FormalPara Key Summary Points

Rapid diagnostic test (RDT) utilisation in antimicrobial stewardship programmes (ASPs) is variable across low-to-middle income and high-income countries.

The 5P (programme support, preserve, practicable, population health, and precision) Value Framework is proposed to enable a wider analysis of the value of RDTs in an ASP beyond per-patient outcome measures.

Effective implementation across a range of resourcing, communication, education, logistic, and interfacing activities is key to maximise RDT adoption.

Experts advocate the inclusion of RDTs in the World Health Organization Model List of essential in vitro diagnostics and in iterative development of national action plans.

Introduction

Infectious disease rapid diagnostic tests (RDTs) are fast and accurate medical tests used to identify infectious organisms and evaluate antimicrobial susceptibility [1]. RDTs are one of the most important tools the global community can use to preserve the value of antimicrobials [2, 3]. Generally, RDTs are undervalued, as their utility is viewed by their per-patient impact, rather than by the wider societal benefit of faster diagnosis and reduction in onward transmission of communicable diseases [4, 5]. In some way, the coronavirus disease 2019 pandemic has highlighted the global societal value of RDTs and raised awareness of the importance of diagnostic capabilities [6,7,8]. However, global use of RDTs as part of antimicrobial stewardship programmes (ASPs) remains low [9, 10].

Implementation and use of RDTs in ASPs is associated with multiple clinical benefits; similarly, ASPs play an important role in the effective implementation of RDTs [11]. Thus, ASPs must evolve alongside technological advancements of RDTs and be continually re-evaluated [12]. Goal 3 of the national action plan (NAP) for combating antibiotic-resistant bacteria in the USA calls for the development and use of rapid and innovative diagnostic tests for identification and characterisation of resistant bacteria [13]. Despite increasing recognition and emphasis of the importance of RDTs to ASPs, other NAPs do not include mandates to implement RDTs in ASPs. For example, the NAP for antimicrobial stewardship (AMS) in the UK acknowledges the need for RDTs but does not provide specific recommendations for their use [14].

Whilst the value of novel antimicrobials has recently begun to be reconsidered by recognising wider clinical, societal, and economic impacts [15], similar perspectives on valuing infectious disease RDTs are not as well developed. In this paper, the value of RDTs as part of an ASP, beyond per-patient clinical and cost outcomes, is triangulated through an expert working group (EWG) and synthesis of published literature. The reasons behind the potential underuse of RDTs in ASPs across low-to-middle income countries (LMICs) and high-income countries (HICs) are also explored.

Methods

A panel of seven experienced infectious disease physicians, translational pharmacists, academics, and microbiologists from Colombia, Japan, Nigeria, Thailand, the UK, and the USA was identified using a stratified snowball recruitment method. Snowball recruitment is a sampling method where one interviewee provides the name of at least one more potential interviewee. The subsequent interviewee then provides the name of at least one more potential interviewee, and so on [16]. Purposeful selection was used to establish an EWG with representation across low-to-middle and high-income resource settings as well as different global regions. Three experts represented LMICs, including Colombia, Nigeria, and Thailand, and four experts represented HICs including Japan, the UK (two experts), and the USA. Country income levels correspond to classifications determined by the World Bank [17].

A mixed-methods approach was used to capture experiential knowledge from the EWG as well as from published literature. During semi-structured one-on-one interviews, from 26 May 2022 to 12 August 2022, experts provided ‘on-the-ground’ opinions gained from implementing RDTs, treating patients with suspected infectious disease, and managing ASPs. Experts also guided the search strategy required for a targeted literature review (TLR) to evaluate the clinical and economic outcomes associated with RDT use as part of ASPs.

PubMed was searched from 24 June 2010 to 24 June 2022 using the search terms described in the ‘Search Strategy and Selection Criteria’ section (Table S1 in the supplementary material). Articles were reviewed using predefined inclusion and exclusion criteria (Table S2 in the supplementary material). Screening stages were conducted by a single expert reviewer, with a 10% check conducted by a second reviewer. Of note, articles were excluded if they did not present data in the context of an ASP or an AMS initiative, such as infectious disease physician support alone. The quality of evidence for outcomes selected for inclusion in this TLR was considered and is described in further detail in the supplementary material.

