Access to Reserve Antibiotics in Latin America and the Caribbean: Situation, Challenges, and Future Directions

Abstract

Access to Reserve antibiotics, which are defined by the World Health Organization’s AWaRe (Access, Watch, Reserve) classification framework as last-resort treatments for multidrug-resistant infections, remains poorly documented in Latin America and the Caribbean despite evidence of increasing antimicrobial resistance in the region, with associated and attributable mortality projected to rise. We examined the landscape of Reserve antibiotic access across Latin America and the Caribbean, identifying the systematic barriers that prevent patients from receiving appropriate treatment. We found that multiple interconnected obstacles—spanning regulatory approval, manufacturer participation, formulary inclusion, procurement systems, and health technology assessment capacity—create compounding delays and gaps in access. The existing barriers also perpetuate inequities where public hospitals face significantly greater constraints to acquire essential antibiotics compared to private facilities. We identified encouraging developments to address these gaps, including emerging regional manufacturing capacity and existing collaborative frameworks. Still, collecting systematic data on access patterns remains insufficient, limiting evidence-based policy responses. Importantly, addressing Reserve antibiotic access requires recognizing that appropriate use encompasses both stewardship and availability of effective treatments when needed. We propose that improving access requires coordinated interventions across five domains: regulatory pathways, production capacity, essential medicines lists, procurement mechanisms, and dedicated national programs. By documenting regional realities and examining practical solutions already implemented in Latin America and the Caribbean, this review aims to inform future evidence generation efforts and policy dialogue toward reducing preventable mortality from treatable resistant infections.

Introduction

Insufficient access to effective antibiotics and appropriate treatments is a major driver of morbidity and mortality related to antimicrobial resistance (AMR).^1–4 According to the Global Research on Antimicrobial Resistance (GRAM) Project, under a “better care” scenario—including expanded antibiotic access and improved clinical management—approximately 92 million deaths could be averted globally between 2025 and 2050.¹ In the Latin American and Caribbean (LAC) region, countries with limited access to antibiotics face disproportionately high AMR-associated mortality rates.⁴ This challenge is particularly acute for Reserve antibiotics—last-resort treatments for multidrug-resistant infections, as per the AWaRe (Access, Watch, Reserve) classification by the World Health Organization (WHO).⁵ Regional data show that patients with serious bacterial infections are treated with Reserve antibiotics at low rates.² Despite this, few countries are prioritizing this important AMR contributing factor even though access to treatments has been identified as a gap in Latin American countries’ AMR national action plans (NAPs).⁶

Most countries in the region have established AMR NAPs, but the aim has generally been to address other factors contributing to the emergence and spread of resistant bacteria.⁶ Primary drivers include inadequate water, sanitation and hygiene (WASH) infrastructure, weak infection prevention and control (IPC) practices in healthcare facilities, and the misuse and overuse of antibiotics in both human and animal health.^3,7–11 Over 50% of hospital antibiotics are prescribed unnecessarily, while three LAC countries—Argentina, Brazil and Mexico—rank among the world’s largest veterinary antimicrobial consumers.^8,12 Limited access to appropriate diagnostics further compounds these challenges.⁷

Countries in LAC have seen significant progress in these areas over the last two decades, with efforts to contain AMR focused on improvements in IPC, antimicrobial stewardship programs, restrictions on over-the-counter sales, and tighter regulations in agriculture.^13–15 However, the NAPs are mostly not fully funded and still present many gaps, revealing a misalignment between the outlined actions and the recommendations in the 2015 Global Action Plan.^6,16,17 Unsurprisingly, the implementation of AMR NAPs and relevant AMR policy is lagging and is uneven both at the national and regional levels. Barriers to effective implementation include resource constraints, funding inequities, and inadequate human capacity for translating NAP objectives into practice.¹⁸

