Pathogenesis of Staphylococcus aureus necrotizing pneumonia: the role of PVL and an influenza coinfection

Abstract

Only recently necrotizing pneumonia was defined as a specific disease entity that is caused by a Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus strain and is frequently preceded by an influenza infection. Necrotizing pneumonia is characterized by a sudden onset and rapid worsening of symptoms, leukopenia, airway hemorrhages, severe respiratory failure and a high mortality rate. Despite clear epidemiological data, the function of PVL in necrotizing pneumonia has been controversially discussed due to conflicting results from different disease models. Furthermore, there are many proposed mechanisms how a viral infection could facilitate and interact with a bacterial superinfection. In this review, we summarize current data from 43 clinical cases and results from various infection models on necrotizing pneumonia. We discuss the contribution of S. aureus PVL and a preceding influenza infection and present a concept of the pathogenesis of necrotizing pneumonia.

Keywords::

• bacterial superinfection
• influenza
• lung alveolar destruction
• necrotizing pneumonia
• Staphylococcus aureus PVL

Financial & competing interest disclosure

This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) grant (HA3177/2-1 and SFB1009/B1 to G Peters and B Löffler), by a Bundesministerium für Bildung und Forschung (BMBF) grant (01KI1104 to B Löffler and C Ehrhardt). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Necrotizing pneumonia is defined as a separate disease entity that is characterized by sudden onset and rapid worsening of the symptoms, leukopenia, airway hemorrhages, severe respiratory failure, a high mortality rate and necrotic destruction of wide areas of the lung.

• • Epidemiological studies show a clear association between necrotizing pneumonia and Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus strains. Despite the clear epidemiological data, there are conflicting results on the role of PVL from different disease models that can be partly explained by the strong cell- and species-specificity of PVL.

• • PVL is a pore-forming exotoxin that rapidly activates and kills human neutrophils, monocytes and macrophages. The destructive effect of PVL is most likely caused by uncontrolled death of these immune cells that release proteases and other active compounds that are spilled in the surrounding tissue and induce tissue destruction.

• • A preceding viral infection is frequently reported and a possible causative factor for necrotizing pneumonia. A number of mechanisms of bacterial–viral interactions have been proposed. In necrotizing pneumonia, a viral-induced influx of immune cells to lung tissue could promote disease development.

• • Patients presenting with symptoms of lower respiratory tract infections that rapidly worsen to respiratory failure in combination with leukopenia should be suspected of necrotizing pneumonia. Cure of the infection has been reported particularly when therapy was started early before the patients enter into a lung destructive or septic stage.

• • The best treatment of this specific disease entity has not been clearly defined. Therapy should be performed with anti-staphylococcal therapy in combination with clindamycin. Although the mortality rate is high, patients can fully recover without further signs of pulmonary disease.

Notes