Antimicrobial Resistance in the Global Health Network: Known Unknowns and Challenges for Efficient Responses in the 21st Century

Abstract

Antimicrobial resistance (AMR) is one of the Global Health challenges of the 21st century. The inclusion of AMR on the global map parallels the scientific, technological, and organizational progress of the healthcare system and the socioeconomic changes of the last 100 years. Available knowledge about AMR has mostly come from large healthcare institutions in high-income countries and is scattered in studies across various fields, focused on patient safety (infectious diseases), transmission pathways and pathogen reservoirs (molecular epidemiology), the extent of the problem at a population level (public health), their management and cost (health economics), cultural issues (community psychology), and events associated with historical periods (history of science). However, there is little dialogue between the aspects that facilitate the development, spread, and evolution of AMR and various stakeholders (patients, clinicians, public health professionals, scientists, economic sectors, and funding agencies). This study consists of four complementary sections. The first reviews the socioeconomic factors that have contributed to building the current Global Healthcare system, the scientific framework in which AMR has traditionally been approached in such a system, and the novel scientific and organizational challenges of approaching AMR in the fourth globalization scenario. The second discusses the need to reframe AMR in the current public health and global health contexts. Given that the implementation of policies and guidelines are greatly influenced by AMR information from surveillance systems, in the third section, we review the unit of analysis ("the what" and "the who") and the indicators (the "operational units of surveillance") used in AMR and discuss the factors that affect the validity, reliability, and comparability of the information to be applied in various healthcare (primary, secondary, and tertiary), demographic, and economic contexts (local, regional, global, and inter-sectorial levels). Finally, we discuss the disparities and similarities between distinct stakeholders' objectives and the gaps and challenges of combatting AMR at various levels. In summary, this is a comprehensive but not exhaustive revision of the known unknowns about how to analyze the heterogeneities of hosts, microbes, and hospital patches, the role of surrounding ecosystems, and the challenges they represent for surveillance, antimicrobial stewardship, and infection control programs, which are the traditional cornerstones for controlling AMR in human health.

Keywords: antimicrobial resistance; antimicrobial stewardship; disease ecology; ecosystem; global health; lateral public health; metasystem; one health; social health; syndemic.

Figure 2

Challenges of AMR measurements. The validity, reliability, and comparability of the information [175,176,177,178,179,180,181,182].

Figure 2

Challenges of AMR measurements. The validity, reliability, and comparability of the information [175,176,177,178,179,180,181,182].

Figure 1

A framework for antimicrobial resistance in the healthcare network of the 21st century. A multidisciplinary approach for the analysis of AMR in a host metasystem landscape. (A) The current framework to approach health and global health challenges, which includes antimicrobial resistance (AMR) and pandemics [61]. (B) Multidisciplinary approaches to analyzing host and microbe heterogeneity and their interactions in the context of individual human health, which is influenced by intrinsic individual traits (e.g., genetics and physiology) and the exposome (exposure to environment/s, social habits, and contact with abiotic and non-abiotic entities). Individual microbial heterogeneity at sub-specific (gene, plasmid, clone) and supra-specific (microbiome) hierarchical levels is the focus of clinical microbiology and molecular epidemiology; host-microbe interactions and dynamics are analyzed by disease ecology and community ecology. (C) The WHO Health System Building Blocks framework, which was developed to promote a common understanding of the health system [112]. This is relevant for public health investments and results to feed global decision-making. (D) The Bioecological System Model of Human development. It establishes different levels (systems) of exposure to social groups [113,114]. These levels overlap those of microbial exposure. Orange-colored areas represent the influence of time in all systems (human, microbial, individual species, and institutions). Brown arrows represent connections between the various levels. Dotted boxes reflect the central targeted unit, namely humans, in (A,D); human groups in (C); and microbes and hosts in (B).