Legionella
Conditions
Brief summary
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.
Interventions
OTHERSkin biopsy for genetic analyze
It will be offered to a subgroup of adult patients carrying genetic markers predisposing to the severity of the LD infection, a skin biopsy in order to realize genetic analyses. This visit will be conducted once the results of genetic markers obtained (between 30 and 36 months), a specific consent will be required to patients. The skin biopsy will be performed according to the Clinical Department use.
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Adult patients with medical and biological signs of legionnaires' disease. * Pediatric patients regardless of age but with a minimum weight of 7.5 kg with medical and biological signs of legionnaires' disease. * Patient and/or his/her legal representative have reviewed the patient information/informed consent form and have given written informed consent.
Exclusion criteria
* None Legionella pneumophila Legionnaires' disease. * Patients for whom respiratory secretions can't be obtained. * Cases diagnosed only by serology. * Outpatients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Legionnaire's disease severity measured by SOFA/PELOD score | At Hospital Output, on average 1 Day | No other specific timeframe could be provided, it will depend on patients' condition. The study will evaluate correlation between the L. pneumophila load (quantify by molecular method) to the clinical outcome of the LD infection |
| Bacterial load measured by PCR | At Hospital Output, on average 1 Day | No other specific timeframe could be provided, it will depend on patients' condition. The study will evaluate correlation between the L. pneumophila load (quantify by molecular method) to the clinical outcome of the LD infection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Specific cytokine profile | Up to Day 5 | Cytokine profile will be measured at local level (pulmonary) and/ or systemic level (serum) and associated with severity |
| Genomic analyzes | At inclusion, up to 48 hours | Genomic analyzes of bacterial genes will be associated with the legionella severity |
| Pulmonary microbiota | At inclusion, up to 48 hours | Metagenomic approaches and NGS will be used to associate a specific microbiota, or changes in the severity of LD infection |
Countries
France
Contacts
Primary ContactGérard LINA, MD PhD
Outcome results
None listed