title: Panton-Valentine leukocidin is not the primary determinant of outcome for Staphylococcus aureus skin infections: evaluation from the CANVAS studies.
abstract: The impact of Panton-Valentine leukocidin (PVL) on the severity of complicated skin and skin structure infections (cSSSI) caused by Staphylococcus aureus is controversial. We evaluated potential associations between clinical outcome and PVL presence in both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) isolates from patients enrolled in two large, multinational phase three clinical trials assessing ceftaroline fosamil for the treatment of cSSSI (the CANVAS 1 and 2 programs). Isolates from all microbiologically evaluable patients with monomicrobial MRSA or MSSA infections (n = 473) were genotyped by PCR for pvl and underwent pulsed-field gel electrophoresis (PFGE). Genes encoding pvl were present in 266/473 (56.2%) isolates. Infections caused by pvl-positive S. aureus were associated with younger patient age, North American acquisition, and presence of major abscesses (P<0.001 for each). Cure rates of patients infected with pvl-positive and pvl-negative S. aureus were similar overall (93.6% versus 92.8%; P = 0.72), and within MRSA-infected (94.5% vs. 93.1%; P = 0.67) and MSSA-infected patients (92.2% vs. 92.7%; P = 1.00). This finding persisted after adjustment for multiple patient characteristics. Outcomes were also similar when USA300 PVL+ and non-USA300 PVL+ infections were compared. The results of this contemporary, international study suggest that pvl presence was not the primary determinant of outcome in patients with cSSSI due to either MRSA or MSSA.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Amy
authors.initials: A
authors.lastname: Tong
authors.forename: Steven Y C
authors.initials: SY
authors.lastname: Tong
authors.forename: Yurong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Supaporn
authors.initials: S
authors.lastname: Lamlertthon
authors.forename: Batu K
authors.initials: BK
authors.lastname: Sharma-Kuinkel
authors.forename: Thomas
authors.initials: T
authors.lastname: Rude
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Ahn
authors.forename: Felicia
authors.initials: F
authors.lastname: Ruffin
authors.forename: Lily
authors.initials: L
authors.lastname: Llorens
authors.forename: Ganesh
authors.initials: G
authors.lastname: Tamarana
authors.forename: Donald
authors.initials: D
authors.lastname: Biek
authors.forename: Ian
authors.initials: I
authors.lastname: Critchley
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
mesh_terms: D000367:Age Factors; D001398:Aztreonam; D001427:Bacterial Toxins / Q000145:classification / Q000235:genetics / Q000633:toxicity*; D002511:Cephalosporins / Q000627:therapeutic use; D016521:Electrophoresis, Gel, Pulsed-Field; D005098:Exotoxins / Q000145:classification / Q000235:genetics / Q000633:toxicity*; D005260:Female; D005838:Genotype; D006801:Humans; D007956:Leukocidins / Q000145:classification / Q000235:genetics / Q000633:toxicity*; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D016133:Polymerase Chain Reaction; D013207:Staphylococcal Skin Infections / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology*; D013211:Staphylococcus aureus; D016896:Treatment Outcome; D014640:Vancomycin; D000097583:Ceftaroline
chemical_list: D001398:Aztreonam; D001427:Bacterial Toxins; D002511:Cephalosporins; D005098:Exotoxins; D007956:Leukocidins; D014640:Vancomycin; D000097583:Ceftaroline; C078284:Panton-Valentine leukocidin