Within this context, regional resistance data show progressive deterioration. Between 2014 and 2016, carbapenem nonsusceptibility in Klebsiella pneumoniae increased significantly across the region, while Acinetobacter baumannii already exceeded 50% carbapenem resistance in two-thirds of reporting countries.¹⁹ By 2019, carbapenemase-producing organisms had become endemic across the region.²⁰ More recently, a systematic review and meta-analysis of LAC intensive care units found that nearly one-third of Gram-negative isolates now demonstrate carbapenem resistance, with A. baumannii exceeding 70% resistance rates.²¹ Country-level data from Argentina reflect the clinical consequences of this burden: across 164 intensive care units, infections by multidrug-resistant organisms affected 15.1% of patients and carbapenemase-producing Enterobacterales colonization occurred in 24.7%, both associated with prolonged length of stay and 27.1% mortality.²² These resistance patterns translate into a substantial regional mortality burden: in LAC, AMR was directly attributable to 81,000 deaths and associated with an additional 240,000 deaths in 2021.¹ Projections suggest that by 2050, AMR-associated mortality in the region could approach 650,000 deaths, with 148,000 directly attributable—positioning LAC among the regions most severely impacted by rising resistance.¹ Yet clinicians across the region remain reliant on older, more toxic agents such as colistin, as newer Reserve antibiotics are unavailable.^23,24

Addressing this mounting burden requires confronting a critical and often overlooked gap: while LAC countries have made significant efforts toward resistance containment, access to Reserve antibiotics needed to treat the most resistant infections is severely constrained. This review focuses on the current access landscape as an essential pillar of the regional AMR response. We aim to bring visibility to one of the region’s most pressing challenges that must be addressed to reduce AMR-related morbidity and mortality now and in the future.

Access to Reserve Antibiotics in LAC: Status and Barriers

Status Snapshot

Across the LAC region, low consumption of Reserve antibiotics despite documented clinical need reveals persistent gaps in registration and patient availability, which lag behind countries in the Global North.^2,10,25 This is partly attributable to prolonged registration processes where regulatory approval for innovative medicines averages 38 months regionally, with Reserve antibiotics—which comprise a significant portion of newer antibacterial agents—disproportionately affected by these delays.²⁶ Both generic and new Reserve antibiotics face significant access barriers; new agents especially encounter severe challenges for both registration and pricing.²⁷ Pharmaceutical companies filed for registration for only 14% of off-patent essential antibiotics in ten or more LAC countries, and filed for registration of Reserve antibiotics in only two countries on average, compared to 16 countries for Access antibiotics.²⁸

Even with successful registration, multi-year authorization-to-availability lags are common in LAC. Recent analysis of innovative medicines indicates lengthy delays measured from regulatory approval to patient access, with wide variations across countries of 59 to 83 months. These timelines also vary by access pathway, whether through out-of-pocket purchase in private markets, private insurance reimbursement, or public sector coverage.^26,29 Moreover, public versus private sector availability creates a two-tiered system of access. Public hospitals consistently lag private facilities for Reserve antibiotic availability, with health technology assessment (HTA) mechanisms and procurement processes that require months or even years to incorporate and make available new Reserve antibiotics within health systems.^30–32

Pricing patterns in LAC impose substantial access barriers for Reserve antibiotics in both the public and private sectors, with affordability identified as a major unmet barrier that undermines successful management of drug-resistant infections.³³ Price variations exist across health sectors in the region, which can result in insufficient access in many countries, especially for innovative products.²⁶ This pattern of inadequate access indicates that pharmaceutical companies may be neglecting use of mechanisms they usually employ to support post-approval patient access to their products, and especially Reserve antibiotics.^28,34 While this neglect may be due in part to the poor market potential of these treatments, the companies are also actively choosing to avoid registration in many LAC markets despite the critical public health value of these last-resort treatments.

