**Background:** Bacterial sepsis causes an estimated 11 million deaths annually worldwide, with disproportionately high mortality in low- and middle-income countries. Early recognition is critical but remains challenging due to nonspecific presentations and suboptimal diagnostic tools. Existing scores (SIRS, qSOFA) have modest accuracy, and blood cultures are negative in over one-third of cases. Neutrophil gelatinase-associated lipocalin (NGAL), a protein released from neutrophils and epithelial cells that binds bacterial siderophores, has emerged as a potential biomarker for sepsis independent of its established role in acute kidney injury (AKI). This study aimed to evaluate whether a single plasma NGAL measurement at ED presentation can predict bacterial sepsis and to develop a composite clinical scoring tool incorporating NGAL.
**Methods:** This prospective cohort study was conducted from June 2017 to April 2018 in the ED of a 3000-bed tertiary care hospital in South India. Patients >18 years with fever and SIRS ≥2 requiring hospitalization were enrolled. Exclusion criteria included fever >2 weeks, antibiotics within 48 hours, recent hospitalization/surgery, HIV, and CKD. Plasma NGAL was collected at admission and measured via turbidimetry (Bio Porto/cobas 1800). Bacterial sepsis was defined by positive blood culture (excluding skin contaminants) or physician diagnosis confirmed by two independent reviewers, with a third senior physician resolving conflicts. Clinical and laboratory parameters were collected via a pre-designed case report form. The optimal NGAL cut-off was determined using the Youden Index from ROC analysis. A predictive scoring tool was developed using Poisson regression with robust SE on an 80:20 train-test split; risk ratios were rounded to assign integer weights. Multilevel likelihood ratios were calculated for score segments.
**Key Results:** Of 100 patients enrolled, 37 had bacterial sepsis (21 blood-culture-positive, 16 physician-diagnosed). Gram-negative sepsis predominated (86% vs. 14%), with E. coli most common (57%). Scrub typhus was the most frequent alternative diagnosis (25% of non-sepsis). The optimal plasma NGAL cut-off was 570 ng/mL, yielding an AUC of 0.69 (95% CI: 0.59–0.79), sensitivity 87%, and specificity 46%. A 100 mg/dL increase in NGAL was associated with a RR of 1.04 (95% CI: 1.01–1.06) for sepsis, unchanged after creatinine adjustment. NGAL >570 ng/mL was not significantly associated with AKI (creatinine >2 mg/dL; p=0.30), suggesting sepsis-related elevation independent of renal injury. The final NGAL sepsis screening tool assigned weighted scores: diabetes mellitus (1 point), rigors (2 points), qSOFA ≥2 (2 points), any focus of infection (3 points), and plasma NGAL ≥570 ng/mL (3 points). In the training set (n=80), the tool achieved an AUC of 0.86; in the test set (n=20), AUC was 0.76. A score <3 ruled out sepsis (interval LR 0.14 in training, 0.00 in test; sensitivity 96–100%). A score >7 was highly suggestive of sepsis in the training set (interval LR 7.78, specificity 88–100%) but less impressive in the test set (LR 3.71, only 3 patients in this category). Most patients scored 3–7, where the tool could not reliably differentiate sepsis from other causes.
**Clinical Implications:** The NGAL sepsis screening tool offers a practical, multi-component approach that outperforms plasma NGAL alone (AUC 0.69 vs. 0.86 in training). A score <3 effectively excludes bacterial sepsis, potentially reducing unnecessary antibiotic use, while a score >7 strongly supports the diagnosis and could trigger early goal-directed therapy. The tool's components are readily available in most ED settings, and a point-of-care NGAL test exists (Alere Triage®), enhancing feasibility. However, the modest performance in the intermediate score range (3–7) reflects real-world diagnostic uncertainty and underscores the need for additional testing in these patients. Limitations include small sample size, single-center design, lack of comparison with CRP/PCT, and batch-processed (not point-of-care) NGAL assays. The test set included only 20 patients, limiting precision of performance estimates. External validation in larger, multi-center prospective cohorts is essential before widespread adoption. Nonetheless, this study provides a promising, clinically grounded tool that addresses an urgent need for rapid, accurate sepsis diagnosis in resource-limited ED settings.