Biomarkers define the clinical response to dexamethasone in community-acquired pneumonia

Objectives: Adjuvant dexamethasone treatment in patients with community-acquired pneumonia (CAP) can reduce length of hospital stay. Whether there are subgroups of patients that especially might benefit from corticosteroids is unknown. We hypothesized that a discrepancy between systemic inflammation and cortisol level can define a subgroup that lacks a sufficient cortisol response during CAP, and therefore particularly might benefit from corticosteroids. Methods: A secondary analysis was performed on data from hospitalized patients with CAP, randomized to a four-day course of dexamethasone (5 mg daily) or placebo. Subgroups were made based on plasma cytokine levels (interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1)) and total plasma cortisol on presentation. Intensive care unit (ICU) admission and mortality were assessed. Results: 275 Patients (131 dexamethasone, 144 placebo) were analyzed. In the subgroup of patients (n = 23) with a high cytokine response (IL-6 >= 92.5 pg/mL, IL-8 >= 14.8 pg/mL and MCP-1 >= 1154.5 pg/mL) and a discrepantly low cortisol (lowest 50%), dexamethasone treatment was associated with a significant decrease on a combined endpoint of mortality/ICU admission, as compared with placebo (0% vs. 43%, p < 0.01). In the subgroup of patients with a high cytokine response and high cortisol (n = 23), this favorable effect of dexamethasone was absent (30% vs. 39%, p: 0.67). Conclusions: In CAP patients presenting with a high pro-inflammatory cytokine response but a discrepantly low cortisol, adjuvant dexamethasone treatment was associated with a significant decrease in mortality/ICU admission. (C) 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.