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

Five-Year View

Up to now necrotizing pneumonia is supposed to be a rare disease. Yet, many cases of necrotizing pneumonia might not be correctly diagnosed, as the clinical course proceeds rapidly and is easily misdiagnosed as bacterial sepsis of unknown origin. The reported cases of necrotizing pneumonia are characterized by a severe clinical course often affecting young and otherwise healthy patients. If the correct diagnosis is not made at an early stage, antimicrobial therapy is often inadequate and wide lung areas are already destroyed by the action of toxins. Once this stage of the disease is reached, an effective therapy is almost impossible, accounting for the high mortality rate.

Effective and tested therapeutic agents that specifically act against PVL-mediated diseases are currently not available, but several approaches are under development. In absence of vaccine, polyvalent human immunoglobulin (IVIG) containing antibodies against PVL could be proposed since it inhibits the cytotoxicity of PVL on polymorphonuclear cells in vitro.[18] Nevertheless, work from other PVL-related infection models, for example, abscess models, suggests that antibodies to PVL might even contribute to host susceptibility to infection.[57] Furthermore, high levels of antibodies against PVL were not associated with resistance to S. aureus skin and soft tissue infection.[58] Consequently, the exact role of PVL antibodies in different types of PVL-related diseases, including necrotizing pneumonia and skin and soft tissue infections, need to be evaluated separately in appropriate model systems.

Only recently, a specific PVL-binding mechanism to human immune cells has been characterized,[34] which might open new possibilities for therapeutic strategies. As the binding of PVL to target cell membranes is the critical step for pore formation and cell destruction, intervention at this stage might be very effective to prevent disease development. Nevertheless, these therapies must be started before irreversible destruction of wide lung areas has occurred. The similar susceptibilities of rabbit and human neutrophils to PVL indicate that the rabbit model of necrotizing pneumonia could be used for preclinical development and evaluation of anti-PVL therapeutic approaches. Yet, further clinical trials testing the efficacy of novel anti-PVL therapies (for example, specific monoclonal antibody that neutralizes PVL) in protecting against rapidly progressive necrotizing pneumonia in humans will be required.

In the setting of an influenza pandemic, necrotizing pneumonia might develop into a larger and serious clinical problem. As in the last decades, PVL-positive S. aureus clones have widely spread in the USA and other areas of the world, a superinfection with a PVL-expressing S. aureus strain in influenza patients might become a frequent situation. Consequently, particularly during influenza seasons an increased rate of necrotizing pneumonia should be expected and considered as possible diagnosis.