Introduction

Antimicrobial resistance (AMR) is a threat to global health [1], with a projected 10 million deaths annually by 2050 without intervention [2]. Emergent drug-resistant microbial strains have produced robust discussions around how to manage access to old and new antibiotics responsibly [3]. This “responsible management”, known as antimicrobial stewardship, has assumed a central role in global health and has led to the development of strategies to preserve antibiotics as a class of medicines [1,2,4–6] Strategies to combat AMR have since been developed and refined around several core pillars. The World Health Organization (WHO), for one, has consistently emphasised the importance of awareness, surveillance, reducing infection, stewardship, and research and development [7–9]. The critical need for global collaboration, investment, and research to develop new antimicrobial agents has also featured heavily in the prioritisation of concerns [10–12].

However, despite growing concern, antimicrobial use has increased globally, particularly in low- and middle-income countries (LMICs) [8], contexts within which multiple factors converge to inhibit the prevention and containment of infectious diseases. In parallel, the pace of antibiotic discovery has slowed significantly in the last 60 years. Between 1940 and 1962, over 20 new antibiotic classes were identified [13]. Since then, only three new classes have reached the market. Among these, only one – the class of diarylquinolines – was developed specifically for the treatment of TB [14].

Drug-resistant forms of TB make up one third of the global AMR burden [15], including multidrug-resistant tuberculosis (MDR-TB) – strains resistant to at least isoniazid and rifampicin. Before the approval of bedaquiline (BDQ) in 2014, no new anti-TB compound had entered the market in over forty years [16]. This left patients reliant on lengthy, toxic, and often ineffective regimens with few viable options. The introduction of BDQ addressed a critical gap in treatment options and shifted the landscape of MDR-TB management. BDQ dramatically improved patient experience and treatment outcomes [17], motivating TB stakeholders to advocate for greater access for people with DR-TB. Early access often relied on mechanisms such as “compassionate use”, a framework that allows investigational drugs to be provided outside clinical trials to patients with life-threatening conditions who lack other treatment options [18,19]. However, this development occurred against a backdrop of long-standing challenges in TB programmes, including the emergence of resistance to existing treatments such as rifampicin and isoniazid [20,21]. From this, a bioethical debate emerged about the conflicting concerns of stewardship and treatment prioritisation [22–27].

Stewardship of antimicrobials and access to DR-TB treatment often present conflicting priorities and approaches. Stewardship prioritises antibiotic preservation – including reducing the global reliance on pharmaceutical interventions as a necessary step to maintain their long-term efficacy [28–30]. However, because of the high mortality rate and lack of alternative therapeutic options, TB programming, including care and planning for DR-TB, tends to prioritise expanding access and ensuring the successful implementation of available therapies; in practice, this has often led to antibiotic use that compromises efficacy, particularly in resource-constrained settings where health system infrastructure is weak [21,31]. Despite these competing imperatives, the inclusion of DR-TB in the WHO’s Global AMR Action Plan and other notable reports [1,15,32,33] shows that DR-TB is (at least in policy) a focus of AMR control strategies [34].

Concerns about the excessive use of antibiotics have abounded since their introduction, as illustrated in Podolsky’s [35] and Bud’s [36] histories of antibiotic discovery and distribution, which show how antibiotics became a central and quickly over-depended on part of healthcare service provision. As social scientists and historians of global health have since shown, through initiatives to expand access, antibiotics inadvertently became “quick fixes” to larger public health issues, particularly in LMICs where they were often deployed in part to bridge gaps in under-resourced health systems [37,38]. Often unable to ensure an adequate antibiotic supply through the public sector, in many LMICs loosely-regulated community pharmacies and informal drug shops emerged to fill gaps in formal care, facilitating non-prescription sales and further uncontrolled use of broad-spectrum antibiotics [39–41]. The relative affordability of antibiotics further reinforced this reliance compared to more resource-intensive healthcare interventions, making them an attractive solution especially in LMICs, where financial and infrastructural constraints are pronounced. However, prioritising affordability and scalability often came at the cost of neglecting broader health system strengthening, ultimately leaving many underlying determinants of health inadequately addressed [42,43].

