Staphylococcus Aureus Pneumonias clinical trials

Panton Valentine Leucocidin

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)