Panton-Valentine leucocidin and pneumonia

Abstract

Laura Shallcross and colleagues con cluded on the basis of their meta-analyses that individuals with pneumonia were less likely to be infected with a PantonValentine leucocidin (PVL)-positive Staphylococcus aureus strain than are those with skin and soft-tissue infection. While PVL-positive strain might have a lesser propensity to cause pneumonia compared with skin and soft-tissue infection, these meta-analyses cannot be used to make any inference regarding whether or not PVL contributes to the pathogenesis and outcomes of pneumonia. Such inference could be made on the basis of comparison of outcomes in patients with PVLpositive pneumonia versus those with PVL-negative pneumonia. However, Shallcross and colleagues did not do a meta-analysis on outcomes of PVL-positive and PVL-negative pneu monia, but instead provide qualitative summary of pneumonia outcomes from seven studies that used diff erent study designs and cannot be combined. Gillet and colleagues’ study addressing this issue was unfortunately excluded from their systematic review. Gillet and colleagues’ study showed that median survival was 4 days in patients with PVL-positive pneumonia compared with 25 days in patients with PVL-negative pneumonia, although overall mortality rates were not different between groups at 60 days after hospital admission. The rapidly fatal course of infection caused by the PVL-positive strains was associated with acute respiratory distress syndrome and characterised by severe hypoxaemia, leucopenia, haemoptysis, alveolar haemorrhage, and necrosis. An animal model is needed to investi gate molecular mechanisms by which PVL induces the rapidly fatal course of haemorrhagic necrotising pneumonia. In this regard, Shallcross and colleagues’ review failed to identify another study that elucidated mechanisms by which PVL rapidly induces severe hypoxaemia, leucopenia, lung necrosis, pulmonary oedema, alveolar haemorrhage, haemoptysis, and death in a rabbit model of necrotising pneumonia. This rabbit model showed that PVL causes lung infl ammation b y activating and recruiting neutrophils into the lungs and then lysing them to release granule enzymes and reactive oxygen metabolites that damage the lungs. In contrast with the fact that rodent and monkey neutrophils are resistant to cytotoxic eff ects of PVL, the similar susceptibilities of rabbit and human neutrophils to PVL indicate that the rabbit model of necrotising pneumonia could be used for preclinical development and evaluation of anti-PVL therapeutic approaches. Ultimately, the question of whether or not PVL has a role in disease severity could be settled by a clinical trial testing effi cacy of anti-PVL therapy (eg, specifi c monoclonal antibody that neutralises PVL) in protecting against rapidly progressive necrotising pneumonia in human beings.