Such deepening antibiotic dependence is captured within the concept of pharamceuticalisation. The focus of a wide body of anthropological and global health scholarship, pharamceuticalisation refers to the process whereby pharmaceutical solutions subsume and replace other, often broader-based interventions in public health policies and practices[cite]. As Jeremy Greene has shown, pharmaceuticalisation in a global context can be traced back to the Essential Medicines movement of the 1970s and 1980s, which aimed to enhance global drug accessibility as a central pillar of primary healthcare [44]. Coupled with the “rational use” movement [45], what constituted an “essential” medicine and ways to avoid misusing it were significantly shaped by the WHO and higher-income countries’ perspectives. While this provided much-needed guidance on which, how, where and when drugs should used, placing antibiotics as the centre of care systems also led to an overemphasis on pharmaceuticals as the critical tool for disease prevention and treatment. This resulted in neglect of the system requirements responsible for their delivery [35].

Although pharmaceuticalisation predates the global health era, it further intensified during this period in the push to ensure wider availability and accessibility of drugs, particularly for HIV, TB, and malaria. A well-rehearsed narrative in critical global health traces how international actors came to increasingly shape healthcare in LMICs, particularly in Africa, which prioritised “vertical” funding and programming, which in turn fragmented service delivery and drew attention away from wider health system strengthening [46,47]. These practices reinforced pharmaceutical-centric approaches and cultivated deepening dependencies on drugs as interventions [48–51]. This reliance highlights the grave risk to health system efficiency, in the context of emergent drug resistance and loss of antibiotic efficacy [38]. With BDQ being one of the few new anti-TB drugs to become available in decades, a significant tension emerges between global health programming’s entrenched logic of ever-expanding access to pharmaceuticals through verticalised approaches, and the emerging imperatives of stewardship in the context of the global AMR emergency – making our analysis particularly pertinent to understanding how these debates have played out in practice. Unlike most broad-spectrum antibiotics, BDQ remains under the tight oversight of national TB programmes and is typically dispensed only through specialist DR-TB services. This exceptional status epitomises the very access–stewardship conflict under review [52,53].

South Africa has the world’s third-largest population of people treated for DR-TB [17,21,54]. As of 2024, MDR-TB accounted for 3.1% of the total TB incidence in the country [55]. Clinical trials in 2012 revealed BDQ to be an effective cure for extensively drug-resistant tuberculosis (XDR-TB) and other resistant strains, with minimal adverse effects. By 2014, South Africa recommended BDQ for treatment for MDR-TB and XDR-TB, prior to the WHO guidance. This prompted international debate about how BDQ would be stewarded responsibly [22–26]. South Africa’s experience with creating access to BDQ is a useful example through which to see how these potentially competing discourses of pharmaceuticalised global health and AMR rationing have played out in a particular setting and programme context.

Our background research involved a scoping review of the evolution of TB containment and control at the intersection of pharmaceuticalisation and drug resistance in South Africa [56]. It showed that the history of TB control in South Africa is one of deepening reliance on pharmaceutical solutions characterised by recurring cycles of drug discovery, optimism, expansion of access, and mounting resistance, culminating in the most recent introduction, optimism, and contestations around BDQ. Building on this formative research, this article provides an in-depth qualitative account of the introduction of BDQ from the perspective of those working within the context of DR-TB control in South Africa. It aims to illustrate how tensions between AMR stewardship and DR-TB treatment priorities played out during BDQ’s initial roll-out and, in doing so, contributes to a deeper understanding of the complexities of balancing these two demands. We do this by (a) contextualising DR-TB care before BDQ was available, and (b) describing key stakeholder perspectives on BDQ access when it first became available and conclude by (c) reflecting on lessons for navigating tensions between AMR stewardship and demand for novel antibiotics. To ensure our analysis centres on the experiences of the TB programme, we specifically gathered insights from stakeholders who are directly involved in DR-TB care, and in the creation and implementation of TB programmes. Our focus was to capture detailed perspectives from those who have a direct role in the administration and policymaking of BDQ in South Africa.