Results from the literature review were discussed by the EWG during a meeting on 9 September 2022, together with considerations for RDT implementation across a range of hospital settings and global regions. A meeting on 20 October 2022 validated the recommendations in this paper.

Compliance with Ethics Guidelines

This review does not contain any new data with human participants or animals performed by any of the authors.

Search Strategy and Selection Criteria

A combination of keywords was used: (“antimicrobial stewardship” OR “antimicrobial program*” OR stewardship OR program*) AND (“point-of-care testing” OR “rapid diagnostic test” OR “rapid diagnostic” OR “rapid test” OR “rapid antigen” OR “rapid assay” OR RDT); NOT (“immunisation program*” OR “immunization program*”). Non-human study participants and non-English literature were excluded. Grey literature searches were conducted using keyword website searching, including the European Congress of Clinical Microbiology & Infectious Diseases, IDWeek, American Society for Microbiology Microbe, and national Health Technology Assessment sites.

Results and Discussion

To explore the value and impact of RDTs within an ASP, one must first consider the global definition of an RDT. The EWG agreed that a wide range of definitions exist for ‘rapid’, varying from 90 min up to 24 h. According to a Delphi Consensus in Asia–Pacific, RDTs should provide results within 4–6 h to determine treatment before administration of the second dose of an antimicrobial [18]. To accommodate a variety of settings, where this is not possible delivery of results within 24 h may be acceptable [2].

“If we can do [an RDT] from a positive blood culture, get an answer from there in an hour or two, that’s a day or two ahead of conventional microbiology… that’s rapid.”

Clinical Pharmacist in Infectious Diseases, USA

“Whenever you’re thinking around the word rapid, you’ve got to add on front time for transport and back time for result generation onto an IT platform and transmission back to where it can be actioned.”

Clinical Fellow in Infectious Diseases, UK

Members of the EWG from HICs noted that some non-molecular tests such as matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) and VITEK®2 may not be regarded as RDTs in some settings, since HICs have access to molecular RDTs that give results within several hours. Whilst ‘rapidity’ is important, the accuracy, performance, and information provided by the diagnostic test are equally vital characteristics. Moreover, although molecular RDTs add granularity to microorganism identification, they are not used in isolation, and further diagnostic tests are usually needed for phenotypic characterisation to guide antimicrobial prescription. Therefore, a global definition of RDT needs to encompass a multitude of RDT modalities, ever-improving turnaround times, and where the test is conducted [9].

The EWG proposes the following global definition of RDTs for use in ASPs: Infectious disease RDTs include both microbial and host assays which can be conducted and actioned within a 24 h period that can substantially support ASPs.

Whilst some regions may not consider biomarkers as RDTs, the EWG agreed that biomarkers of infection are key to both antimicrobial initiation and cessation decision nodes when turnaround time is appropriate. Biomarkers of infection, including C-reactive protein, erythrocyte sedimentation rate, and procalcitonin, help to determine host response and stratify risk of patients with infection. In some LMIC settings, use of RDTs is limited to evaluation of biomarkers.

Why is the Global Use of RDTs Low?

The EWG agreed that global use of RDTs in infection-related management strategies could be increased, particularly the use of molecular RDTs in Africa and the Asia–Pacific region. The EWG outlined several barriers to RDT use across HICs and LMICs (Fig. 1).

Fig. 1
figure 1

Main barriers to use of RDTs, derived from EWG semi-structured interviews. EWG expert working group, RDT rapid diagnostic test

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Although some biomarkers like procalcitonin and C-reactive protein are included in the World Health Organization (WHO) Model List of essential in vitro diagnostics (EDLs), they are not mandated for use [19]. The LMIC representatives of the EWG advocated for the inclusion of non-molecular RDTs and other biomarkers in the WHO Model List of EDLs [19]. Furthermore, insufficient quality of evidence has resulted in a general lack of guidance from professional societies and guidelines. For example, the updated Infectious Diseases Society of America guidelines for AMS make a weak recommendation for ASPs to advocate RDTs for bloodstream infections (BSIs) as a result of moderate-quality evidence [20]. Additionally, RDTs are perceived as expensive compared to non-rapid laboratory-based diagnostic assays [21].

