Editorial: Infections in the Intensive Care Unit, Volume III

Cheng Zhu¹Bin Lin²Zhongheng Zhang^3*Yuetian Yu^4*

• ¹Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
• ²Changxing County People's Hospital, Huzhou, China
• ³Zhejiang University School of Medicine Sir Run Run Shaw Hospital Department of Respiratory and Critical Care Medicine, Hangzhou, China
• ⁴Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

Severe infections and sepsis remain the most critical challenges in the field of intensive care medicine. Given their high incidence and mortality rates, they have garnered widespread global attention. The "5 Facts and 5 Actions" initiative launched on World Sepsis Day 2025 once again emphasized the need to further enhance awareness of sepsis and mobilize all medical resources to improve patient outcomes. Since 2023, our team has been preparing a special issue on "Infections in the ICU," aiming to share advancements in both clinical and basic research in this field, with the goal of transforming clinical perspectives and translating these insights into actionable practices that can improve patient prognosis (1). We are deeply honored to have completed the compilation of the third volume with your support and assistance. Ultimately, we selected 22 out of nearly 70 submissions for publication. This collection of 22 articles represents the cutting-edge research and clinical insights from experts worldwide, addressing the most pressing challenges in the management of critically ill patients with infections. The contributions herein collectively paint a picture of a field in rapid, transformative evolution, moving from reactive paradigms to proactive, personalized, and precision medicine. The intensive care unit (ICU) remains the epicenter of the most severe and lifethreatening infections. The patients within its walls are characterized by a perfect storm of vulnerability: compromised immune defenses due to underlying disease, breaches in natural anatomical barriers from invasive devices (endotracheal tubes, central venous catheters, urinary catheters), and the frequent use of broad-spectrum antibiotics. This environment is a crucible for the selection and proliferation of multidrug-resistant organisms (MDROs) (2). This Research Topic powerfully underscores the persistent and evolving threat of antimicrobial resistance (AMR). Studies within this collection detail the grim reality of infections caused by carbapenem-resistant Enterobacteriaceae (CRE), Acinetobacter baumannii, Pseudomonas aeruginosa, and vancomycin-resistant Enterococci (VRE).These pathogens are often extensively or pan-drug resistant, leaving clinicians with a dwindling arsenal of therapeutic options. The clinical consequences are starkly illustrated: prolonged mechanical ventilation (MV), extended ICU and hospital lengths of stay, exorbitant healthcare costs, and unacceptably high mortality rates.A cross-sectional survey in many countries and regions around the world has provided sobering data on the dire prognoses associated with these infections, reinforcing that AMR is not a future threat but a present-day catastrophe in ICUs globally (3). This volume serves as a critical reminder that the foundational battle against ICU infections begins with robust infection prevention and control (IPC) measures and antimicrobial stewardship (AMS), but it must be augmented by technological advancement. A central theme emerging from this collection is the paradigm shift in microbiological diagnostics. The traditional culture-based methods, with their 48-to 72-hour turnaround times, are increasingly recognized as inadequate for guiding initial, life-saving therapy in sepsis. The articles in this section herald a new era of rapid diagnostics, which is pivotal for de-escalating empiric broad-spectrum therapy and initiating targeted treatment sooner.Multiple studies explore the clinical utility of molecular and multiplex polymerase chain reaction (PCR) panels that can identify a plethora of pathogens and key resistance genes (e.g., blaKPC, blaNDM, mecA) directly from blood or respiratory samples within hours. Some research works have demonstrated how the implementation of such technology was associated with a significant reduction in time to effective therapy and a shorter duration of unnecessary anti-MRSA or anti-pseudomonal coverage.Furthermore, the horizon of diagnostics is expanding towards more comprehensive and unbiased techniques. Metagenomic next-generation sequencing (mNGS) allows for the detection of virtually all nucleic acids in a sample, proving invaluable for diagnosing culture-negative infections, uncovering unexpected or fastidious pathogens, and characterizing complex polymicrobial communities (4,5). The application of these advanced diagnostics is moving us from a state of educated guesswork to one of precise pathogen identification, forming the bedrock upon which modern antimicrobial stewardship is built. Confronted with the rise of pan-resistant bacteria, the development of novel antimicrobial agents is not just a research priority but a clinical necessity. This Research Topic features several contributions evaluating new antibiotics and alternative therapeutic strategies. Prominent among these are the newer generations of β-lactam/βlactamase inhibitor (BLBLI) combinations (e.g., ceftolozane-tazobactam, ceftazidimeavibactam, meropenem-vaborbactam). Some studies have provided real-world evidence on the efficacy and safety of these agents for treating infections caused by extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant gramnegative bacteria. These drugs represent a critical step forward, yet the rapid emergence of resistance to even these new agents, as noted in some reports, underscores the relentless adaptability of microbes.Beyond traditional antibiotics, this volume explores innovative approaches. The role of bacteriophage therapy, a long-considered but now increasingly viable option for desperate cases with untreatable infections. Similarly, the use of monoclonal antibodies and immunomodulatory agents to augment the host's immune response against specific pathogens or their toxins represents a promising adjunctive strategy, moving therapy beyond direct microbiocidal action to a more holistic support of the infected host. Recognizing that simply prescribing an appropriate antibiotic is insufficient in the critically ill, a significant portion of this Research Topic is devoted to the pharmacokinetic (PK) challenges unique to this population. The pathophysiological alterations in sepsis and critical illness-such as augmented renal clearance, capillary leak, organ dysfunction, and the use of extracorporeal circuits-lead to highly variable and unpredictable antibiotic concentrations (6). This can result in subtherapeutic exposure (leading to treatment failure and resistance emergence) or supratherapeutic levels (causing toxicity).Therapeutic Drug Monitoring (TDM) of antibiotics, particularly for agents with a narrow therapeutic index like vancomycin and aminoglycosides, has been a standard practice. However, some studies advocated for its expansion to β-lactams and other time-dependent antibiotics. Because the results clearly showed that a substantial The clinical application of this knowledge is evolving from complex laboratory assays towards point-of-care classifiers (14). Studies here explore the use of limited protein panels or even electronic health record data that can accurately assign patients to a specific subphenotype rapidly, enabling future enrichment strategies for clinical trials and, ultimately, personalized administration of biologics and immunomodulators. The 22 articles compiled in "Infections in the Intensive Care Unit -Volume III" collectively chart a course for the future of our field. That future is one where the grim reality of AMR is met not with despair but with a coordinated, technologically sophisticated counteroffensive. It is a future where rapid diagnostics illuminate the pathogen within hours, where novel antimicrobials and adjunctive therapies provide effective treatment options, and where MIPD ensures these powerful drugs are used with precision.Most excitingly, it is a future where AI acts as a powerful co-pilot, synthesizing vast datasets to predict, diagnose, and recommend, and where the biological heterogeneity of our patients is decoded through omics, allowing us to move from treating a syndromic label to treating a specific, molecularly-defined disease process.The journey ahead requires collaboration among intensivists, microbiologists, clinical pharmacists, data scientists, and translational researchers. The work presented in thisResearch Topic is a testament to the vibrant and innovative spirit of this community. By embracing and integrating these advancements, we can transform the ICU from a battleground where we are often outmaneuvered by microbes into a center of precision medicine, where every infected critically ill patient receives the uniquely tailored care they deserve.