Market and Regulatory Barriers

Limited registration filings reflect systematic market entry barriers across low- and middle-income country (LMIC) markets, including LAC, with Reserve antibiotics having severe registration delays. For example, Merck’s ceftolozane-tazobactam (ZERBAXA™) was approved by the US Food and Drug Administration (FDA) in 2014, with a supplemental New Drug Application approval in 2019.^35,36 As of 2022, this product was only registered in nine LMICs in LAC.³⁷ Similarly, cefiderocol (FETROJA^®), which received FDA approval in 2019, remains unregistered LAC-wide as of 2025.³⁸ Efforts do exist to address this specific access gap—namely, a license and technology transfer agreement between the originator Shionogi and the Global Antibiotic Research and Development Partnership (GARDP), aimed at accelerating access to cefiderocol in 135 countries, including all of LAC.³⁹

Lengthy regulatory approval processes create compounding barriers that discourage market entry in LAC pharmaceutical markets, with conditions deteriorating rather than improving over time. These extensive timelines create economic risks for manufacturers that are commercializing new treatments with uncertain sales potential, such as Reserve antibiotics. LAC country-specific data illustrates the administrative burden: Brazil’s National Health Regulatory Agency (ANVISA) median approval time was 795 days (approximately 26 months) for new medicines between 2013–2016, but more recent FIFARMA data shows it is now over 36 months.^26,40 Pfizer’s linezolid took over 5 years from submission to regulatory approval in Brazil.⁴¹

Prolonged timelines stem from regulatory requirements that mandate traditional Phase I–III trial completion, infrequent adoption of expedited approval pathways or priority drug programs, irregular updates to regulatory frameworks, and limited implementation of international harmonization guidelines, as well as assessment backlogs at regulatory agencies—factors that collectively delay both registration and post-approval availability.^26,42 Analysis of broader healthcare access patterns shows these delays have worsened, with average approval-to-availability timelines increasing from 57 months to 67 months for innovative medicines.^26,43

Market dynamics create unfavorable conditions for Reserve antibiotic availability throughout LAC. Companies still active in antibiotic markets face tough conditions characterized by fragile supply chains, low margins for older medicines, small patient numbers for newer medicines, and variations in regulatory requirements.⁴⁴ Stewardship restrictions, the risk of resistance development over time, and short treatment courses add further pressure on already fragile antibiotic markets.^45,46

The availability status of five Reserve antibiotics on the WHO EML illustrates the variation across the region: as of 2023, colistin injection, polymyxin B, aztreonam, ceftazidime-avibactam and fosfomycin injection were all registered in Colombia, while none were registered in Guatemala—a disparity consistent with the influence of market size and commercial attractiveness on registration decisions across LAC economies.⁴⁷

The economic disparities discourage both manufacturer participation and competitive pricing. Manufacturing concentration exacerbates these vulnerabilities, with China accounting for approximately 40% of global active pharmaceutical ingredient (API) production, creating fragile supply chains that increase distribution costs and supply risks.⁴⁴ In several National Regulatory Authority of Regional Reference (NRAr) markets, a share of finished products is made locally, but most APIs—and many finished products—are imported (largely from China and India), and exports remain modest and mostly intra-regional.⁴⁸ This vulnerability is amplified by LAC countries’ heavy dependence on pharmaceutical imports, with countries importing 55–90% of their pharmaceutical consumption according to 2019 data, creating additional supply chain risks, particularly for specialized products like Reserve antibiotics.⁴⁹ While diversification of manufacturing sources is often proposed as a solution, local or regional production can increase costs due to lost economies of scale and upfront investment needs; nevertheless, these costs may be justified by the benefits of more reliable access to critical medicines—especially when supported by government mechanisms such as industrial policy.^50,51

Progressive manufacturer withdrawal from antibiotic markets intensifies these challenges. Brazil exemplifies this trend, where domestic API production declined from 55% to 5% over four decades, with the remaining 5% consisting of low-technology, low-value products and no production of antibiotic API.^52,53 The scale of global manufacturer exit is evident in approval data: only two new antibacterial medicines gained approval from at least one stringent regulatory authority—namely, the FDA and/or the European Medicines Agency (EMA)—between 2010 and 2021, representing a dramatic decline in antibiotic innovation, with seven of twelve companies that brought antibiotics to market in the prior decade going bankrupt or exiting the business.^28,54 As companies go bankrupt or exit, manufacturing operations and supply chains are disrupted, reducing production capacity and supply stability for generic and newer agents alike.⁵⁵ Many of the remaining companies do not pursue regulatory approval in LAC markets given the administrative burden and uncertain returns.