“In our day-to-day practice, it’s almost exclusively culture based for the majority of infections.”

Infectious Diseases Physician and Clinical Microbiologist, UK

“Right now, most of the RDTs need to be confirmed by conventional methods, which means additional time and costs.”

Professor of Infectious Diseases, Japan

Providers tend to prioritise antimicrobial prescriptions over diagnostic testing, and such prescribing behaviours can be entrenched and resistant to change [22]. Generally, RDTs are complementary to conventional culture-based methods [23, 24]. RDTs help provide information more quickly and allow changes to be made sooner but do not yet replace traditional culture-based methods which are considered the ‘gold standard’ for detection of many infectious pathogens and crucial for determining antimicrobial susceptibility. Using both techniques requires more human resources and incurs additional costs.

“Due to the National Insurance programme [in Thailand], patients pay $1 and can be admitted to hospital for any treatment]; in that situation, the hospital tries to limit tests.”

Professor and Chief of Infectious Diseases, Thailand

“The system we have [in Japan] where AMS activities are reimbursed is fairly unique. The national insurance pays us a fixed amount per patient to do AMS and we use that money to run the programmes. There is the possibility to pay for some [RDTs] out of this of funding. This could be a model for steady support for activities and testing [elsewhere].”

Professor of Infectious Diseases, Japan

“Patients pay out of pocket for healthcare [in Nigeria]. Cost affects availability. Clinicians tend to think that the patient needs to buy the drugs first… How do you know this [patient] needs this antibiotic? It’s a behaviour that will need to change...”

Associate Professor, Nigeria

Reimbursement models differ significantly in each country, and these policies impact RDT use. Although overall costs are typically higher for molecular RDTs than for non-molecular RDTs, in 2020, state-based government insurance reimbursement rates for a molecular RDT were higher than for a non-molecular RDT in Georgia, USA [25]. The additional cost of molecular testing may be offset by lower costs associated with appropriate prescribing and decreased time of performing cultures [25]. However, such cost savings are not commonly redirected to the laboratory that initially invested capital to purchase the RDT, resulting in disconnected cost silos.

What Value Do RDTs Bring to AMS?

The value of RDTs was explored via the TLR and discussed by the EWG. The following results summarise the data identified from the TLR. The searches retrieved 1829 articles and conference abstracts. Of these, 69 reported clinical and economic outcome data recorded in hospital or long-term care facility patients with suspected infection tested with any RDT as part of an ASP or an AMS initiative. Full details are shown in Fig. S1 in the supplementary material. Most data were from retrospective and observational studies (n = 39) and randomised controlled trials (RCTs) were scarce (n = 4) (Fig. S2 in the supplementary material). There was a gap in globally representative data, with most published research focused on the USA. Additionally, almost all studies reported RDT use for suspected BSIs. The overall quality of the evidence for outcomes selected for inclusion in this review was rated low using an objective assessment (see Tables S4–S7 in the supplementary material).

Reduced Mortality

Many studies identified in the TLR reported infection-related and all-cause mortality across a variety of time points including 7-, 15-, 28-, 30-, and 60-day mortality. Of these, four quasi-experimental studies and two retrospective studies demonstrated that RDTs plus ASPs were associated with improved all-cause 30-day mortality compared with conventional or standard-of-care interventions [26,27,28,29,30,31]. For example, MALDI-TOF combined with antimicrobial susceptibility testing (AST) intervention significantly decreased time to organism identification and was associated with a significant reduction in 30-day all-cause mortality (12.7% vs. 20.3%, p = 0.021), when retrospectively compared to conventional identification methods [27]. However, two RCTs and three quasi-experimental studies did not demonstrate an additional benefit of RDT use on 30-day mortality [32,33,34,35,36].

Improved AMS Metrics

AMS metrics may be indirectly positive for patients but not directly associated with clinical (morbidity or mortality) impact; outcomes related to AMS were highly variable across the literature review. Overall, studies demonstrated a reduction in time to optimal therapy [27, 29, 37,38,39,40,41,42,43,44] and time to effective therapy following an RDT plus an ASP [27, 37, 40,41,42,43,44].