Methodology

This study used an interview-based qualitative design. It was conducted both in South Africa and, when COVID-19-related lockdowns did not allow for travel and face-to-face research, virtually. Interviews were conducted between November 2021 and December 2023. We sought to include participants who had worked in TB and DR-TB treatment, policy, or advocacy in South Africa over the past 25 years, and we aimed in particular to include those with roles in the introduction of or wider debates around BDQ. Participants were recruited through snowball sampling [57], a technique appropriate when participants needed for the research have experience or traits that are highly specific, as in this context [57]. This enabled us to expand the web of contacts and enquiry and allowed for the identification of individuals whose work intersected within shared contexts, such as national TB programmes, advocacy networks, and healthcare delivery settings.

A semi-structured discussion guide, developed by the research team and informed by the study’s objectives, explored four primary areas: (1) roles and experiences in TB control, (2) the history and introduction of BDQ, (3) the balance between antimicrobial stewardship and treatment access, and (4) the implications of potential loss of BDQ to resistance. While the guide provided a consistent structure, it was then tailored to individual participants’ expertise and roles. For instance, questions for policymakers focused on guideline development, while those for clinicians emphasised implementation challenges and patient outcomes. Interviews lasted approximately 45–60 minutes and were facilitated by a postgraduate anthropologist (RR). Interviews were audio-recorded, and field notes were kept to supplement the analysis.

The key stakeholders comprised eight doctors, six activists, five policymakers, and four TB programme managers. All participants had multiple years’ experience in the roles they held, with close first-hand experiences of DR-TB. Of the 23 participants, three were also TB survivors. Three participants withdrew from participation following data collection.

The data were analysed by using thematic analysis to identify and interpret patterns of meaning within the qualitative data, allowing for an in-depth exploration of the various perspectives on DR-TB management and policy implementation. Braun and Clarke’s six-phase framework was followed [58]. First, all interviews were transcribed verbatim, and the primary researcher (RR) reviewed the transcripts alongside detailed field notes to ensure immersion in the data. Initial codes were generated using an open coding approach, assigning descriptive labels to data excerpts that aligned with the study objectives. Once initial codes were developed, they were grouped into themes based on relevance to the research questions and the overarching study objectives.

Results

Discussion

From the perspective of those working within the TB programme in South Africa, stewardship of the new “wonder drug” BDQ became synonymous with access denial. This created an unhelpful polarisation and politicisation of “strawman” camps between opposing viewpoints: on the one hand, there were fears of “wasting” or “ruining” one of the first new antibiotics through the pipeline in decades, and on the other, concerns about enacting a thinly veiled colonial agenda to preserve new drugs for patients in the Global North. This polarisation is particularly relevant in South Africa, where structural challenges intersect with the need for equitable access to lifesaving drugs like BDQ. In this challenging landscape, traditional notions of stewardship became untenable. Even when there were hard policy barriers in place constraining access, providers and patients found themselves bypassing regulations, driven by an ethical imperative to prioritise care.

Global health ethics scholarship has framed this dilemma as a tension between access (the moral duty to relieve present suffering) and excess (the risk that unrestrained consumption accelerates collective harm) [27]. Situating BDQ along this “access–excess” spectrum recasts South Africa’s policy choice somewhat as an ethics experiment privileging distributive justice for today’s patients over a precautionary, future-oriented stewardship ideal. Commentators argue that such trade-offs are inevitable and should be debated openly by a wide range of stakeholders, rather than decided by a small group of technical experts. [27].

