfection; investigating potential disease outbreak and implementing control measures; identifying and vaccinating susceptible workers against vaccine preventative diseases; appropriate infectious waste management; and the installation of high-efficiency particulate absorbing (HEPA) filters into the building’s construction to limit the spread of airborne infections.

The objective of Infection prevention and control at the community level is to minimise infection occurrence and spread between people. IPC strategies in the community focus on ensuring good hygiene and sanitation; promoting vaccination; encouraging the use of insect repellants; avoiding contact with confirmed cases of infectious diseases; practising safe sex; and ensuring appropriate use of medication [18].

2.5 Regulation of antimicrobial prescription, supply, and use

Suboptimal antimicrobial prescription practices have been linked with the emergence of resistant microorganisms, especially in LMICs [19]. Therefore, adherence to prescription guidelines and evidence-based antimicrobial prescribing based on laboratory analysis and data from antimicrobial resistance surveillance should be prioritised.

Pharmacists should ensure the continuous supply of antimicrobials and formulate a restricted antimicrobial formulary based on antimicrobial resistance patterns and the WHO’s AWaRe classification. The shortage of essential narrow-spectrum antibiotics have contributed to the increased, suboptimal use of newer and broad-spectrum antibiotics potentially promoting an increase in antimicrobial resistance [20].

All health facilities should have access to continuous supply of antimicrobials. The antimicrobial stewardship pharmacists must ensure proper selection, procurement, and distribution of antimicrobials on the prescription formularies, including the reserved antimicrobials. Pharmacists should ensure that antimicrobials are of appropriate standard and properly stored to preserve efficacy. A critical antimicrobial formulary can be developed based on infectious disease epidemiology, antimicrobial resistance patterns, and drug availability. Tools for accurate antimicrobial use projections and inventory management should be employed to prevent shortages of these essential medicines [21]. Comprehensive procurement systems and robust supply chains should be engaged to ensure that antimicrobials are readily available and affordable [22]. Regulatory authorities should discourage pharmaceutical companies from advertising antimicrobials, especially broad-spectrum antibiotics to decrease patient demand for such medicines and prevent abusive use [23].

2.6 Implementation of a “one health” approach to limit AMR

The term “One health” refers to interdisciplinary, multi-sectoral initiatives to guarantee the best possible well-being for people, animals, and the environment. Antimicrobials are rightly used in humans and animals to treat diseases, however, the prolonged use of antimicrobials for prophylaxis in humans and animals; the mass administration of antimicrobials to animals (especially antibiotics that are critical to humans like third generation cephalosporins); and the unregulated use of antibiotics (e.g colistin) at low sub-therapeutic doses as growth promoters in agriculture, have accelerated the development of antimicrobial resistance – making animals reservoirs for antimicrobial resistant organisms and antimicrobial resistant genes. These resistant organisms and genes can easily be passed into the environment when excreted in urine and faeces [24]. Antimicrobials are used in aquaculture in feeds, given as injections, and sometimes directly applied to the water to prevent or treat diseases. When the water is released into the environment, it contaminates the environment with antimicrobials [25]. Wastewater from the production of antibiotics in pharmaceutical industries can contain traces of these antibiotics and are released directly into the environment [26]. Correspondingly, the improper disposal of expired antimicrobials (of which up to 90% of the active pharmaceutical ingredient may be present) also contributes to the direct deposits of antimicrobials into the environment [27]. Farmers have also been found to use antibiotics to preserve fruits from bacterial infections, leaving them with antibiotic residues.

When antimicrobials and their metabolites are in the environment (soil, water, or air), they are mostly present at sub-therapeutic concentrations, creating selective pressure on organisms around them, resulting in these organisms becoming resistant, making the environment a reservoir of antimicrobial resistant organisms and antibiotic resistant genes. Humans interact with animals and with the environment, this interdependence creates opportunities for antimicrobial resistant organisms and antimicrobial resistant genes to be transmitted within and between humans, animals, and the environment.

