Panton Valentine Leucocidin (PVL)

Panton Valentine Leucocidin : Independent Severity Factor of Staphylococcus Aureus Pneumonias

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)

Study Overview

• Status: Completed
• Conditions: Staphylococcus Aureus Pneumonias
• Intervention / Treatment: Other: Serum and Blood samples

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Centre National de Références des Staphylocoques Centre de Biologie et Pathologie Est 59 bd Pinel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: staphylococcus aureus PVL-; patients with staphylococcus aureus PVL-	Other: Serum and Blood samples
Other: staphylococcus aureus PVL+; patients with staphylococcus aureus PVL+	Other: Serum and Blood samples

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2011
• Primary Completion (Actual): December 21, 2016
• Study Completion (Actual): December 21, 2016

Study Registration Dates

• First Submitted: May 27, 2016
• First Submitted That Met QC Criteria: June 8, 2016
• First Posted (Estimate): June 14, 2016

Study Record Updates

• Last Update Posted (Actual): March 13, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Staphylococcus aureus; PVL; Pneumonias
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Pneumonia; Staphylococcal Infections; Pneumonia, Staphylococcal
• Other Study ID Numbers: 2010.625