Is the world crippled by antimicrobial resistance, or simply lacking information?

KEYWORDS:

• Antimicrobial resistance
• antibiotic misuse
• antibiotic overuse
• geographic variation in AMR
• antimicrobial stewardship programs

1. Introduction

Antimicrobial Resistance (AMR), a growing danger, is estimated to cause 10 million annual deaths by 2050 [1]. The origin of this issue can be traced back nearly 100 years to the discovery of arsphenamine and penicillin in 1907 and 1928, respectively. Arsphenamine was an initial breakthrough in antimicrobial therapy when introduced as the treatment for syphilis; however, resistance soon developed over time, diminishing its long-term efficacy. Furthermore, incorrect prescribing and dispensing of penicillin led to its misuse, leading to resistant strains emerging quickly by 1945, illustrating their adaptive nature as well as an arms race between their evolution and antibiotic development [2].

AMR reduces effectiveness of antimicrobial medicines, which may increase hospitalization, and mortality [3]. Overuse and misuse of antimicrobials across human medicine, veterinary medicine, and agriculture further exacerbate the problem while driving up healthcare costs; by some estimates AMR costs have reached more than $4.66 billion each year in the United States (US) alone [4]. A systematic review and meta-analysis by Moses Ocan et al., analyzed the literature for studies focusing on self-medication of antibiotics in in low and middle income countries (LMICs) and included 34 cross-sectional observational studies with 31,340 participants [5]. The study found that the major sources of antimicrobials used in self-medication in LMICs were pharmacies (61.8%) and leftover drugs. The studies reported that respiratory tract infections, gastrointestinal issues, and symptoms related to malaria were the most common reasons for self-medication.

A systematic review by Dadashi M et al., focused on Stenotrophomonas maltophilia, a pathogen increasingly recognized for its multi-drug resistance, especially in hospital environments. The study showed that the type of pathogen and geographic location substantially affect the prevalence of AMR [6]. For example, resistance rates to trimethoprim-sulfamethoxazole (TMP/SMX), a key antibiotic used in treating S. maltophilia infections, were highest in Asia, Europe, and America. Additionally, a meta-analysis focusing on methicillin-resistant Staphylococcus aureus (MRSA) colonization in elderly care center residents found a global prevalence rate of 14.69%. Significant predictors were male gender, history of antibiotic use, and previous MRSA infections [7].

Historically, humans have responded to AMR with scientific innovation and policy measures; yet, the issue persists, which pinpoints gaps in these approaches. This editorial aims to shed light on such potential shortcomings and attempt to answer whether AMR is a crisis of lack of information or systemic failure to effectively apply existing knowledge.

1.1. Recent advancements in tackling AMR

AMR poses a complex scientific challenge, requiring multifaceted approaches and innovations that target various aspects of AMR. Over the past few years, several approaches have emerged.

Researchers at the University of Zurich have developed a novel antibiotic class utilizing the natural peptide thanatin. This targeted approach tackles Enterobacteriaceae bacteria, including notorious strains like K. pneumoniae, both in lab settings and in animal models. Notably, this class demonstrates minimal resistance emergence due to its unique mechanism of action, which disrupts a vital bacterial protein bridge [8].

Another promising breakthrough came from Maynooth University, where researchers have developed a new class of fluorescent anionophores called ‘squindoles’ [9]. These compounds, designed to combat AMR, disrupt sodium and chloride concentrations within Gram-positive bacterial cells, causing cell death. Some squindoles show a strong affinity toward chloride ions, while cell assays and proteomics profiling have revealed their anion transport abilities; one specific squindole showed significant inhibitory actions against Staphylococcus aureus and MRSA strains, thus offering promising therapeutic approaches toward AMR treatment.

Microbial dark matter – composed largely of unexplored microorganisms with unknown genomic potential – provides another pathway toward discovering biological resources that have yet to be exploited. Machine learning (a subset of artificial intelligence, or AI) has enabled the identification of more than 100,000 novel metagenome protein families (NMPFs). These discoveries indicate an immense, undiscovered protein sequence space, suggesting opportunities for creating effective antibiotics against multi-resistant strains [10,11].

The fight against AMR extends beyond traditional antibiotics. Scientists are exploring the development of antimicrobial materials and targeted drug delivery systems. This includes NorA efflux pump inhibitors and erythrocyte membrane-encapsulated systems [12].