It is important that wastewater and solid waste contaminated with antibiotics or their metabolites are properly treated. Wastewater and sewage sludge can be treated to remove antimicrobials and pollutants chemically by coagulation and flocculation; by adsorption using activated charcoal; by physicochemical methods – electrochemical oxidation, ozone-based antibiotic degradation, and ultraviolet rays; using membrane technology like ultrafiltration, nanofiltration, and microfiltration; biological treatments [27], liming and composting [28].

2.6.1 One health focused strategies to limit AMR

1. Farmers, veterinarians, agriculturists, aquaculturists, and all stakeholders in the food industry need to be educated on antimicrobial resistance and how improper use of antibiotics contributes to it. They should be discouraged from using antimicrobials for prophylaxis unless recommended by a veterinarian or infection control expert. They should be encouraged to apply good agricultural principles, use clean water, and observe good sanitation and hygiene to prevent infection in plants and animals. Veterinarians should be specially trained on antimicrobial stewardship practices, and encourage their clients to practice the same. Educative information on AMR may be disseminated through specific outreaches to farmers, publications in food, agro- and aqua industries, and professional development programs.

2. Countries should be encouraged to terminate the use of antimicrobials as growth promoters in line with the WHO’s recommendations [6].

3. Regional and national integrative surveillance systems should be initiated and maintained to monitor AMR trends in animals, humans, and the environment.

4. Apply relevant infection control practices to limit infections and their transfer between and within humans and animals.

3. Antimicrobial stewardship programs (ASPs)

Antimicrobial Stewardship Programs (ASPs) are consciously coordinated programs that promote the appropriate use of antimicrobials [29]. The goals of ASPs [1] are to;

1. Improve the quality of patient care and thus increase positive patient outcomes.

2. Ensure optimal antimicrobial prescribing.

3. Decrease drug-related adverse drug reactions.

4. Decrease treatment failure and mortality.

5. Reduce the transmission rate of healthcare-associated infections (HAI).

6. Reduce the occurrence of and prevent antimicrobial resistance,

7. Ensure cost-effective therapy and reduce unnecessary health costs [21].

ASP can be implemented in all settings where antimicrobials are prescribed, dispensed, or used such as hospitals, nursing homes, intensive care units, pharmacies, and primary healthcare settings.

3.1 Core elements of antimicrobial stewardship programs

All ASPs must possess certain elements that are key to the success of such interventions. These elements are a broad category of strategies needed for the success of an ASP. The Centre for Disease Control (CDC) has highlighted seven core elements of successful antimicrobial stewardship programs [29].

3.1.1 Leadership commitment

The success of any ASP relies on the support of the leadership of the health facility, regulatory institutions, pharmaceutical industries, scientists, and health insurance. Leaders support ASPs by providing adequate human resources, financial support, and information technology for the successful implementation of such programs. Executives of health organisations need to be well informed of the benefit of ASPs and their potential impact on patient outcomes. Leaders, managers, and board of directors can support ASPs by:

1. Publishing formal documents to support ASP interventions and identifying them as a top priority.

2. Incorporating stewardship-related activities in job descriptions of the antimicrobial stewardship team to afford enough time to oversee antimicrobial stewardship activities.

3. Ensuring enough time for staff from relevant departments to contribute to stewardship activities.

4. Include participation and adherence to antimicrobial stewardship guidelines or interventions in annual performance reviews.

5. Providing sustainable, sufficient, and budgeted financial support for stewardship activities such as salary, training cost and incentives, and information technology resources.

6. Support training and education of all healthcare workers involved in antimicrobial prescription and use.

7. Meet regularly with the AMS team to assess resources needed, and interventions required to overcome challenges that impede the success of ASPs [29].

Leadership at the regional and national level are also required to support ASPs to ensure multi-sectoral collaborations and formulation of regional or national action plans that align with the goals and activities of the ASP.

3.1.2 Accountability

ASPs require a leader or co-leaders, who are accountable for programs’ management and outcomes. Co-leadership of a physician and pharmacists have been shown to be effective [29]. Clinical staff are better suited to lead ASPs than non-clinical staff. These leaders must possess effective leadership, management, and communication skills.

