Antibiotics are bioactive compounds capable of inhibiting bacterial growth or causing cell death through mechanisms such as disruption of cell wall or membrane integrity, inhibition of protein or nucleic acid synthesis, and selective toxicity toward microbial targets [1]. However, the widespread and often inappropriate use of these agents has intensified selective pressure on microorganisms, enabling them to develop antimicrobial resistance (AMR), defined as the capacity to survive and proliferate despite exposure to drugs that were previously effective [2]. Today, AMR poses a clear and present danger to global public health, threatening to roll back a century of medical advancements [3].

The molecular strategies underlying AMR are both varied and highly effective. Bacteria employ defenses such as producing enzymes to neutralize antibiotics, altering cell walls to limit drug entry, modifying molecular targets or developing alternative metabolic routes [1,2]. Through these strategies, resistant pathogens are able to persist and circulate not only within hospitals but across communities, making infectious diseases increasingly difficult to manage.

Resistance often begins with a spontaneous genetic mutation, which may become dominant within pathogen populations after the introduction of new antimicrobial agents, although this timeline varies across species and drugs [4]. Evolutionary pressure for resistance is amplified in environments where microbes are exposed to low, non-lethal concentrations of antibiotics, a common scenario in agricultural areas, wastewater treatment plants, and natural aquatic systems [3,5]. In clinic settings, this process is further accelerated by inappropriate prescribing, incomplete treatment courses, and the circulation of substandard medicines [2,3]. This interaction among human, animal, and environmental determinants highlights the necessity of a One Health approach to address antimicrobial resistance effectively [6,7].

Recognizing this growing threat, the World Health Organization (WHO) established its Bacterial Priority Pathogens List (BPPL), which ranks pathogens according to their risk to human health [8]. Among these, the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) are notable for causing severe healthcare-associated infections and for their capacity to acquire and disseminate resistance genes [9–11]. These organisms pose a particular threat to vulnerable patient populations.

Although ESKAPE pathogens have long been recognized as major clinical challenges, there is increasing evidence that they are widely distributed beyond hospital settings, including in soil [12], food products [13], and aquatic environments such as rivers [14], drinking water sources [15] and sewage systems [13,16]. Aquatic environments, in particular, act as important reservoirs and transmission pathways for AMR, as they continuously receive inputs from wastewater effluent, agricultural runoff, agriculture runoff, and animal waste, facilitating the persistence and spread of resistant bacteria [13,17].

Because human, animal and environmental health are intrinsically interconnected, a One Health framework is essential for a comprehensive understanding of AMR. Within this context, identifying environmental reservoirs and comparing resistance patterns across ecological compartments are critical for understanding transmission pathways [18,19].

Accordingly, this systematic review and meta-analysis aimed to evaluate the prevalence of AMR in ESKAPE pathogens from water and wastewater and to compare these estimates with resistance patterns observed in clinical isolates.