Five studies (one RCT [33], three retrospective studies [38, 45, 46], and one quasi-experimental study [47]) demonstrated significant reductions in time to de-escalation following RDT plus ASP intervention when compared to conventional diagnostic methods. Only three studies (one RCT [33] and two retrospective studies [38, 46]) demonstrated significant reductions in time to escalation following RDT plus ASP intervention. One quasi-experimental study [34] and one retrospective study [45] demonstrated a numerical reduction in time to escalation following RDT plus ASP, and both state that ASP intervention was only performed on weekdays.

Decreased Length of Stay

Twelve studies identified in the TLR showed that RDTs combined with ASPs were associated with significant decreases in hospitalisation and/or intensive care unit (ICU) length of stay (LOS) [27, 28, 35, 40, 42, 43, 46, 48,49,50,51,52]. In a retrospective study, use of Gram-negative blood culture test (BC-GN) plus an active ASP intervention was associated with a significant decrease in hospital LOS (7 vs. 9 days [interquartile range 5–15 vs. 4.5–21], p = 0.001), when compared to the preintervention group [46]. LOS was the most common economic outcome identified in the targeted literature review; however, despite a general trend towards reduced LOS after RDT intervention in ASPs, most findings were not significant. This may be due to factors such as study design, e.g. an underpowered study; only looking at intensive care units where infection may not be the only issue governing LOS; or inappropriate population selection.

Other commonly reported economic outcomes included internal hospital costs and hospital readmission rates. Although economic outcomes were reported across most studies identified, only two were economic models [24, 53]. Most data and methodology utilised could not demonstrate a direct economic benefit of RDT use, which may be due to the study design, e.g. if ASP metrics were not included as primary outcomes. Whilst some savings can be made by reducing antibiotic use, it was noted that RDTs are expensive to implement and use as an adjunct.

Cost-Effectiveness

In a cost-effectiveness analysis of competing strategies for the diagnosis of BSI alone or combined with an ASP, molecular RDTs were determined to be cost-effective for the diagnosis of patients with suspected BSI [24]. The economic model compared the cost-effectiveness of different strategies used for the identification of bacterial organisms and/or the presence of antibiotic resistance among these patients. MALDI-TOF plus an ASP was the most cost-effective strategy, resulting in savings of $29,205 per quality-adjusted life year (QALY) and preventing one death per 14 patients with suspected BSI, compared to conventional laboratory methods without an ASP (incremental cost-effectiveness ratio [ICER], − $29,205/QALY) [24]. Other cost-effective options included BC-GN plus an ASP (ICER, − $23,587/QALY) and polymerase chain reaction plus an ASP (ICER, − $19,833/QALY); RDT alone without ASP was not cost-effective [24].

Another study assessed the cost-effectiveness of treating malaria based on microscopy, RDT, or presumptive diagnosis as part of a malaria control programme in Uganda. Malaria RDTs (primarily histidine-rich protein II-based tests) were conducted in healthcare centres with no laboratory infrastructure [53]. Overall, malaria RDTs were the most cost-effective with the lowest ICER (US $5.0), compared to microscopy (US $9.61 per case correctly diagnosed and treated) [53]. Malaria RDTs were cost-effective in both low- and high-transmission settings [53].

The EWG noted that economic analyses are important and must consider the broader ASP in the local area. Cost benefits of RDT use are difficult to translate across settings, and most available economic evidence is not applicable to LMICs.

Nine studies identified in the TLR suggest that RDTs plus ASPs are associated with reduced hospital costs [30, 42, 43, 54,55,56,57,58]. One study evaluated total hospital costs following MALDI-TOF implementation and dedicated pharmacy stewardship personnel time [30]. Data used in the cost analysis were derived from patients; and factors considered included the cost of RDT implementation, the cost of pharmacist and microbiology technologist time, laboratory costs, and costs associated with LOS. As a result of MALDI-TOF implementation and ASP pharmacy stewardship, total hospital costs decreased by $2439 per BSI, giving an approximate annual cost saving of $2.34 million [30].

Overall, most studies in the TLR indicated that RDTs have a positive impact on AMS metrics, but not on clinical outcomes such as mortality. A wide variety of AMS metrics were reported, including time to optimal therapy, time to effective therapy, time to escalation, and time to de-escalation. Future studies, including RCTs, with more rigorous designs (e.g. higher statistical power, or with primary outcomes focused on key AMS metrics and clinical outcomes) are needed to better capture the impact and evaluate the value of RDTs in ASPs. Demonstrating outcomes not only at the individual level but also at the population level requires studies developed in collaboration with many stakeholder organisations, clinical and physician societies, and government groups [5].

Value Benefits of RDT Use in ASPs

Reflecting the themes derived above, to define the value of RDT use, the EWG proposed five aspects of value benefits of RDT use in an ASP, as part of the 5P (programme support, preserve, practicable, population health, and precision) framework (Table 1). The value framework for RDTs was modelled on the STEDI (spectrum, transmission, enablement, diversity, and insurance) principles, which were used as the evaluation framework for the de-linkage pilot in England, and re-valued infection therapies [59, 60]. The proposed 5P framework will allow future wider analysis of the value of RDTs in an ASP beyond per-patient outcome measures.

Table 1 5P framework: value benefits of RDT use in an ASP
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Across both HICs and LMICs, the EWG agreed that RDTs bring value to ASPs and aid in the fight against antimicrobial resistance and clinically challenging pathogens. Even where RDTs are not widely available, there is value seen in diagnostics in general as they aid surveillance and provide epidemiological data [61]. Beyond the clinical and economic value described in the literature, the EWG recognised a broader impact and value of RDT use in ASPs to a variety of stakeholders including hospitals, clinicians, patients, and wider society (Fig. 2).

Fig. 2
figure 2

The value of RDT use in ASPs to key stakeholders: hospitals, clinicians, patients, and society. AMS antimicrobial stewardship, ASP antimicrobial stewardship programme, RDT rapid diagnostic test

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Effective Implementation is Key to Realise the Value of RDTs in ASPs

In this section, opinions from the EWG were combined with supporting data from the literature.

“We have all these very nice gadgets and tools which we can implement. But we’ve learned from our experience in terms of trying to develop and implement technology that you can’t force these into someone’s decision-making pathway. They must be developed and designed to fit in with current processes in a way that isn’t burdensome on the end user.”

Clinical Fellow in Infectious Diseases, UK

To achieve optimal antimicrobial use, RDTs must be used to facilitate decision-making at various stages of the clinical pathway, i.e. antimicrobial initiation, on-treatment, and de-escalation [18 ]. Use of RDTs as part of bundled interventions that support decision-making is key. Generally, experts acknowledge molecular RDTs to be most valuable in the initiation phase of the patient care pathway (Fig. 3). Early, safe de-escalation of antimicrobials based on RDT results can also play an important role in ASPs by reducing antimicrobial consumption [34, 38, 45,46,47].

“[RDTs] bring a lot of clinical benefits of course because they can make a quick diagnosis, especially in the ICU. It’s very important to start with the right antibiotic, the right one will decrease mortality.”

Scientific Advisor, Colombia

Fig. 3
figure 3

EWG perspectives on RDT use across the patient care pathway. EWG expert working group, HCP healthcare professional, RDT rapid diagnostic test

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Implementation requires more than the provision of the test: it requires support and training, ensuring the test fits within the clinical decision-making pathway and ASP, and the provision of available resources including staff and laboratory capabilities. Successful implementation in both LMICs and HICs is dependent on five main aspects: communication, resources, justification, education, and behaviour.

Communication

Alongside physicians and pharmacists trained in infectious disease, the EWG recognised the importance of the microbiology laboratory and information technology staff in the implementation of RDTs within ASPs. Close communication between the laboratory and the ASP team results in savings which can offset the added RDT cost [51].

“If you implement an RDT [but] don’t have the support staff from stewardship to do the active intervention, and [call] providers and translate outputs, you might as well not even have [that RDT]. That’s where a lot of people struggle even if they can afford to bring in the test.”