Early diagnosis is essential in managing and limiting the spread of resistant infections. A novel diagnostic technique employing deep learning (DL) has been developed to differentiate between Escherichia coli cells that are responsive to antibiotics and those that are resistant. This method can deliver results in as short a time as 30 minutes, substantially enhancing the speed and efficiency of diagnosis compared to conventional methods [13].

1.2. Gaps in AMR response

Studies in the literature have identified several limitations to the current strategies in combating AMR. This includes gaps between policy establishment and implementation, lack of policy monitoring, poor surveillance systems, shortcomings in research methodologies and data collection, and lack of proper funding.

A recent systematic analysis, comprising 114 countries, conducted from 2020 to 2021, reported a substantial gap in AMR response across these countries [14]. Implementation of National Action Plans (NAPs) against AMRs has faced considerable hurdles worldwide, particularly among low- and middle-income countries (LMICs). Many countries have created NAPs, yet many struggled with active implementation due to multiple reasons, including insufficient political commitment, budget restrictions, and local context incompatibilities [15]. As reported by WHO-approved NAPs, only 59% are aligned with its Global Action Plan strategic objectives, and implementation has been severely limited in Africa due to lack of resources, awareness, and coordination among key stakeholders. Pakistan provided an insightful case study on the challenges associated with implementing regulatory approaches amid local political and economic dynamics, underscoring the significance of understanding power dynamics as well as systemic constraints in policy implementation [16].

Addressing AMR requires countries to recognize their responsibility in prioritizing and integrating AMR One Health programs into national operating costs instead of depending on external funding alone. Implementation of One Health approaches requires developing an integrative strategy encompassing human, animal, environmental, and agricultural health sectors; however, many countries, particularly LMICs, face difficulty allocating adequate domestic resources for such initiatives. Such dependence leads to overreliance on international aid and external funding sources that are unsustainable over the longer run. Countries must develop innovative organizational approaches in order to effectively combat AMR. Such measures might include developing strong funding mechanisms, integrated surveillance systems, and multisectoral coordination efforts. To do this effectively and sustainably requires not only allocating government funds but also setting up effective systems to oversee these resources and ensuring AMR initiatives can be sustainably funded and effectively executed. Strengthening national capacities such as laboratory infrastructure, workforce training programs, and public awareness campaigns is vital to creating an effective One Health AMR response. Countries must ensure AMR strategies are integrated into wider public health and development agendas, aligned with the Sustainable Development Goals to provide a more holistic approach to AMR containment.

There are several obstacles facing the surveillance of AMR, including staffing limitations, training needs, laboratory infrastructure issues, and data capture and quality assurance issues [17]. Communication barriers further exacerbate these difficulties, leading to delays in reporting laboratory results as well as reduced confidence [18]. Concerns have also been expressed regarding the sustainability of surveillance programs in Low- and Middle-Income Countries (LMICs), where external funding is often required for implementation; empirical evidence demonstrates a general lack of awareness and knowledge regarding appropriate antibiotic use and AMR in these regions [19,20].

Regarding gaps in AMR research, recent studies have identified several key barriers in study design, methodology, and the evaluation of interventions, particularly in antimicrobial stewardship programs (AMS). An Indonesian study conducted in hospitals found significant barriers to AMS implementation. These challenges included ineffective resource allocation, insufficient institutional commitment for mandatory antimicrobial surveillance under hospital accreditation, conflicts between profit generation and interprofessional relationships, prohibitive costs of bacterial culture testing, and unreliable microbiology laboratory infrastructures [21]. The complexity of AMR mechanism and lack of interdisciplinary collaboration were also identified as potential gaps that hinder the advancement in AMR research [22].

AMR is further compounded by insufficient funding across different sectors. These include public health, agriculture, environmental health, and drug discovery. In public health, for example, there are barriers to effective surveillance of AMR due to weak laboratory infrastructure, limited staff capacity and training, communication issues, and a lack of availability of consumables, diagnostics, and reagents. These challenges are exacerbated by reliance on external funding to strengthen laboratory capacity and implement AMR surveillance programs [23].

Reduced US funding could pose a threat to global efforts against AMR, potentially undoing gains made in drug development and public health initiatives [24]. While the United States has made strides toward combating AMR by creating its National Strategy for Combating Antibiotic-Resistant Bacteria, as well as supporting research through funding increases proposed in President Biden’s FY 2023 budget request, protectionist policies could thwart global AMR efforts and cause irreparable harm [25].

