Comparing Different Biomarkers for Gram Negative Sepsis By Metallo-beta-lactamase Producers in Intensive Care Unit

INTRODUCTION: Gram-negative sepsis is a severe condition associated with high mortality, prolonged hospital stays, and significant healthcare costs. While blood cultures remain the gold standard for diagnosis, their extended processing times and susceptibility to contamination highlight the need for faster diagnostic tools.(1) Biomarkers like procalcitonin (PCT), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and lactate have demonstrated potential in assessing sepsis severity and prognosis.(2) Recent research emphasizes the utility of PCT and CRP for early sepsis detection, while NLR shows promise in pathogen differentiation, though its clinical application remains debated.(3) Emerging biomarkers such as ProADM, a stable fragment of adrenomedullin with roles in immune regulation and vasodilation, show promise for risk assessment in severe infections, including MBL gram-negative sepsis.(1) OBJECTIVES: Primary objective-1) Comparing different biomarkers- Procalcitonin (PCT), CRP, NLR, lactate and Proadrenomedullin(Pro-ADM) levels in gram negative sepsis between survivors and non-survivors. Secondary objective-1) Establishing cutoff of new biomarker -Proadrenomedullin in gram negative by Metallo-beta lactamase (MBL) producers. MATERIALS AND METHODS: The study was carried out at the Adult intensive care unit of a tertiary care hospital with the objective of comparing different biomarkers- Procalcitonin (PCT), CRP, NLR, lactate and Proadrenomedullin(Pro-ADM) levels between survivors and non-survivors with sepsis caused by Metallo-beta-lactamase producing organisms. It was a prospective trial lasting 12 months. Patients over 18 years old with culture-proven MBL gram-negative sepsis were enrolled after obtaining informed consent. Bacterial isolates were identified using MALDI Biotyper or VITEK 2. Proadrenomedullin levels were assessed using ELISA to determine their prognostic value alongside other biomarkers such as PCT, NLR, lactate, CRP. Comprehensive clinical data, including demographics, comorbidities, and severity scores like SOFA and APACHE II, were collected within 24 hours of sepsis diagnosis. Different biomarkers were compared. RESULTS: The study evaluated the discriminatory power and clinical relevance of biomarkers, highlighting ProADM's exceptional performance (AUC = 0.854) in prognosticating patient outcomes with a cutoff value of 1.75 nmol/L. ProADM demonstrated the highest discriminatory ability, followed by LACTATE (AUC = 0.807), CRP (AUC = 0.754), and SERUM PCT (AUC = 0.746), all showing good to very good discriminatory power. NLR had poor performance (AUC = 0.595). ProADM also correlated positively with clinical scores: a moderate correlation with SOFA (r = 0.302, p = 0.006) and a stronger one with APACHE II (r = 0.350, p = 0.001), explaining 14.9% and 20.3% of their variances, respectively. Both correlations were statistically significant, indicating the potential of ProADM to reflect disease severity. Overall, ProADM proved to be a reliable biomarker for outcome prediction and disease severity assessment. CONCLUSION: The study found significant differences in biomarker levels (CRP, PCT, NLR, Lactate, and ProADM) between survivors and non-survivors, highlighting their potential as prognostic tools. ProADM stood out with an AUC of 0.854, demonstrating very good discriminatory power for predicting patient outcomes using a cutoff value of 1.75 nmol/L. This establishes ProADM's reliability in prognostic assessments compared to other biomarkers in gram negative sepsis by MBL producers.