Clinical Pharmacist in Infectious Diseases, USA

Resources and Justification

The EWG reinforced that each region is affected by different economic development levels and infrastructure and therefore RDT implementation is specific to each setting. When considering resources, this should be based on prioritisation of areas of greatest ASP impact or improvement within that setting. Achieving this requires effective utilisation of hospital and laboratory data to help prioritise ASP goals.

“Our intensive care colleagues are really interested in these types of tools and there is a willingness to engage with them. It becomes a business case [to] demonstrate the benefit.”

Infectious Diseases Physician and Clinical Microbiologist, UK

“Studies of cost-effectiveness [are needed] to try to show the administrators how important [RDTs] are [alongside] the ASP.”

Scientific Advisor, Colombia

At the national level, country-specific economic models can help to justify and guide decision-making processes regarding RDT use. For example, a cost-effectiveness analysis conducted from a Brazilian Public Health System perspective, used data on direct medical costs to evaluate molecular RDTs to diagnose methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Gram-negative bacteria (CRGNB), and vancomycin-resistant Enterococcus spp. (VRE) [62]. Although the model did not evaluate RDT use as part of ASPs, complementary use of molecular RDTs and conventional methods were shown to be more cost-effective than conventional methods alone for the detection of antimicrobial drug-resistant bacteria in BSI [62].

Education and Behaviour

More education and training of clinical teams outside infectious disease specialties is needed to increase awareness and optimal use of RDTs.

“Awareness should be driven among clinicians to know that [RDTs] are available. A lot of doctors were taught in medical school about biomarkers. They’ve never seen them. Their labs don’t have them, so they don’t request them, and they’ve forgotten about them.”

Associate Professor, Nigeria

“I would say that education is key. Some [hospitals] have [RDTs], but [clinicians] try not to use them very often. Many physicians don’t know how to use them.”

Scientific Advisor, Colombia

“There is no expertise to help with the interpretation of the results with some diagnostics.”

Professor and Chief of Infectious Diseases, Thailand

Diagnostic stewardship must be incorporated in ASPs to guide the use of RDTs in the patient pathway and to support interpretation of RDT results. ASP-supported interpretation of RDT results helps expediate antimicrobial therapy optimisation and decrease broad-spectrum antimicrobial use for several organisms. Some studies indicate that procalcitonin guidance can reduce duration of treatment and daily defined dose (DDD) and is associated with significant decreases in mortality [63, 64].

RDT Selection and Implementation

Here, the EWG outline approaches for RDT selection and implementation in ASPs. When deciding which RDTs should be implemented, ASP teams should consider the prevalent or problematic organisms within their hospital setting, as well the sensitivity and specificity of each test [23]. The EWG compiled a checklist to facilitate hospital RDT implementation in any hospital setting and geographical region (Table S3 in the supplementary material). Experts agreed on the imporance of considering existing interventions and processes that the candidate RDT can complement. Microbiologist-validated RDT instruments should be used, and laboratory staff should guide discussions on implementation of RDTs and new AST interpretive criteria [23, 65]. Test location, i.e. at point of care versus in the laboratory, impacts the governance of test use as well as internal and external quality assurance. Ultimately, this determines who runs the test, who pays for the test, and who oversees the quality assurance of the test [25].

The ASP team and microbiology laboratory must elucidate RDT processes within local protocols and algorithms, detailing what RDT to perform, where to send specimens, and how to respond to RDT results [25, 43]. Thus, total process efficiency is key to effective implementation. This includes end-to-end efficiency from the moment a test is ordered, through to specimen collection, testing in the lab, and communication of the result outside the lab that will impact or change patient care. If a hospital is expecting value from an RDT, the hospital must make sure there is nothing that negates that value in the workflow, such as process inefficiencies. To aid RDT selection in any hospital setting and geographical region, the EWG summarised the main implementation factors for each RDT, ordered by lowest to highest sophistication (Table 2).

