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

Disclosures

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

In This Article

Abstract and Introduction

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.

Introduction

Staphylococcus aureus necrotizing pneumonia is described as a highly lethal infection that mainly affects healthy children and young adults and is associated with S. aureus strains producing the pore-forming toxin Panton-Valentine leukocidin (PVL). PVL is composed of two subunits, the LukS-PV and the LukF-PV proteins encoded by the pvl genes that have been integrated into the chromosome of methicillin-sensitive (MSSA) or -resistant Staphylococcus aureus (MRSA).[1] Current clinical knowledge of necrotizing pneumonia is mainly based on a series of worldwide case reports. In general, previously healthy children or young adults initially present with influenza-like symptoms that rapidly worsen to respiratory failure and septic shock. If therapy is not started early, mortality rates are very high. Post-mortem examinations of the lung usually reveal hemorrhagic necrosis and destructions of wide lung areas.[2] PVL-associated necrotizing pneumonia can be distinguished from other forms of S. aureus-caused pneumonias, which are much more frequent. PVL-negative strains generally induce a 'classical' S. aureus pneumonia, which is less fulminant, occurs in older adults (age ≥60 years), is frequently superimposed on underlying diseases and has lower mortality rates.[2,3]S. aureus is estimated to cause 1–10% of community-acquired pneumonias and 20–50% of nosocomial pneumonias.[4]

In the last decades, there was a dramatic increase in the infection rate with community-associated methicillin-resistant S. aureus strains (CA-MRSA) that carry the genes for PVL. Particularly, the MRSA strain USA300 has widely spread in North America and also in some areas of Europe.[5] In Europe, there is a much higher genetic diversity among the CA-MRSA strains, but the predominant clone is the European ST80.[6] These CA-MRSA strains often cause a more severe disease such as deep skin infections. In the USA, the high prevalence of PVL-positive CA-MRSA is mostly responsible for necrotizing infections, whereas in Europe the majority of cases of necrotizing pneumonia are caused by PVL-positive methicillin-susceptible S. aureus strains that are as virulent as the PVL-positive CA-MRSA clones.[3,7]

Although a clear epidemiological association between PVL-positive S. aureus strains and necrotizing pneumonia has been shown,[2,3,8] some authors doubt the role of PVL in disease development, as there are conflicting results particularly from different murine infection models. They suggest that the presence of the PVL genes is not a major virulence factor and that PVL is only a marker of other more relevant virulence factors.[9–11]

The scope of this article is to review 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.

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