Pathogenesis of Staphylococcus aureus Necrotizing Pneumonia

The Role of PVL and an Influenza Coinfection

Bettina Löffler; Silke Niemann; Christina Ehrhardt; Dagmar Horn; Christian Lanckohr; Gerard Lina; Stephan Ludwig; Georg Peters


Expert Rev Anti Infect Ther. 2013;11(10):1041-1051. 

In This Article

From the First Described Cases to a Specific Disease Entity

The association of S. aureus with fatal pneumonia during influenza seasons is not a new phenomenon.[19]S. aureus superinfections probably accounted for a big part of the mortality in the influenza pandemic, such as the 1918–1919 'Spanish flu' pandemic or the 1957–1958 'Asian influenza' pandemic, when S. aureus was the commonest bacterial respiratory pathogen.[20,21] Already in 1919, clinicians reported that patients suffering from coinfections associated with S. aureus were 'extremely prostrated almost from the onset of their symptoms' and that 'the course of the disease is extremely rapid'. Furthermore, characteristic symptoms that could be indicative of necrotizing pneumonia were described, for example, leukopenia, diffuse and confluent bronchopneumonia involving wide areas of the lung in x-ray analysis, hemoptysis and massive accumulation of cocci in the sputum.[12] In the following decades, important S. aureus virulence factors, including hemolysins and leukocidins, were analyzed and associated with disease developments. The S. aureus exotoxin PVL is named by Wright[22] in 1936 on Sir Philip Noel Panton and Francis Valentine, who in 1932 described its involvement in severe soft tissue infections.[23] It became more and more clear that from the numerous S. aureus bi-component toxins that consist of type S and F proteins PVL was the most potent inducer of inflammation and dermonecrosis.[24] In 1999, Lina et al. screened a collection of clinical S. aureus isolates for PVL genes and found that PVL was not only associated with deep skin infections but also with severe forms of primary community-acquired pneumonia with hemorrhagic and necrotic features. From this epidemiological study, they drew the conclusion that PVL is a possible virulence factor associated with necrotic lesions and they also mentioned that 'typical patients had a predisposing viral infection'.[8] Three years later, in 2002, Gillet et al. described the characteristics of necrotizing pneumonia on eight retrospective and eight prospective clinical cases. Necrotizing pneumonia was defined as a separate disease entity caused by PVL-producing S. aureus strains and being distinct from pneumonia of PVL-negative strains. Because of the necrotic histopathologic appearance of the lungs, the illness was named 'S. aureus necrotizing pneumonia'.[2] In 2007, a much larger clinical study with 50 cases of necrotizing pneumonia followed analyzing disease courses, typical symptoms and risk factors predictive for lethal outcome. From this study, the authors conclude that airway bleeding and leukopenia are associated with fatal outcome.[3] In subsequent years, additional clinical reports on single cases and therapeutic approaches were published that reinforce the severe clinical courses and high mortality rates. The clinical reports of S. aureus necrotizing pneumonia that were found in PubMed in English language are summarized in Table 1.