Health System Barriers

When drugs are both registered and available, significant barriers still prevent effective patient access within health systems. The 2021 AMR Benchmark analysis of 166 antibiotics and antifungals across 102 LMICs, including nine LAC countries, reveals substantial implementation gaps. Only 54 products are covered by any access strategy—mechanisms companies use to provide access to their products, such as equitable pricing and distribution arrangements—across all companies studied.^28,34,56 Off-patent medicines are particularly neglected, with only 34 of 131 generic products having access strategies compared to 7 of 17 on-patent medicines.²⁸ This gap is most severe for Reserve antibiotics, for which companies often have minimal or no access strategy.

Financial constraints—especially within public healthcare systems—severely limit access to Reserve antibiotics in LAC, with the high cost of these agents often placing them out of reach for hospitals and patients, even when there is clinical need.³³ Importantly, registration alone does not guarantee patient access: in Latin America, there is a 27% gap between medicines with regulatory approval and those achieving any form of patient availability, with innovative drugs taking an average of over 2.5 years from approval to reach patients.^26,33 This disconnect reflects a combination of factors including supply chain, procurement, reimbursement, and health system limitations.^26,28

The case of ceftolozane-tazobactam illustrates this disconnect between registration and actual patient access. By 2022, despite being registered in nine LMIC countries in the LAC region, it remained unavailable in four of them.^28,37 This underscores the importance of comprehensive access strategies that address not only registration but also pricing, supply, procurement, and reimbursement mechanisms to ensure that Reserve antibiotics reach patients who need them.

National essential medicine list (EML) inclusion is a critical enabler of these mechanisms, since inclusion on an EML underpins public sector reimbursement and institutional procurement decisions.³³ The registration-availability gap is reflected in national EMLs across LAC countries, which typically include older Reserve antibiotics like linezolid and colistin but lack newer-generation agents specifically designed for carbapenem-resistant infections. The clinical urgency is stark: in Argentina, carbapenem-resistant K. pneumoniae prevalence reached 40% in bloodstream infections, 34% in pneumonia, and 44% in urinary tract infections in 2024, with associated mortality rates exceeding 50% in bacteremia cases.^57,58 Yet access to newer Reserve antibiotics like ceftazidime-avibactam and aztreonam-avibactam is hampered by high costs and economic barriers, with pharmaceutical companies viewing the market as financially unviable despite the urgent medical need.⁵⁸

EML inclusion relies heavily on evidence-based selection that considers public health relevance, clinical benefits and harms, and cost-effectiveness factors.⁵⁹ Furthermore, many LAC countries have established decision-making processes incorporating HTA to inform healthcare system coverage and national EML inclusion.^60,61 Countries with more developed HTA systems, such as Brazil, use cost-effectiveness criteria systematically to evaluate technologies for public healthcare incorporation.⁶²

Generating the needed evidence for HTA processes is challenging, especially in LMICs, where limited financial resources, skilled human resources, and data availability constrain evidence generation capabilities.⁶³ In LAC, governments and academic institutions have stepped in to carry out this work, with the latter constituting 34% of HTA-conducting organizations in the region.⁶⁴ Public teaching hospitals lead hospital-based HTA, accounting for 83% of such efforts.⁶⁰ At the institutional level, however, these efforts remain constrained by lack of specialized training and dedicated human resources, limited experience with innovative contracting mechanisms, legal complexity, and the absence of centralized clinical data for evaluating treatment outcomes.^60,65 Compounding these resource limitations, HTA for antibiotics carries additional methodological challenges, including capturing long-term benefits from reduced resistance, predicting resistance evolution, and quantifying broader societal impacts.⁶⁶