Table 2 RDT selection and implementation factors
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The EWG agreed that robust RDT post-implementation follow-up processes are required to ensure adoption upon implementation. ASPs must document clinical and economic outcomes associated with each RDT and consequent impact on patient care [36, 65]; the 5P approach enables a whole-healthcare economy lens through which to make these evaluations. Hospitals and long-term healthcare facilities must establish key performance indicators (KPIs) to measure RDT effectiveness [18].

“It is important to tailor [KPIs] to what you can accomplish [in your setting]. For example, maybe you have overuse of vancomycin [in your setting] and that’s your main target. [This] makes data a little easier to collect.”

Clinical Pharmacist in Infectious Diseases, USA

Most hospitals focus on easily accessible pharmacy metrics, i.e. DDD, concordance with policy, concordance with AST results, and time to effective antimicrobial therapy. However, these KPIs can be harder to extract in some settings and the most appropriate KPI for each ASP is dependent on the capabilities on the resources of the setting. In hospitals with minimal ASPs, a focus for the laboratory could be turnaround time, whereas a setting with advanced ASP may be able to focus on hospital level outcomes and data collated for LOS and mortality. Moreover, KPIs must reflect effectiveness of RDTs against local data [18, 69]. The combination of passive guidance through evidence-based institutional guidelines, active monitoring, and feedback of prescribing patterns by ASP teams, as well as real-time data, can improve local antimicrobial management [47].

Future Directions

The EWG discussed that, to realise the true impact of RDTs on ASPs, there needs to be investment in appropriately designed studies (e.g. ASP metrics as primary outcomes) which are adequately powered to evaluate this impact. The EWG have identified the following areas for focus: more robust clinical studies in a range of non-academic or community-based settings; larger studies that capture representative patients; targeted cost-effectiveness studies in a range of geographical locations; and studies to investigate the value of RDTs to ASPs and wider society.

Limitations and Strengths

This work has some limitations. Firstly, the EWG was represented by one expert per country across selected HICs and LMICs (except for the UK which was represented by two experts). Although the EWG was recruited from a variety of geographical regions, within each region there remains a high degree of intercountry variability. Therefore, the views expressed in the EWG may not be representative of all possible issues around RDT use in ASPs in each country. Secondly, snowball recruitment for selecting group members may risk exclusion of experts with alternative views. This was mitigated by one-on-one interviews that enabled group members to provide independent opinions before validating a consensus during EWG meetings. Thirdly, the targeted literature review results are based on a single database (PubMed) and were developed to capture articles reporting clinical or economic data covering RDT use within an ASP, and therefore studies without programmes or AMS initiatives were not included. In addition, the majority of the literature identified in the TLR is based on evidence in HICs, which has implications for the applicability of findings to LMICs. The EWG are aware that additional studies exist investigating biomarkers as RDTs; however, biomarkers are often not identified as RDTs within the literature. All literature was limited to English language, thus excluding literature from non-English speaking regions.

Conclusion

Experts across HICs and LMICs agree that RDTs have significant potential to bring substantial value to patients, clinicians, ASPs, healthcare providers, and wider society. However, supporting published evidence, at least for perspectives beyond just the per-patient impact, remains sparse. Results from this review indicate that published evidence for the clinical and economic value of RDT use in ASPs is weighted towards BSIs in the USA; more evidence must be generated across other disease areas and regions. The use of RDTs is low across HICs and LMICs, and a lack of setting-specific clinical and economic outcome data is a key barrier to RDT uptake. A wider evidence base, combined with robust clinical and economic outcome data, is needed to drive uptake of RDTs. Moreover, effective implementation across a range of resourcing, communication, education, logistic, and interfacing activities is key to maximise RDT adoption. The EWG developed an evaluation framework through which the value of RDTs in an ASP may be more optimally realised than per-patient outcomes only. This paper is a call to action for global stakeholders (i.e. clinicians, laboratory staff, hospital administrators, payers, and policymakers) to:

  • Raise awareness of RDTs available in their setting and maintain close communication with both the ASP team and the microbiology laboratory personnel.

  • Provide and share practical support, training, and resources to facilitate uptake and effective implementation of RDTs in their setting.

  • Encourage the use of RDTs in national reimbursement models, and provide recommendations on RDT use in NAPs and the WHO Model List of EDL.