These issues are especially acute in South Africa, a country with an entrenched history of poverty, inequality, and racial discrimination. These structural challenges have not only promoted the spread of TB but also compounded the difficulties in treating drug-resistant forms of the disease [78]. Participants in this research powerfully described the daily struggles of seeking to secure medicines and care before the introduction of BDQ, particularly in the throes of the MDR-TB and XDR-TB outbreaks. Doctors consistently emphasised the sense of helplessness they experienced when confronted with abysmal treatment outcomes for their patients. Making it unsurprising that when BDQ emerged as a potential solution, the prevailing sentiment was one of excitement.

Despite the consensus on the inevitability of resistance to BDQ and subsequent novel treatments, participants did not waver in their belief in prioritising access to these drugs. Importantly, they had also carefully considered the argument that novel treatments should be restricted or limited in use; queried whom the preservation of drugs was truly intended to serve; and vehemently fought – often at personal risk – to introduce linezolid to mitigate the potential for the development of resistance. What they were concerned about, however, was the way global stewardship and “drug preservation” discourses implicitly positioned those in low-resource settings as “abusing” antibiotics and suggested that a notion of ‘deserving’ (and thus undeserving) was subtly slipping into these questions, which our participants felt required more interrogation.

The notion of individual behaviour, rather than systemic and structural factors, occupying the centre stage in public health discourse is intimately familiar to social scientists working in the context of TB. Paul Farmer [79], for instance, long argued that the emphasis on adherence and the consequences of defaulting draws attention away from the structural violence that renders patients susceptible to TB. This critique resonates with South Africa’s experience, where the emphasis on individual behaviour often overlooks systemic inequities that influence health outcomes. This emphasis, which was exported around the world through the Directly Observed Tuberculosis strategy (DOTS) model, neglected to consider the impact of structural violence on patients’ ability to attend clinics and placed the responsibility for navigating it on the shoulders of vulnerable communities, emphasising a disconnect between policy and practice when implemented in low-resource settings.

The impacts of these discourses have been well documented, including in South Africa [80–82]. More recently, social scientists working in the context of AMR have observed that much of the emphasis of contemporary stewardship has tended to be placed on the “irrational” behaviour of patients and the restriction and correction of use to protect drug efficacy [83–86]. Building on these critiques, Chandler, Hutchinson, and Hutchison [87], reviewing the collective insights of social scientists within the field of antibiotic use and resistance, have suggested that while policy-level “talk” about protecting vulnerable medicines expands, considerations of protecting vulnerable people have receded – a trend that is particularly concerning for LMICs, as most discussions have been driven by European actors [87] creating a top-down approach to solving a problem that sits predominantly in LMIC contexts.

With BDQ being the first novel TB drug in 40 years, the stakes in making it a first-line drug in contexts such as South Africa were especially high. South Africa was perhaps unsurprisingly placed under considerable scrutiny as to whether the adoption of BDQ was a safe and sustainable strategy [23,88]. From the perspective of our participants, the dominant position within the global TB community was that BDQ be reserved for patients with limited treatment options – an opinion so resounding that it fed into the early WHO guidance [89,90]. This caution was adopted by countries such as India, which approached its roll-out more conservatively. BDQ use in India was initially restricted to specialised centres and governed by strict regulatory frameworks under the Conditional Access Programme (CAP), introduced in 2016 [91]. While this approach aimed to mitigate potential adverse effects and the emergence of drug resistance, it limited access for many patients with MDR-TB, leaving them reliant on older, less effective regimens, and excluded others who could have benefited from its use [92,93]. These barriers likely reduced the overall pace of progress – a result South Africa actively wanted to avoid.