Brazil exemplifies these regional challenges despite having one of LAC’s most developed HTA systems. While the country’s essential medicines list includes older Reserve antibiotics (linezolid, colistin), the Brazilian National Committee for Technology Incorporation (CONITEC) has received zero requests—from either government agencies or external stakeholders, including pharmaceutical companies—for assessing newer-generation Reserve antibiotics such as ceftazidime-avibactam and ceftolozane-tazobactam, despite their regulatory approval.^67,68

The consequences of national EML exclusion are also evident in Peru, where only colistin from the Reserve category appears in the national essential drug registry despite regulatory registration of other Reserve antibiotics and documented resistance rates of 44–52% to third-generation cephalosporins among Escherichia coli and K. pneumoniae.²³,46 A 2019 point prevalence survey involving ten public hospitals found Reserve antibiotics accounted for only 0.6% of prescriptions, demonstrating how national EML gaps create systematic access barriers that persist even when resistance rates would justify Reserve antibiotic use.²³ Similar patterns have been observed in other upper middle income countries in the region: there was no documented use of Reserve antibiotics based on the 2019 AWaRe classification in Guyana and Saint Lucia; notably, Saint Lucia’s national EML did not contain any Reserve antibiotics, and Guyana’s included only one, despite both facing widespread multidrug resistance.^69,70

Formulary selection is not keeping pace with resistance epidemiology, increasing mortality risk for patients with serious bacterial infections caused by multidrug-resistant pathogens in the region. Regional surveillance data underscores this critical gap. A retrospective analysis of 58,909 isolates collected across 12 LAC countries—73% from Brazil—found an overall carbapenemase prevalence of 81.1%, with carbapenem-resistant Enterobacterales (CRE) comprising the majority (65.3%), followed by A. baumannii complex (22.1%) and Pseudomonas aeruginosa (12.7%).⁷¹ Despite this high burden, as of 2021, 35% of LAC countries listed no Reserve antibiotics on their national EML, with countries listing a median of only 1 Reserve antibiotic—primarily older agents like colistin and linezolid.⁷⁰ Additionally, an Argentinian study showed that newer agents such as ceftazidime-avibactam significantly reduced mortality in CRE bacteremia compared to older drugs, such as colistin.⁵⁸

Beyond the policy-level barriers created by EML exclusion, operational challenges at the hospital level further impede access. In LMICs, access to antibiotics is constrained by inadequate health infrastructure, restricted budgets, inadequate or fragmented supply chains, and ineffective procurement schemes.⁷² These compounding barriers sustain the two-tiered system reported across LAC. In Argentina, a 2024 survey of 199 health institutions found that while 74% of private facilities had ceftazidime-avibactam available for directed treatment, only 60% of public institutions had access, with the disparity widening further for empirical use, where private sector availability (50%) nearly doubled that of the public sector (27%).³⁰

Considerations for Action

The barriers to Reserve antibiotic access in LAC operate as interconnected challenges rather than isolated problems. High costs place Reserve antibiotics out of reach for public hospitals, while small market size discourages manufacturer participation and investment. Lengthy regulatory timelines and companies’ decision-making for Reserve antibiotics delay market entry, while non-inclusion in national EMLs limits systematic institutional availability by removing these agents from priority frameworks that guide hospital formularies, HTA evaluation pathways, and procurement decisions. Even where drugs are registered and listed, operational constraints—limited budgets, fragmented supply chains, inadequate HTA capacity—block hospital-level availability. The result is a reinforcing cycle where registration does not ensure availability, and availability does not ensure access, perpetuating the two-tiered system observed across the region (Figure 1). Breaking this cycle requires integrated interventions addressing multiple barriers simultaneously.

Figure 1.