Leaders of ASPs should have regular stewardship rounds where they interact with physicians on their choice of antimicrobials, reasons for prescriptions, and pre-authorisation of the use of restricted antimicrobials. These rounds encourage a critical review and evaluation of antimicrobial choices and assessment of physician’s adherence to prescription guidelines. Face-to-face interactions give physicians and the antimicrobial stewardship team a chance to exchange ideas in an open forum and offer real-time feedback when necessary [30]. These stewardship rounds provide an opportunity for learning and development, and can increase the confidence of physicians when prescribing antimicrobials especially when the antimicrobial stewardship team confirms their choice of antimicrobials [31], and reduce inappropriate use of broad-spectrum antimicrobials [32]. Leaders of ASPs should also provide reports of stewardship activities, interventions, and impact to the health facility and regional health leadership [33].

3.1.3 Drug expertise

Successful ASPs have a pharmacist leader or co-leader taking responsibility for appropriate antimicrobial use. Clinical pharmacists with training in antimicrobial stewardship and infectious diseases are more suitable and highly effective for this role [29]. After evaluating the patient’s diagnostic results, pharmacists can offer clinical information to support decisions regarding the patient’s antimicrobial medication regimen and length of treatment [34]. Additionally, they can help develop guidelines for the management of specific infections and particular organisms (such as multidrug-resistant Staphylococcus aureus) as well as educate health professionals on the use of evidence-based antimicrobial prescribing, and contribute to antimicrobial surveillance efforts [35].

3.1.4 Action

This involves Implementing recommended stewardship interventions like reducing the prescription of broad-spectrum antibiotics; restricting certain “reserve” antimicrobials to pre-authorisation from the antimicrobial stewardship team; and re-evaluating and assessing antimicrobial prescription 36–72 h after first administration- considering culture and antimicrobial sensitivity results, clinical scenario and patients response to therapy [33]. The reassessing of antibiotic prescription after 36–72 h after initiation is referred to as an “antibiotic timeout”, and has been associated with reduced antimicrobial use, and improved patient outcomes [36, 37, 38]. During an antibiotic timeout, changes could be made to the antibiotic selected, duration of antibiotic use, route of administration such as the transmission of intravenous antibiotics to oral antibiotics, and/or dosage such as dose optimisation in patients with organ dysfunction. Pharmacists can also raise alerts when potential antibiotic related drug–drug interactions are observed (such as interactions between fluoroquinolones and metals like calcium, iron, and aluminium- and magnesium-containing antacids), monitor patient’s drug levels, prevent unnecessary repetition of antibiotic prescriptions, and ensure antibiotics are not used beyond a reasonable time. Microbiological consultations are important for optimal antimicrobial selection and use, aseptic techniques should be employed to prevent contamination of laboratory cultures. Specific guidelines should be established to cater for infections caused by specific organisms like methicillin-resistant S. aureus (MRSA), multidrug-resistant Clostridium difficile, and specific conditions like community-acquired pneumonia [29]. Prospective audits of antimicrobial use which involves the review of antimicrobial use by an external expert is required periodically, to further improve antimicrobial use.

3.1.5 Tracking

This entails assessing the processes and outcomes of ASPs, such as adherence to prescription guidelines (process). And outcomes like a decrease in the use of broad-spectrum antibiotics, a drop in the number of antimicrobial days of therapy (DOT) per 1000 patient days, and an improvement in overall patient outcomes [29]. Additionally, antimicrobial use at a facility level, and the emergence of antimicrobial resistant diseases should be collated and monitored, and forwarded to regional and national health authorities [33]. Auditing of ASPs can help identify areas where more education or focused attention is needed, evaluate the effectiveness of AMS interventions and provide feedback on resistance patterns to regional authorities.

