Bacterial and Human Biomarkers of Prognostic Value for Severe Legionnaire's Disease

Overview

Legionnaires' disease (LD) is a relatively common pneumonia in France (1200 cases/year), 98% of cases are hospitalized and 40% require intensive care unit (ICU) admission. Risk factors that may predispose to acquisition of LD are well known. Some studies suggest that genetic factor may also enhance susceptibility to LD. The mortality rate remains high (10% to 33% in ICUs) despite improved diagnostic and therapeutic management of patients. Few prospective studies have assessed the factors associated with LD outcomes, particularly death, and most of them involved a limited number of patients. In a multicentre cohort study, the investigators recently identified risk factors associated with higher mortality such as female sex, age, ICU stay, renal failure, corticosteroid treatment and enhanced pro-inflammatory status, as assessed by higher C-reactive protein level (PMID: 22005914). Other factors are suspected but their involvement has not been formally demonstrated including a high infectious bacterial load, particular virulence of Legionella strain, and an in vivo selection of mutants resistant to prescribed antibiotics. Disease progression is highly variable from one patient to another, and usually remains unpredictable. There are no objective criteria to predict the prognosis of these patients. The clinical course of patients with LD remains difficult to predict because no predictive biomarkers have yet been characterized and the demonstration of the presence of mutants to antibiotics in vivo has never been done. The main objective of the study is to correlate the L. pneumophila load (detected by PCR) to the clinical outcome of the LD infection. Clinical severity will measured by the SOFA score (Sepsis -Related Organ Failure Assessment) or the PELOD score (Pediatric Logistic Organ Dysfunction). Secondary objectives are to identify new host and bacterial biomarkers associated with poor outcome of LD.