Interconnected barriers constraining Reserve antibiotic access in Latin America and the Caribbean.

Accelerating Regulatory Pathways and Reliance

Several of the most immediate barriers, such as lack of registration submission and lengthy delays, could be addressed through accelerated regulatory pathways and greater use of reliance mechanisms. The Pan American Network for Drug Regulatory Harmonization (PANDRH) provides a framework for work-sharing and collaborative registration reviews among LAC regulatory authorities, though uptake for antibiotics remains limited.⁷³ Thirteen of 20 LAC regulators have adopted regulatory reliance mechanisms, primarily recognizing approvals from the European Medicines Agency, US Food and Drug Administration, and Health Canada.⁷⁴ Similarly, Caribbean Community (CARICOM) countries employ collective reliance on NRAr through the Caribbean Regulatory System (CRS).⁴⁸ The Pan American Health Organization (PAHO) Strategic Fund incorporates WHO Prequalification (PQ) as a quality assurance mechanism for procurement—in 2023, WHO’s PQ program issued its first invitation for Reserve antibiotic evaluation (cefiderocol), expanding prequalification to multidrug-resistant bacterial infections and presenting an additional reliance pathway that could facilitate Reserve antibiotic access in LAC.^75,76 Moreover, since 2016, PAHO’s Strategic Fund has also allowed for procurement of products that are approved and marketed in at least one NRAr, further demonstrating how reliance mechanisms can facilitate both registration and procurement.⁷⁷ Broader adoption and harmonization of such approaches could create stronger incentives for manufacturers to file across multiple LAC countries while reducing the administrative burden.

Promoting Local and Regional Production Capacity

Dependence on pharmaceutical imports creates serious vulnerabilities for LAC health systems, particularly for specialized products such as Reserve antibiotics. Investing in local or regional production capacity—for both active pharmaceutical ingredients and finished products—could reduce reliance on fragile supply chains and improve access. Recent progress includes Argentina’s 2024 regulatory approval of the first regional ceftazidime-avibactam generic (CEFTAAVI-Bagó^®), demonstrating regional manufacturing capacity for newer Reserve antibiotics. Brazil’s Product Development Partnerships (PDPs) program illustrates how public-private collaboration can enable technology transfer and domestic production, though Reserve antibiotics have not yet been prioritized.^78–80 Given the low-volume nature of Reserve antibiotics, country-level manufacturing may face economic challenges as fragmented markets can drive up costs—underscoring the importance of coordinated approaches. Regional initiatives provide frameworks for coordinating investment and demand, including PAHO’s Regional Production Platform and the Southern Common Market (MERCOSUR) Ad Hoc Committee to Promote Regional Production Capacity (CAHECPR).^81,82 Extending these mechanisms to Reserve antibiotics could enhance supply security, reduce costs, and ensure sustainable access.

Enhancing HTA and Updating National EMLs

Outdated national EMLs create barriers by failing to prioritize newer Reserve antibiotics, even where resistance rates justify their clinical use. This omission limits institutional availability through negative consequences on hospital formularies and procurement decisions. Countries could strengthen HTA capacity through regional knowledge-sharing networks such as the Health Technology Assessment Network of the Americas (RedETSA) and joint evidence reviews to support evidence-based EML updates.⁸³ Harmonizing national lists with the World Health Organization (WHO) Model List of Essential Medicines would align selection with evolving resistance patterns and clinical needs. Furthermore, regional resistance surveillance data from networks such as the Latin American and Caribbean Network for Antimicrobial Resistance Surveillance (ReLAVRA+), which spans 33 countries across the region, could further guide these processes—though country-specific resistance patterns, healthcare system structures, and resource contexts must inform how this data is translated into national EML and HTA prioritization decisions. For countries with limited HTA capacity, WHO guidance on antibiotic introduction recommends starting with budget impact assessments that evaluate affordability relative to the treatment population, recognizing that while Reserve antibiotics have high unit costs, their small target populations may make them financially acceptable.⁸⁴