3.1.6 Reporting

Reports on antimicrobials prescribed, purchased, and dispensed should be made available to physicians, nurses, pharmacists, and relevant staff, along with specific action points. Information gotten from antimicrobial use audits should be shared with prescribers along with specific action points to drive compliance to guidelines. Antimicrobial resistance patterns should be evaluated and shared with the infectious disease and antimicrobial stewardship team to improve guidelines and drug formulary. Sharing reports can be used as a tool to increase compliance to prescribing guidelines and motivation to engage in antimicrobial stewardship activities. Facility-based data should also be made available to the hospital board, the ministry of health, and other regional or national health authorities to drive evidence-based interventions.

3.1.7 Education

Members of the healthcare team, including doctors, nurses, pharmacists, microbiologist, and laboratory staff should be well educated on the mechanisms and drivers of antimicrobial resistance; appropriate antimicrobial prescribing; individual roles in antimicrobial stewardship; benefits of antimicrobial stewardship; antimicrobial prescribing guidelines; antimicrobial pre-authorisation requirements; and the importance of antimicrobials stewardship intervention like antibiotic timeouts and antimicrobial use audits. Education can be done in formal and informal settings through lectures, posters, newsletters, case scenarios, educational video games, or electronic communications about antibiotic use with relevant departments [33, 39]. Education is most effective when initiated with interventions and monitored outcomes [33]. Patients should also be educated on appropriate antimicrobial use, the importance of antimicrobials, and potential side effects. Information to patients should be simple, adapted to the local language, and easy to understand.

3.2 Implementing antimicrobial stewardship programs

The first step in implementing an ASP is to form an antimicrobial stewardship committee. This committee should consist of a clinical doctor (preferably with training in infectious diseases and AMS, with keen interest in antimicrobial use and patient safety), a pharmacist (with training in infection prevention and control and antimicrobial stewardship), a nurse, a clinical microbiologist, infection control physician/expert, data analyst, information technology expert. Each member has unique roles and responsibilities.

3.2.1 Role of a physician in a stewardship team

Physicians are to develop treatment guidelines in collaboration with the infection control team and pharmacist, and also adhere to appropriate prescription practices and guidelines to ensure proper antimicrobial prescription and use. They are to ensure evidence-based decisions for infection management utilising data on antimicrobial susceptibility and laboratory diagnosis. When prescribing antimicrobials, physicians need to account for antimicrobial allergies, such as penicillin allergies, to limit adverse drug events. Physicians de-escalate the use of broad-spectrum and reserved antimicrobials to simple, narrow-spectrum regimens based on laboratory diagnosis, antimicrobial culture, and sensitivity. It is also important that they shorten the duration of antimicrobial therapy for surgical prophylaxis. In relating with patients, physicians can advise patients on appropriate antimicrobial use and how best to prevent infections. Senior physicians are to influence the prescribing of other physicians and facilitate peer-to-peer learning for improved adherence to established guidelines. Physicians are to take co-leadership of ASPs and communicate with facility leadership and stakeholders on the importance and impact of ASPs [40, 41].

3.2.2 Role of a pharmacist in a stewardship team

During antibiotic timeouts, pharmacists should assess and, if necessary, convert intravenous antibiotic regimens to oral regimens. As medicine experts, they are required to ensure the appropriate selection of antimicrobials based on laboratory test results and individualise dosing in accordance with clinical presentations, administration route, genetics, laboratory analysis, organ dysfunction, and comorbidities. Additionally, pharmacists are to collaborate with the infectious control team to develop treatment guidelines for specific infections (like community-acquired pneumonia) and specific organisms like vancomycin-resistant enterococci (VRE). Pharmacists participate in “antimicrobial timeouts” to assess the efficacy of antimicrobial prescribing practices, and “antimicrobial audits” to evaluate overall antimicrobial prescribing and dispensing practices. Based on antimicrobial susceptibility patterns, pharmacists are to create facility- and/or region-specific antibiogram to guide antimicrobial prescribing. They are also well skilled to formulate facility-based essential antimicrobial lists and restrictive formularies based on the WHO’s AWaRe classification and regional antimicrobial resistance patterns [16]; intervene and prevent drug-drug and drug-food interactions; and ensure continuous availability of essential antimicrobials [34, 35].

