IVIG-mediated protection against necrotizing pneumonia caused by MRSA

• Published in: Science translational medicine Vol. 8; no. 357; p. 357ra124
• Main Authors: Diep, Binh An, Le, Vien T M, Badiou, Cedric, Le, Hoan N, Pinheiro, Marcos Gabriel, Duong, Au H, Wang, Xing, Dip, Etyene Castro, Aguiar-Alves, Fábio, Basuino, Li, Marbach, Helene, Mai, Thuy T, Sarda, Marie N, Kajikawa, Osamu, Matute-Bello, Gustavo, Tkaczyk, Christine, Rasigade, Jean-Philippe, Sellman, Bret R, Chambers, Henry F, Lina, Gerard
• Format: Journal Article
• Language: English
• Published: United States 21.09.2016
• Subjects: Acute Lung Injury - drug therapy; Acute Lung Injury - microbiology; Acute Lung Injury - pathology; Animals; Antibiotic Prophylaxis; Antibodies, Neutralizing - immunology; Bacterial Toxins - immunology; Disease Models, Animal; Exotoxins - immunology; Hemolysin Proteins - immunology; Humans; Immunoglobulins, Intravenous - therapeutic use; Leukocidins - immunology; Linezolid - pharmacology; Linezolid - therapeutic use; Methicillin-Resistant Staphylococcus aureus - immunology; Methicillin-Resistant Staphylococcus aureus - physiology; Pneumonia, Necrotizing - drug therapy; Pneumonia, Necrotizing - microbiology; Rabbits; Vancomycin - pharmacology; Vancomycin - therapeutic use
• ISSN: 1946-6242
• DOI: 10.1126/scitranslmed.aag1153

New therapeutic approaches are urgently needed to improve survival outcomes for patients with necrotizing pneumonia caused by Staphylococcus aureus One such approach is adjunctive treatment with intravenous immunoglobulin (IVIG), but clinical practice guidelines offer conflicting recommendations. In a preclinical rabbit model, prophylaxis with IVIG conferred protection against necrotizing pneumonia caused by five different epidemic strains of community-associated methicillin-resistant S. aureus (MRSA) as well as a widespread strain of hospital-associated MRSA. Treatment with IVIG, either alone or in combination with vancomycin or linezolid, improved survival outcomes in this rabbit model. Two specific IVIG antibodies that neutralized the toxic effects of α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL) conferred protection against necrotizing pneumonia in the rabbit model. This mechanism of action of IVIG was uncovered by analyzing loss-of-function mutant bacterial strains containing deletions in 17 genes encoding staphylococcal exotoxins, which revealed only Hla and PVL as having an impact on necrotizing pneumonia. These results demonstrate the potential clinical utility of IVIG in the treatment of severe pneumonia induced by S. aureus.