Critics have pointed to recent US policies such as the Inflation Reduction Act and the 2022 Chips and Science Act as examples of protectionism that create an uneven playing field for trade, subvert multilateral agendas, and undermine multilateralism. Critics note these acts reflect an ‘America First’ ideology, which could signal a move away from global cooperation toward prioritizing domestic security and resilience at the expense of international collaboration vital for combating AMR, as the US plays an essential leadership role worldwide by pooling global resources for antibiotic research and development globally [26].

The WHO has reported a global shortage of antibiotics, with current clinical developments failing to address drug-resistant bacteria effectively [27]. The shortage is especially acute in resource-limited settings where vulnerable groups such as new-borns and young children are most at risk from it [28]. There has been a notable decrease in private investment and innovation into antibiotic development, which may decrease opportunities for developing new antibiotics.

Due to high costs and low returns from research on antibiotics, pharmaceutical companies have reduced their involvement and further diminished pipeline capacity despite various organizations offering push funding [28]. This trend persists despite various organizations providing push funding incentives to stimulate antibiotic research and development. Investment in antimicrobial research and development represents a threat to global health, as the rise of antibiotic-resistant pathogens outpaces new treatment developments. Antibiotic development poses unique difficulties, including regulatory hurdles, complex scientific research efforts to identify effective compounds, and market restrictions that limit the profitability of new antibiotics. This situation becomes even more dire given that all these hurdles must be navigated before success can be realized. Furthermore, the economic model behind antibiotic development does not align adequately with the need to use these drugs wisely to minimize resistance. In contrast to medications for chronic conditions, antibiotics are generally taken only briefly and even then, only as a last resort, further diminishing profitability and reflecting societal costs such as increased healthcare expenditures and impactful public health measures in their market value.

2. Conclusion

AMR occurs and grows, not only because of a lack of scientific innovation but also due to systemic gaps that exist in policy implementation, information dissemination, and resource allocation. Reducing AMR requires taking an integrated approach that incorporates medical advances with successful implementation of stewardship programs, international cooperation and strengthening healthcare systems, particularly those found in LMICs. An approach must address both information lack and misutilisation of knowledge for an efficient global response against AMR’s rising tide.

Moreover, nations must embrace and promote the One Health approach, recognizing its interconnectivity among human, animal, and environmental health. To operationalize it on this front at national levels, countries should prioritize multisectoral action plans integrated into national healthcare strategies that include targeted, coordinated actions at multiple levels – targeting the development of local capacity-building programs, robust surveillance systems, and evidence-based policymaking initiatives. These actions need to include targeted and coordinated measures at multiple levels within the healthcare system as a whole, as well as evidence-based policymaking processes in particular, to create results at national levels.

3. Expert opinion

This editorial offers a cross-sectional discussion of AMR, exploring its historical context and multidimensional challenges it presents. It emphasizes that determining whether AMR cripples society or is simply a result of lacking information is not a binary question, but rather reflective of a complex reality in which both factors play significant roles.

Overall, there are tremendous advances and breakthroughs in developing novel antibiotics and antimicrobial materials, as well as advances in machine learning for diagnostics. However, these achievements alone cannot fully address the AMR challenge; their effective implementation into widespread action often becomes limited due to systemic issues like gaps in policy implementation, infrastructural restrictions, and funding restrictions. Our ultimate goal in this area is to establish an international response mechanism against current and emerging drug-resistant infections. This involves creating new antimicrobials, diagnostic tools and treatment strategies with equitable access and global utilization that save millions of lives, lower healthcare costs while protecting antibiotic efficacy for future generations. Therefore, I believe that fighting AMR requires addressing two main concerns: information deficit and misuse. There is an urgent need for increased dissemination of AMR-related information across scientific, medical, and public communities.

Enhancing diagnostic capacity is central to combating AMR, providing an indispensable means of detecting and tracking resistant pathogens across human, animal, and environmental sectors. Doing this requires investment in advanced diagnostic technologies integrated into One Health frameworks as well as effective utilization of diagnostic capacity that allows early detection, informed treatment decisions, and coordinated responses against challenges from AMR in diverse contexts.

An interesting area of research is positioned in fields like microbial dark matter and machine learning-based rapid antimicrobial susceptibility testing. However, to be effective and sustainable, its implementation requires robust support systems; policy frameworks, educational initiatives, and funding mechanisms must all exist for its successful execution

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.