3.2.3 Role of nurses in a stewardship team

Nurses must ensure the aseptic collection of laboratory specimens for laboratory investigations. Laboratory specimens must be handled with aseptic techniques to prevent contamination, which could result in the use of antimicrobials where there is no medical indication for their use. They can collaborate with the pharmacist to review laboratory results to help guide antimicrobial selection. They are to administer antimicrobials promptly and record antimicrobial use. Nurses monitor patients’ progress and report signs of infection (including sepsis), allergies, and observed adverse drug events (like diarrhoea) to the physician and pharmacist. They serve as a vital communication channel between patients and doctors and assess patients’ capacity to transition from intravenous drug therapy to oral therapy [42, 43].

3.2.4 Role of microbiologist in a stewardship team

To optimise the selection and use of antimicrobials, microbiologists conduct antimicrobial sensitivity tests and interpret laboratory test results. They evaluate novel diagnostic techniques and recommend their use in healthcare settings. Diagnostic tests that are affordable, sensitive, specific, and support rapid identification of organisms and possible resistance patterns should be prioritised. They review antibiograms based on antimicrobial surveillance reports, and report cases of antimicrobial resistance throughout the healthcare system. Lastly, they educate other members of the healthcare team on standard laboratory practices for optimal antimicrobial prescribing [44].

3.2.5 Infection control specialist

These specialists are to instil infection prevention and control measures that minimise infection risk. They promote the use of personal protective equipment. They develop and implement isolation guidelines and procedures for highly infectious and critical disease cases. And ensure aseptic techniques and strategies that prevent contamination of laboratory specimens, and limit exposure of the blood and body fluids of patients. Likewise, they ensure proper waste management, environmental hygiene, disinfection, and sterilisation as well as provide education and training on proper infection prevention and control strategies to healthcare professionals [18].

3.2.6 Role of data analyst in a stewardship team

Data provides evidence for effective decision-making and should not be trivialised. Data analysts collect, validate, clean, and analyse data on the antibiotic supply, prescription, and use. They inform health facility management, regional surveillance systems, and national surveillance systems of the findings of significant data analysis. They monitor and evaluate the outcomes of ASPs in line with predetermined indicators.

3.2.7 Role of information technology expert in a stewardship team

In broad terms, information technology experts essentially digitalise systems, structures, and processes for effective storage, timely communication and intervention. They integrate electronic records into the health system to facilitate efficient data collection, and rapid sharing of necessary information, like laboratory results, among health workers and the antimicrobial stewardship team. They maintain databases of antimicrobial resistance trends, and information on antimicrobial prescribing, purchase, and use. Similarly, they promote technology-aided drug prescribing and integrate computer provider order entry [CPOE] across the health facility for multidisciplinary, holistic patient care.

3.3 Strategic action plans for implementing antimicrobial stewardship programs

ASPs are implemented in all health settings where antimicrobials are prescribed, dispensed, and used. However, there is no one size fits all approach to implementing ASPs. Below are a few essential steps in implementing ASPs, these strategies should be adopted to fit the local context of the health setting in which they are applied.

3.3.1 Create an antimicrobial stewardship committee or team

The first step is to establish the antimicrobial stewardship committee or team. The team may stand alone or be integrated into the infection control or patient safety committee. For this team to be effective, it should have the support of the leadership of the health facility, major stakeholders, and managers in the health facility. The team is to be co-led by a physician and pharmacist with training in infectious disease control, and antimicrobial stewardship. When a physician is not available, a trained pharmacist can take up the leadership role.

3.3.2 Execute a facility-based SWOT analysis

The stewardship team is to carry out a SWOT analysis of the health system to evaluate areas of strength, weaknesses, opportunities, and threats. Already existing facility or regional prescription guidelines should be reviewed, and compliance with these guidelines be evaluated. Additionally, antimicrobial use data should also be evaluated. The focus of the SWOT analysis should be on assessing the availability of the core elements of AMS at the health facility. Resources - human and capital resources needed for the program should be assessed. In cases where a specialist member of the team like a pharmacist with training in infectious disease management is not available within a facility, then another similar expert should be identified off-site within another similar facility and can be consulted to collaborate and fill that gap [45].