Pooling and Coordinating Procurement

Fragmented procurement processes hinder both accessibility and affordability, particularly when national EMLs are outdated. At the regional level, pooled procurement mechanisms such as the PAHO Strategic Fund have proven effective at securing lower prices for high-cost medicines and improving availability, with demonstrated capacity to reduce price disparities and increase access.⁸⁵ Additionally, several LAC countries allow public-sector procurement via the PAHO Strategic Fund/Revolving Fund without full national marketing authorization, leveraging NRAr/WHO quality assurance to expedite access.⁴⁸ However, PAHO’s Strategic Fund currently includes only one Reserve antibiotic—ceftazidime-avibactam, as of 2021—representing an opportunity for portfolio expansion.⁸⁶

At the national and subnational level, coordinated procurement can similarly aggregate demand while integrating stewardship requirements. Argentina’s provincial High-Cost Antimicrobial Drug Banks (MAAC) exemplify this approach. Established in Buenos Aires and Tucumán provinces in response to urgent clinical need and economic barriers to accessing new Reserve antibiotics, these banks combine centralized procurement with evidence-based treatment algorithms and rigorous auditing systems to ensure appropriate use.^58,87 Early outcomes from Buenos Aires Province demonstrate both the reach and the stewardship value of this model: 175 treatments were initiated, with 15 of 175 requests (9%) rejected following audit review. Among 94 completed treatments, duration was shortened in 15 cases (16%) and therapy was de-escalated in 16 cases (17%) once clinical stability was achieved.⁸⁸ Though scaling such approaches nationally remains challenging given Argentina’s highly fragmented healthcare system, the model demonstrates that coordinated procurement mechanisms can overcome economic barriers while preserving antibiotic efficacy through built-in stewardship.⁸⁸ Realising this potential at scale, however, requires the cross-sectoral coordination that currently remains absent.

Coordinating AMR Access Through National Programs

The interventions described above—regulatory acceleration, local production, EML harmonization, and coordinated procurement—currently operate in isolation across different government departments and programs. Vertical programs such as those for HIV, tuberculosis, malaria, and immunizations, among others, demonstrate an alternative approach: dedicated entities with sustained funding and technical capacity can rapidly incorporate new treatments into national guidelines and EMLs, negotiate access to high-cost medicines, facilitate technology transfer for local production, coordinate with regulatory and procurement authorities, and aggregate demand across fragmented systems.⁸⁹ In LMICs, new HIV and TB medicines are typically included in national essential medicines lists within a median of one year after their addition to the WHO Model List of Essential Medicines, reflecting the responsiveness of vertical programs to global guidance.⁹⁰ Brazil’s public manufacturers, such as Fiocruz and Butantan, play a central role in producing vaccines prioritized for the national immunization calendar, supplying most doses to the public sector through ongoing investment, technology transfer, and partnership with the Ministry of Health.^91–93

Despite most LAC countries having AMR national action plans, few have operational programs with dedicated budgets and authority to prioritize Reserve antibiotic needs, rapidly update treatment guidelines and EMLs, negotiate access to new agents, or consolidate institutional demand.⁶ Establishing such programs—with resources to commission HTA evidence, advocate for EML inclusion, coordinate pooled procurement, facilitate technology transfer, and set national treatment guidelines, including under a stewardship lens—could transform fragmented activities into systematic approaches addressing the interconnected barriers documented throughout this analysis (Table 1).

Table 1.

