Panton Valentine Leucocidin

Study Overview
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Brief Summary
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Staphylococcus aureus expresses a variety of virulence factors, including Panton Valentine leukocidin (PVL), a cytotoxin. PVL is specifically associated with primary skin and soft-tissue infections and severe necrotizing pneumonia (Gillet et al. Lancet, 2002;359:753-9). PVL-positive S. aureus pneumonia is often preceded by influenza-like symptoms, and is mainly characterized by hemoptysis, pleural effusion, rapid onset of acute respiratory distress, leukopenia and a high fatality rate (65%) (Gillet et al. Lancet, 2002;359:753-9). Ten year after the first description of this disease and a number of controversies in the scientific literature, the question arise as to whether PVL remains an independent factor of severity in S.aureus pneumonia. In addition, numerous questions remain unanswered yet; these are: (i) which factors, including treatment regimen, are associated with favourable outcome?, (ii) what is the susceptibility toward antibiotics of strains associated with this disease ? (iii) is there any genetic susceptibility of the host to explain both the rarity, and the explosive presentation of the disease ? To address the above questions a prospective observational study at the nationwide level will be set up. All French hospitals will be invited to describe the clinical features of all new cases of S. aureus community-acquired pneumonia with severity criteria, regardless PVL production. The study will include an investigation of a possible innate immune dysfunction in collaboration with the INSERM-U550 (Génétique Humaine des Maladies Infectieuses, Faculté Necker, Paris). Hence, in addition to collecting clinical and biological data from all pneumonia cases as well as all strains of S. aureus isolated, the patients with PVL-positive pneumonia will be sampled for immune genetic studies (ORFeome sequencing and functional studied)

Official Title
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Panton Valentine Leucocidin : Independent Severity Factor of Staphylococcus Aureus Pneumonias

Conditions
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Staphylococcus Aureus Pneumonias

Intervention / Treatment
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* Other: Serum and Blood samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 2-month-old patient at minimum and weighing at least 5 kg Informed consent Subjects affiliated (or beneficiary) to a national medical insurance Presence of clinical, biological and radiological signs of pneumopathy to S. aureus whose clinical state justifies a hospitalization in a ICU or in a reanimation Presence of PVL- positive S.aureus producer (for immunogenetic study) Exclusion Criteria: Patients infected by the HIV Patients hospitalized for more than 48 hours at the time of the diagnosis of pneumonia, Patients hospitalized during the previous three months excepted outpatients

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: staphylococcus aureus PVL-<br>patients with staphylococcus aureus PVL- | Other: Serum and Blood samples<br> <br> |
| Other: staphylococcus aureus PVL+<br>patients with staphylococcus aureus PVL+ | Other: Serum and Blood samples<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The survival of the patients according to the character PVL+ or PVL- of the isolated Staphylococcus aureus strains | Percentage of alive patients after the length of stay in hospitalisation | After hospitalisation, an average of 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gravity Scores : Composite measure between the IGS2 and SOFA scores for an adult and between PIM2 and PLEOD scores for a child |  | At admission at Reanimation Unit or ICU, at 24 h after admission and 7 days after admission | 
| length of stay in Reanimation and ICU | After hospitalisation, an average of 21 days | number of days in Reanimation and ICU | 
| length of stay in hospitalization |  | After hospitalisation, an average of 21 days | 
| Number of participants with presence of a genetic predisposition of Mendelian type or polymorphic character among the patients presenting a PVL+ necrotizing pneumonia (for immunogenetic study) | genomic analysis an immunologic tests | at maximum 6 days after Sampling of blood and of serum | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PVL, Pneumonias, Staphylococcus aureus