3.3.3 Develop a focused action plan

A well developed and planned antimicrobial stewardship intervention is needed for the success of an ASP. All core elements of antimicrobial stewardship should be well established with support from the leadership of the health facility. Senior physicians should partner with the antimicrobial stewardship team to influence other physicians to implement antimicrobial prescription and use changes that come with the ASP.

Antimicrobial stewardship activities should be identified based on facility-specific peculiarities, after a SWOT analysis has been completed. Antimicrobial stewardship programs implemented in other similar facilities can be examined and adopted to fit the local context. Action plans should focus on initiating and maintaining behavioural changes to how antimicrobials are prescribed and used. The use of antimicrobial prescription guidelines, pre-authorisation of the use of restricted antimicrobials, limiting the use of broad-spectrum antibiotics, and evidence-based antimicrobial prescriptions backed up by laboratory results should be encouraged. Pharmacists should categorise antibiotics, and restrict access to their use based on the WHO’s AWaRe classification, participate in antimicrobial use review (see Table 1) [17].

WHO Classification	Antibiotics
Access antibiotics – they possess narrow-spectrum antibiotic activity, they are affordable, safe with low resistance profile. They are usually effective against a wide range of commonly susceptible organisms. They should be used as first- or second-choice treatment option.	Amikacin	Cloxacillin
	Amoxicillin	Doxycycline
	Amoxicillin+ clavulanic acid	Gentamicin
		Metronidazole
	Ampicillin	Nitrofurantoin
	Benzathine	Procaine
	benzylpenicillin	benzylpenicillin
	Benzylpenicillin	Spectinomycin
	Cefalexin	Sulfamethoxazole+ trimethoprim
	Cefazolin
	Chloramphenicol
	Clindamycin
Watch antibiotics – they are broader-spectrum antibiotics, and are usually more expensive than the access group. They should be used in clinically critical cases or cases where the causative organisms is likely to be resistant to the access group	Azithromycin	Ciprofloxacin
	Cef ixime	Clarithromycin
	Cefotaxime	Meropenem
	Ceftazidime	Piperacillin + tazobactam
	Ceftriaxone
	Cefuroxime	Vancomycin
Reserve antibiotics – these are last-line antibiotics usually reserved to treat infections caused by multi drug resistant organisms	Ceftazidime + avibactam	Meropenem + vaborbactam
	Colistin	Plazomicin
	Fosfomycin	Polymyxin B
	Linezolid

Table 1.

WHO’s AWaRe classification of antibiotics.

SMART (specific, measurable, attainable, realistic, and time-bound) goals for the stewardship program should be set, each member of the stewardship committee should understand their roles, responsibilities, and expected outcomes, and should be supported with the necessary authorisation needed to execute their task. Indicators to measure the success of the ASP should be well defined, and a period of time to evaluate the ASP based on the set indicator should be decided on whether every 3–6 months. Feedback from each evaluation process should be considered and necessary adjustments should be made to the antimicrobial stewardship plan.

3.3.4 Initiating sustained behavioural change in antimicrobial prescription practices

For a change process to be successful, all stakeholders involved must perceive the benefits of the change to be greater than the required efforts to actualise the change, the greater the perceived benefit, the quicker the adoption. The antimicrobial stewardship team must be able to effectively communicate the reason and benefits of changes in antimicrobial prescribing practices, and other stewardship activities to clinicians and stakeholders. Physicians must understand the proposed benefits of antimicrobial stewardship practices to the patients and also to them. The team must take into account factors that influence wrong prescribing practices and work on addressing them. It is important that all stakeholders are consulted on the ASP and the changes that will be initiated. Having informal focus group discussions will help the stewardship team take into account the views of other health actors and limit potential resistance to stewardship programs when initiated and scaled up [45].

