Clinical trial NCT02798497: Panton Valentine Leucocidin
Official title: Panton Valentine Leucocidin : Independent Severity Factor of Staphylococcus Aureus Pneumonias
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Staphylococcus Aureus Pneumonias
Keywords: PVL
Pneumonias
Staphylococcus aureus
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2016-06-14
Enrollment: 234
Sex: ALL
Minimum age (years): 2
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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)


Eligibility criteria: 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

Primary outcomes:
measure: The survival of the patients according to the character PVL+ or PVL- of the isolated Staphylococcus aureus strains
timeFrame: After hospitalisation, an average of 21 days
Secondary outcomes:
measure: Gravity Scores : Composite measure between the IGS2 and SOFA scores for an adult and between PIM2 and PLEOD scores for a child
timeFrame: At admission at Reanimation Unit or ICU, at 24 h after admission and 7 days after admission
measure: length of stay in Reanimation and ICU
timeFrame: number of days in Reanimation and ICU
measure: length of stay in hospitalization
timeFrame: After hospitalisation, an average of 21 days
measure: 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)
timeFrame: at maximum 6 days after Sampling of blood and of serum
Other outcomes:
Locations:
city: Bron
country: France
facility: Centre National de Références des Staphylocoques Centre de Biologie et Pathologie Est 59 bd Pinel
Study officials:
References: