Given the urgency due to the rapid emergence of multidrug-resistant (MDR) bacteria, bacteriophages (phages), which are viruses that specifically target and kill bacteria, are rising as a potential alternative to antibiotics. In recent years, researchers have begun to elucidate the safety aspects of phage therapy with the aim of ensuring safe and effective clinical applications. While phage therapy has generally been demonstrated to be safe and tolerable among animals and humans, the current research on phage safety monitoring lacks sufficient and consistent data. This emphasizes the critical need for a standardized phage safety assessment to ensure a more reliable evaluation of its safety profile. Therefore, this review aims to bridge the knowledge gap concerning phage safety for treating MDR bacterial infections by covering various aspects involving phage applications, including phage preparation, administration, and the implications for human health and the environment.

(https://www.frontiersin.org/research-topics/70036/advances-in-combatingantimicrobial-resistance-focus-on-diagnosis-therapy-and-prevention)The Escalating Threat of Antimicrobial Resistance: Global and ICU Epidemiology Antimicrobial resistance (AMR) has emerged as one of the most pressing public health threats of the 21 st century. The World Health Organization (WHO) has projected that without effective interventions, AMR could claim 10 million lives annually by 2050, surpassing cancer as a leading cause of death and imposing a cumulative economic burden of $100 trillion globally (1). The clinical landscape of AMR is particularly dire in intensive care units (ICUs), where the convergence of critically ill patients, extensive use of invasive devices, and high selective pressure from broad-spectrum antibiotics creates an ideal environment for the emergence and dissemination of multidrug-resistant organisms (MDROs) and carbapenemresistant organisms (CROs) (2,3).Infections caused by carbapenem-resistant Enterobacteriaceae (CRE), carbapenemresistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and vancomycin-resistant Enterococci (VRE) are associated with devastating clinical outcomes (4,5). A systematic analysis from the GBD 2021 Antimicrobial Resistance Collaborators revealed that bacterial AMR directly caused 1.14 million deaths in 2021 and was associated with 4.71 million deaths globally (1). In ICU settings, patients with CRO infections experience prolonged mechanical ventilation, extended ICU and hospital stay (often exceeding 20-30 days), exorbitant healthcare costs (2-3 times higher than susceptible infections), and mortality rates ranging from 40% to over 60% for CRE and CRAB infections (6)(7)(8).The health economic burden is also staggering. A recent multicenter study across 10 countries estimated that the excess cost per CRO infection ranges from $20,000 to $120,000, driven by the need for combined use of broad-spectrum antibiotics, prolonged use of extracorporeal life support devices, enhanced infection control measures, and prolonged rehabilitation (9). Moreover, the erosion of last-line antibiotics has forced clinicians to rely on older, more toxic agents such as colistin and tigecycline, further compromising patient outcomes. This Research Topic, Advances in Combating Antimicrobial Resistance: Focus on Diagnosis, Therapy, and Prevention, brings together 19 articles from dozens of submissions that address this multifaceted crisis across three interdependent pillars. The contributions herein collectively illuminate a transition from reactive, empiric management to proactive, precisionbased countermeasures.A fundamental obstacle in AMR management has been the reliance on traditional culturebased methods, which require 48-72 hours for pathogen identification and an additional 24-48 hours for antimicrobial susceptibility testing (AST). This delay forces clinicians to initiate empiric broad-spectrum therapy, inadvertently driving further resistance. In response, rapid diagnostic tests (RDTs) have revolutionized the field, enabling same-day pathogen identification and resistance gene detection directly from clinical specimens. Meanwhile, the process of blood culture is constantly being improved to shorten turn around time (TAT) (10,11).Several articles in this Research Topic showcase diagnostic innovations. Yu and colleagues developed a deep learning algorithm based on endoscopic features for rapid Helicobacter pylori infection status assessment, reducing reliance on multiple biopsies and culture confirmation. Beyond molecular panels, metagenomic next-generation sequencing (mNGS) and CRISPR-based assays represent the next frontier. mNGS enables unbiased detection of virtually almost all pathogens in a single test, proving invaluable for culture-negative infections, unexpected or fastidious pathogens, and polymicrobial communities (12,13). CRISPR-based diagnostics offer rapid, low-cost, point-of-care detection with high specificity. The application of these advanced diagnostics is moving us from educated guesswork to precise pathogen identification, forming the bedrock of modern antimicrobial stewardship. After nearly a decade of clinical application, mNGS has demonstrated its advantages over traditional detection methods in the rapid and accurate identification of pathogens. In the future, it will be further localized and efforts will be made to build multi-disciplinary teams (MDT) for the treatment of infections. Together, they will work to accurately interpret relevant reports, contributing to improved patient outcomes.Parallel to rapid phenotypic profiling, understanding the spatial architecture of polymicrobial infections is critical, as standard diagnostic cultures often disrupt complex microbial communities. In this context, ribosomal fluorescence in situ hybridization (FISH) serves as an indispensable tool for the direct, culture-independent visualization of bacterial biofilms within host tissues. As pioneered by Swidsinski and colleagues, the deployment of sequence-specific fluorescent oligonucleotide probes enables the identification of structured, pathogen-specific consortia that otherwise evade conventional mono-infectious diagnostic paradigms (14). By combining strict taxonomic identification with exact morphological localization, FISH-based diagnostic frameworks bypass the limitations of routine microbiology, offering crucial insights into biofilm-mediated resistance and guiding targeted, localized therapeutic interventions.Confronted with pan-resistant bacteria, replenishing the therapeutic pipeline is an urgent clinical necessity. This Research Topic presents real-world evidence on both established and emerging agents, as well as non-antibiotic strategies.β -lactam/ β -lactamase inhibitor (BLBLI) combinations, including ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-relebactam and...