Behavioural changes and interventions initiated by the stewardship program will be speedily adopted and scaled up if they possess the seven CORRECT attributes.

1. Credible: Stewardship interventions should be evidence-based and should be supported by respected staff (like consultants and senior physicians) and leadership of the health facility.

2. Observable: There must be established evidence and testimonials that suggested interventions have yielded measurable success in similar settings. Study tours or site visits to such facilities with successful stewardship programs are encouraged so adopters see for themselves the benefits of such interventions.

3. Relevant: stewardship interventions must be adopted to solve established challenges in the local setting to which they are applied, making them relevant.

4. Relative advantage: The suggested interventions should present relative advantages over existing practices to the patient and health professional. Health facility leadership/management may further support interventions that manage human and financial resources better, and save cost. Additionally, the perceived benefit of the intervention must be greater than the perceived effort and time required to implement the intervention.

5. Easy: Interventions should be presented in an easy-to-understand and implement, simplified manner while preserving its essential components.

6. Compatibility: Stewardship interventions should align with the basic core values of the health setting in which they are initiated. Examine ways to implement stewardship interventions using already existing systems to limit excessive changes. Also, adopt stewardship interventions to the local context to address facility-based challenges.

7. Testable: Stewardship interventions should be testable on a small scale, maybe in a unit of the hospital before it is implemented on a large scale. This provides an opportunity to identify loopholes in the implementation plan and make necessary changes, potentially increasing the program’s likelihood of success on a larger scale.

When stewardship interventions possess these attributes, they are easily embraced and are less likely to face rigid opposition when implemented.

3.3.5 Identify change agents/stewardship champions

To effectively initiate long-lasting change, local change agents are required. These change agents (antimicrobial stewardship champions) are early adopters of the changes initiated by the AMS team. These champions lead others to adopt new practices, and transmit their commitment and enthusiasm. These champions are often well respected and have the credibility and capacity to influence others. A change agent could be a senior manager or consultant clinician working to drive the implementation of, and adherence to stewardship principles among physicians in a health facility. Change agents should be able to effectively navigate the cultural, individual, and social differences among staff that may limit the success of the ASP. They should be equipped with knowledge of antimicrobial stewardship practices and leadership skills to sustain change.

The activities of these change agents should receive positive reinforcement and support from the antimicrobial stewardship team and health facility leadership, they should be acknowledged and appreciated. These agents can also be channels of feedback on the progress of the ASP.

3.3.6 Provide a favourable environment for change

All health workers must be educated on antimicrobial stewardship practices and their benefits to them and the patients. Education can be done using clinical case studies, lectures, and e-learning materials. This can be integrated into staff mandatory development programs. When possible, a trip to another health facility where ASPs are in full effect is encouraged. Through site visits and study tours, they see for themselves changes to expect through an ASP and the real-life benefits to the patients and health practitioners. The stewardship team and health leadership should clearly state the roles and responsibilities of the different departments and staff involved in the ASP. Leadership should provide the resources and support necessary to effectively execute these tasks.

ASP requires multidisciplinary collaborations, thus, structural and organisational changes and strategies should be established to promote quick communication; encourage feedback and open discussion on challenges or important issues that arise during the programs; and advance partnership across departments.

Change agents and the AS team should work to provide continuous encouragement and technical assurance to staff that are involved in the day-to-day activities of the AS processes. Health leadership must positively enforce their commitment to change processes initiated by the AS team. Their attitudes and statement should clearly communicate “This change is necessary, and we support it”.

It’s commonly said that “perfect is the enemy of good”, it is important that ASPs are initiated as soon as possible and are not delayed till when the situation is “perfect”.

3.3.7 Monitor and evaluate stewardship programs

Adherence to stewardship interventions should be monitored and evaluated periodically. ASP can be evaluated by the stewardship team every 3–6 months (or at a frequency agreed upon by the stewardship team), and the impact can be shared with stakeholders to further obtain their support and approval of the program. Results should also be discussed with the health workforce and various departments, to provide possible solutions to challenges encountered while initiating the stewardship interventions.

