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1.  Presence of Genes Encoding Panton-Valentine Leukocidin Is Not the Primary Determinant of Outcome in Patients with Hospital-Acquired Pneumonia Due to Staphylococcus aureus 
Journal of Clinical Microbiology  2012;50(3):848-856.
The impact of Panton-Valentine leukocidin (PVL) on the outcome in Staphylococcus aureus pneumonia is controversial. We genotyped S. aureus isolates from patients with hospital-acquired pneumonia (HAP) enrolled in two registrational multinational clinical trials for the genetic elements carrying pvl and 30 other virulence genes. A total of 287 isolates (173 methicillin-resistant S. aureus [MRSA] and 114 methicillin-susceptible S. aureus [MSSA] isolates) from patients from 127 centers in 34 countries for whom clinical outcomes of cure or failure were available underwent genotyping. Of these, pvl was detected by PCR and its product confirmed in 23 isolates (8.0%) (MRSA, 18/173 isolates [10.4%]; MSSA, 5/114 isolates [4.4%]). The presence of pvl was not associated with a higher risk for clinical failure (4/23 [17.4%] versus 48/264 [18.2%]; P = 1.00) or mortality. These findings persisted after adjustment for multiple potential confounding variables. No significant associations between clinical outcome and (i) presence of any of the 30 other virulence genes tested, (ii) presence of specific bacterial clone, (iii) levels of alpha-hemolysin, or (iv) delta-hemolysin production were identified. This study suggests that neither pvl presence nor in vitro level of alpha-hemolysin production is the primary determinant of outcome among patients with HAP caused by S. aureus.
doi:10.1128/JCM.06219-11
PMCID: PMC3295120  PMID: 22205797
2.  Presence of Genes Encoding the Panton-Valentine Leukocidin Exotoxin Is Not the Primary Determinant of Outcome in Patients with Complicated Skin and Skin Structure Infections Due to Methicillin-Resistant Staphylococcus aureus: Results of a Multinational Trialâ–¿  
Journal of Clinical Microbiology  2009;47(12):3952-3957.
The role of Panton-Valentine leukocidin (PVL) in determining the severity and outcome of complicated skin and skin structure infections (cSSSI) caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) is controversial. We evaluated potential associations between clinical outcome and PVL status by using MRSA isolates from patients enrolled in two large, multinational phase three clinical trials assessing telavancin for the treatment of cSSSI (the ATLAS program). MRSA isolates from microbiologically evaluable patients were genotyped by pulsed-field gel electrophoresis (PFGE) and PCR for pvl and 31 other putative virulence determinants. A single baseline pathogen of MRSA was isolated from 522 microbiologically evaluable patients (25.1%) among 2,079 randomized patients. Of these MRSA isolates, 83.2% (432/519) exhibited the USA300 PFGE genotype and 89.1% (465/522) were pvl positive. Patients with pvl-positive MRSA were more likely than those with pvl-negative MRSA to be young, to be North American, and to present with major abscesses (P < 0.001 for each). Patients were significantly more likely to be cured if they were infected with pvl-positive MRSA than if they were infected with pvl-negative MRSA (91.6% versus 80.7%; P = 0.015). This observation remained statistically significant after adjustment for presence of abscess, fever, or leukocytosis; infection size; diabetes; patient age; and study medication received. The fnbA, cna, sdrC, map-eap, sed, seg, sei, sej, SCCmec type IV, and agr group II genes were also associated with clinical response (P < 0.05). This contemporary, international study demonstrates that pvl was not the primary determinant of outcome in patients with MRSA cSSSI.
doi:10.1128/JCM.01643-09
PMCID: PMC2786648  PMID: 19846653

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