Since then, South Africa has monitored its real-world impact, an approach that allowed the country’s lessons to be shared and ultimately fed into WHO guidance in 2018, which recommended the drug for most patients being treated for MDR-TB around the world [17,94]. The argument for compassion over the rationing of BDQ [23] resonates with arguments to put care for people back into a conversation increasingly framed around care for medicines [87,95]. South Africa’s decision to make BDQ widely available reflects a compassionate approach that has fortunately yielded positive outcomes in the fight against DR-TB. South Africa’s success in championing compassionate use and influencing WHO policy despite global AMR imperatives raises critical questions about pushing back against restrictive drug rationing for the “greater good”.

However, the concerns around the risks associated with introducing these drugs into environments that have historically struggled to ensure adherence are not entirely unwarranted. In 2024, significant signs of resistance to BDQ have rapidly developed [96]. This suggests that an old pattern may be about to repeat, as we have recently observed through our aforementioned scoping review of South Africa’s TB programme [56]. Moreover, the evolving pharmaceuticalisation of South Africa’s TB programme over time has significantly increased reliance on these drugs. This is a trend that, as many critical global health scholars have observed [43,97], was accelerated during the global health era due to the intensified distribution of drugs for TB, HIV, and malaria.

This context gains urgency as South Africa now contends with the complexities introduced by the BPAL(M) regimen, which incorporates BDQ alongside other novel and much-relied-upon drugs: pretomanid, linezolid, and moxifloxacin. This combination offers shorter, less toxic treatments and have been embraced as BDQ and delamanid were before them [94]. However, affordability, access, and resistance management remain critical challenges. South Africa’s experience with BDQ provides valuable lessons for responsibly scaling up BPAL(M), especially in resource-limited settings facing persistent structural barriers.

South Africa’s experience emphasises the increased urgency of the need for stewardship approaches that balance pharmaceutical and non-pharmaceutical interventions. AMR stewardship emphasises the need to prevent excessive use of antibiotics, while ensuring access. However, South Africa’s efforts to make BDQ accessible highlight the challenges of implementing stewardship principles within LMIC contexts, which are historically reliant on pharmaceutical interventions to manage health challenges. This dependency is reflected in the cyclical reliance on quick pharmaceutical fixes driven by entrenched processes of pharmaceuticalisation. Given this, we argue that the focus of AMR stewardship efforts needs to shift from solely regulating the use of drugs to additionally addressing the underlying determinants of health that render individuals vulnerable to infection. For example, discussions around compassionate use were framed almost exclusively in terms of drug availability and immediate patient care, rather than as part of a larger effort to reduce long-term pharmaceutical dependence.

Tending to social and infrastructural factors at the same time as promoting rational drug use will be crucial if stewardship is ever to succeed in LMICs. However, with South Africa’s ongoing struggles politically, socially, and economically, it remains challenging to achieve a universal healthcare system. Acknowledging these constraints, it becomes imperative to strengthen health systems, invest in improving living conditions, and incorporate more comprehensive social care in health system approaches. Such steps are imperative not only for the effectiveness of AMR stewardship efforts but also to break the cycle of dependency on pharmaceuticals as a solution to global health emergencies.

Conclusion

This study highlighted how the effort to expand access to BDQ in South Africa represented a significant shift from the traditional stewardship approaches that have often prioritised preserving antibiotics for future use over meeting immediate patient needs. What we learn is that if those working in LMIC settings are forced to choose between preserving drugs or expanding access, they will inevitably choose access. Further to that, any attempt to enforce stewardship in such settings will likely be thwarted or worked around through community-, provider-, and patient-level collaborations.

What is needed, then, is a conceptual reframing, such that stewardship efforts are not framed by the unhelpful dichotomy of preserving drugs versus preserving life. Instead, there should be a move towards working with affected communities of antimicrobial users to collaborate on strategies that address both immediate patient needs and long-term public health goals.

South Africa’s bold and compassionate approach demonstrates how those working within high-burden settings can prioritise patient needs while still influencing global policy, as seen in its impact on WHO guidance. Effective implementation of AMR stewardship in high-burden, lower-resourced settings must be about building public health capacity and addressing underlying social determinants so that we can preserve life with the effective use of drugs.

Supporting information