Antimicrobial prescription and antimicrobial use audits should be initiated regularly, antibiograms and drug formularies should be updated regularly based on data from antimicrobial resistance and susceptibility surveillance. Monitoring and evaluation practices provide an opportunity to obtain feedback from clinicians and stakeholders on ASP, address challenges and encourage further compliance with stewardship interventions. SMART goals and indicators agreed on at the beginning of the intervention process will be valuable during monitoring and evaluation. Information regarding the success of ASP, and patterns of antimicrobial susceptibility can be shared with regional and national surveillance teams and health authorities.

3.3.8 Implement feedback

Important information gotten from the monitoring and evaluation process, and antibiotic audits should be shared with the health professionals and leadership and should be implemented. Identified challenges should be discussed and practical solutions should be initiated.

4. Conclusion

The problem of antimicrobial resistance possesses a global threat to health, finance, and food security, and although only a few “new” antimicrobials have been developed over the years, a combination of effective strategies have been identified to mitigate this global public health challenge. Antimicrobial stewardship programs targeted at implementing evidence-based antimicrobial use, restricting the use of “broad-spectrum” and “reserve” antimicrobials, limiting the occurrence of AMR-related infections, and promoting infection prevention and control practices should be implemented in all settings where antimicrobials are prescribed and used. A “One health” approach to tackle AMR should be prioritised considering the interaction and interdependence between and among humans, animals, and the environment. Stewardship interventions have been proven to be effective in improving antimicrobial use and patient outcomes, and are readily accepted and implemented when they are presented to be beneficial to the health practitioner and the patient; made easy to understand and implement; and unequivocally supported by health leadership and important stakeholders.

5. Additional resources

5.1 ASP in the hospital

• Vieceli T, Rello J. Optimisation of antimicrobial prescription in the hospital. European Journal of Internal Medicine. 2022. https://doi.org/10.1016/j.ejim.2022.08.035.

• Mendelson M, Morris AM, Thursky K, Pulcini C. How to start an antimicrobial stewardship program in a hospital. Clinical Microbiology and Infection. 2020;26(4):447–453. https://doi.org/10.1016/j.cmi.2019.08.007.

• Cheong HS, Park KH, Kim HB, Kim SW, Kim B, Moon C, Lee MS, Yoon YK, Jeong SJ, Kim YC, Eun BW. Core elements for implementing antimicrobial stewardship programs in Korean General Hospitals. Infectious Chemotherapy. 2022;54(4). doi: 10.3947/ic.2022.0171.

• Doron S, Davidson LE. Antimicrobial stewardship. Mayo Clinic Proceedings. 2011;86(11):1113–1123. https://doi.org/10.4065/mcp.2011.0358.

5.2 ASP in the ICU

• Chiotos K, Tamma PD, Gerber JS. Antibiotic stewardship in the intensive care unit: Challenges and opportunities. Infectious Control Hospital Epidemiology. 2019;40(6):693–698. doi: 10.1017/ice.2019.74.

• Murphy CV, Reed EE, Herman DD, Magrum B, Beatty JJ, Stevenson KB. Antimicrobial Stewardship in the ICU. Seminars in Respiratory Critical Care Medicine. 2022;43(1):131–140. doi: 10.1055/s-0041-1,740,977.

• Pickens CI, Wunderink RG. Principles and Practice of Antibiotic Stewardship in the ICU. Chest. 2019;156(1):163–171. doi: 10.1016/j.chest.2019.01.013.

5.3 ASP in nursing homes

• Crnich CJ, Jump R, Trautner B, Sloane PD, Mody L. Optimising antibiotic stewardship in nursing homes: A narrative review and recommendations for improvement. Drugs Ageing. 2015;32(9):699–716. doi: 10.1007/s40266-015-0292-7.

• McElligott M, Welham G, Pop-Vicas A, Taylor L, Crnich CJ. Antibiotic stewardship in nursing facilities. Infectious Disease in Clinical North America. 2017;31(4):619–638. doi: 10.1016/j.idc.2017.07.008.