Proposed Interventions Mapped to Reserve Antibiotic Access Barriers in Latin America and the Caribbean

		Areas of Intervention
		Regulatory Pathways & Reliance	Local/Regional Production	EML & HTA Strengthening	Pooled Procurement	National AMR Programs
Barriers	Regulatory complexity	Reduce administrative burden through reliance; expedite pathways for unmet needs; leverage PANDRH harmonization	—	—	Leverage PAHO Strategic Fund procurement using NRAr/WHO PQ reliance	Advocate for priority reviews based on public health need
	Market & supply fragility	—	Reduce import dependence through regional manufacturing; strengthen local manufacturing; leverage MERCOSUR/PAHO platforms	—	Establish strategic stockpiles and long-term supply agreements; negotiate lower prices through demand aggregation	Guide prioritization of national manufacturing capacity for critical AMR agents, focusing on technology transfers
	EML misalignment	—	—	Align national EMLs with WHO Model EML; leverage ReLAVRA+ surveillance data to inform updates; harmonize regionally	EML inclusion as prerequisite for inclusion in pooled procurement portfolios	Commission HTA evidence; advocate for EML inclusion; harmonize clinical formularies
	HTA capacity constraints	—	—	Conduct RedETSA joint evidence reviews; foster regional data sharing	—	Secure dedicated HTA funding
	Procurement fragmentation	—	—	—	Expand PAHO Strategic Fund portfolio; establish regional pooled tenders; aggregate demand	Centralize or coordinate national procurement; develop demand forecasting tools; establish subnational high-cost drug access programs; secure private sector reimbursement pathways

Conclusion

A critical challenge emerges from this review: for most LAC countries, systematic data on Reserve antibiotic registration status, EML inclusion, pricing, and access patterns are absent or insufficient, and where data exist, they are concentrated in larger economies such as Argentina and Brazil. This evidence gap is itself a primary finding—it prevents the region from fully understanding the scale and root causes of the access problem it faces, thus limiting evidence-based policy responses. Addressing this gap must be a prerequisite for any subsequent coordinated action.

Beyond the data deficit, this review documents systematic barriers preventing access to Reserve antibiotics across LAC despite rising carbapenem resistance and documented clinical need. Limited manufacturer participation, lengthy regulatory delays, outdated national EMLs, financial limitations, fragmented procurement, and constrained HTA capacity compound one another to create severe access gaps regionwide. Where Reserve antibiotics are available, a two-tiered system reinforces inequities, with public hospitals facing greater constraints than private facilities. The mismatch between resistance epidemiology and Reserve antibiotic availability reflects a regional pattern requiring coordinated intervention—one that remains understudied, with limited published evidence documenting Reserve antibiotic access barriers and use patterns.

Addressing these gaps requires recognizing that appropriate antibiotic use encompasses both stewardship to preserve efficacy and availability of effective treatments. The five intervention domains proposed—accelerating regulatory pathways through reliance mechanisms, promoting local and regional production, enhancing HTA and updating national EMLs, pooling procurement, and establishing dedicated national AMR programs—are grounded in approaches already demonstrated in LAC contexts across health programs, from subnational drug banks to vaccine production partnerships and regional pooled procurement mechanisms. These efforts must be guided by improved data collection on Reserve antibiotic access across the full diversity of LAC countries. The WHO 2030 Agenda provides a relevant framework for this work, with its emphasis on equitable access to essential medicines and coordinated national responses to AMR—goals that are largely unmet for Reserve antibiotics across the region. GRAM projects that improved access to appropriate antibiotics could avert 92 million deaths globally between 2025 and 2050.¹ Transforming LAC’s fragmented initiatives into systematic approaches requires political commitment, dedicated financing, and operational AMR programs with authority to coordinate across regulatory, procurement, and clinical domains. Without such action, the gap between resistance burden and treatment availability will widen further, perpetuating preventable mortality from infections that effective antibiotics could treat.^1,2,4,58

Author Contributions

SR conceived the review, developed the outline, conducted the literature search and analysis, and drafted and finalized the manuscript. YN, MS, and WC contributed local data, contextual insights, and case examples from Argentina, and critically reviewed the manuscript for regional accuracy and relevance. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

YN reports personal fees from Pfizer and Bagó, and grants from Roche, outside the submitted work. SR is an employee of GARDP. The authors report no other conflicts of interest in this work.