Neonatal sepsis is a prevalent condition among newborns (NB), particularly those born preterm, yet a consensus definition remains elusive. The classification of the disease is based on the onset of symptoms into two categories: early-onset sepsis (EOS), defined as sepsis occurring within the first 72 h of life (with some definitions extending this to the first week), and late-onset sepsis (LOS), defined as sepsis occurring after 72 h of life [1]. Late-onset is prevalent in preterm, low-birth-weight neonates, especially those requiring prolonged hospitalization in neonatal intensive care units (NICUs). In this population, the incidence ranges from 20 % to 35 %, affecting approximately 3 million neonates annually and resulting in around 750,000 deaths worldwide [2]. The pathophysiology of neonatal sepsis is complex and involves nonspecific clinical manifestations. Complications such as multiple organ dysfunction and septic shock are primarily associated with a dysregulated inflammatory response, characterized by an imbalance between inflammatory and anti-inflammatory mediators, leading to significant tissue damage [3].

Conventional laboratory methods employed for disease screening, such as white blood cell count, immature-to-total neutrophil ratio (I/T ratio), C-reactive protein (CRP), and procalcitonin (PCT), demonstrate limited accuracy in differentiating sepsis from other inflammatory conditions. Blood culture, considered as the gold standard for etiological diagnosis, exhibits limited sensitivity, complicating the identification of pathogens [4,5]. Consequently, there has been an investigation into the use of several biomarkers to enhance the diagnosis and prognosis of neonatal sepsis. These biomarkers include cytokines (e.g., IL-6 and TNF-α) and surface markers (e.g., E-selectin and CD64). However, the current evidence remains insufficient to support their routine use in clinical practice [6].

In this context, the Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) has emerged as a promising biomarker. TREM-1 expression is upregulated by Toll-like receptor (TLR) signaling, particularly through TLR-2 and TLR-4 pathways, which enhance TREM-1 mRNA levels during microbial stimulation. Functionally, TREM-1 signals via the DAP12 (DNAX-activating protein 12) adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM). The TREM-1/DAP12 complex undergoes ITAM phosphorylation, triggering downstream cascades that activate neutrophils and monocytes. This activation leads to calcium mobilization, tyrosine phosphorylation, and the release of proinflammatory mediators including IL-8, MCP-1, and TNF-α, thereby amplifying and sustaining the TLR-driven innate immune response [[7], [8], [9]].

Besides sepsis, studies have documented its involvement in several pathological conditions, including atherosclerosis, fibrosis, Alzheimer's disease, colitis, and cancer [10]. Its activation leads to the release of the soluble fraction TREM-1 (sTREM-1), which can be detected in biological fluids such as blood and urine, even in the absence of an evident bacterial infection. Recent studies indicate that sTREM-1 shows strong diagnostic and prognostic value for LOS, with the potential to reduce patient morbidity, mortality, and overall hospital costs [11].

Based on these findings, this study aimed to evaluate the potential of TREM-1 as a biomarker in both culture-negative and culture-positive LOS caused by Gram-negative and/or Gram-positive bacteria.