Longitudinal and adjusted prognostic assessment of calprotectin in Gram-negative sepsis with acute respiratory failure

ABSTRACT Sepsis caused by Gram-negative bloodstream infection is characterized by dynamic host responses, but the longitudinal and incremental prognostic value of calprotectin remains uncertain. We conducted a multicenter retrospective observational study of 82 adults with Gram-negative bloodstream infection, sepsis, and acute respiratory failure. Serum calprotectin, routine biomarkers, cytokines, and growth factors were measured at diagnosis before antibiotic therapy (T0), day 3 (T1), and day 7 (T2), and compared according to 28-day survival. Sixty-four patients survived, and 18 died. Calprotectin declined over time but remained higher in non-survivors at T0 ( P = 0.003), T1 ( P = 0.037), and T2 ( P = 0.035); its longitudinal trajectory did not differ between survivors and non-survivors ( P = 0.408). Selected routine and immune biomarkers showed nominal differences at T2, but none of the 63 secondary biomarker-by-time comparisons remained significant after false-discovery-rate correction. Sequential organ failure assessment 2 (SOFA-2) alone strongly discriminated mortality (area under the receiver operating characteristic curve [AUC], 0.897; 95% CI, 0.828–0.965) and outperformed baseline calprotectin (AUC, 0.728; DeLong P = 0.027). Baseline calprotectin remained independently associated with mortality after adjustment for age and SOFA-2 (OR, 2.07 per doubling; 95% CI, 1.14–4.20; P = 0.018), but its addition yielded only a modest, non-significant improvement in discrimination (ΔAUC, 0.023; P = 0.117). SOFA-2 was the dominant prognostic discriminator; calprotectin may provide complementary rather than standalone prognostic information and requires external validation. IMPORTANCE Gram-negative bloodstream infection accompanied by acute respiratory failure carries a substantial risk of death. In this cohort, sequential organ failure assessment 2 (SOFA-2) was the strongest early predictor of 28-day mortality. Calprotectin was higher in non-survivors from diagnosis through day 7 and remained associated with mortality after adjustment for age and SOFA-2, but adding it to the clinical model produced only a modest and statistically non-significant improvement in discrimination. Other routine and immune biomarkers showed nominal late differences that did not remain significant after false-discovery-rate correction. These findings suggest that calprotectin may complement, but should not replace, established clinical severity assessment. Larger prospective cohorts with external validation are required before calprotectin or multimarker panels can be used for clinical risk stratification.