title: IVIG-mediated protection against necrotizing pneumonia caused by MRSA.
abstract: 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.
authors.affiliation: Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA. binh.diep@ucsf.edu gerard.lina@univ-lyon1.fr.
authors.forename: Binh An
authors.initials: BA
authors.lastname: Diep
authors.affiliation: Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
authors.forename: Vien T M
authors.initials: VT
authors.lastname: Le
authors.affiliation: INSERM U1111, Université Lyon 1, CNRS UMR5308, ENS Lyon, Lyon, France. Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Bron, France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Badiou
authors.affiliation: Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
authors.forename: Hoan N
authors.initials: HN
authors.lastname: Le
authors.affiliation: Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA. Pathology Program, Fluminense Federal University, Niterói, RJ, Brazil.
authors.forename: Marcos Gabriel
authors.initials: MG
authors.lastname: Pinheiro
authors.affiliation: Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
authors.forename: Au H
authors.initials: AH
authors.lastname: Duong
authors.affiliation: Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
authors.forename: Etyene Castro
authors.initials: EC
authors.lastname: Dip
authors.affiliation: Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA. Pathology Program, Fluminense Federal University, Niterói, RJ, Brazil.
authors.forename: Fábio
authors.initials: F
authors.lastname: Aguiar-Alves
authors.affiliation: Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Basuino
authors.affiliation: Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
authors.forename: Helene
authors.initials: H
authors.lastname: Marbach
authors.affiliation: Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
authors.forename: Thuy T
authors.initials: TT
authors.lastname: Mai
authors.affiliation: Laboratory of Immunology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France.
authors.forename: Marie N
authors.initials: MN
authors.lastname: Sarda
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kajikawa
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Matute-Bello
authors.affiliation: Department of Infectious Diseases, MedImmune, LLC, Gaithersburg, MD 20878, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Tkaczyk
authors.affiliation: INSERM U1111, Université Lyon 1, CNRS UMR5308, ENS Lyon, Lyon, France. Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Bron, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Rasigade
authors.affiliation: Department of Infectious Diseases, MedImmune, LLC, Gaithersburg, MD 20878, USA.
authors.forename: Bret R
authors.initials: BR
authors.lastname: Sellman
authors.affiliation: Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
authors.forename: Henry F
authors.initials: HF
authors.lastname: Chambers
authors.affiliation: INSERM U1111, Université Lyon 1, CNRS UMR5308, ENS Lyon, Lyon, France. Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Bron, France. binh.diep@ucsf.edu gerard.lina@univ-lyon1.fr.
authors.forename: Gerard
authors.initials: G
authors.lastname: Lina
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D000818:Animals; D019072:Antibiotic Prophylaxis; D057134:Antibodies, Neutralizing / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D004195:Disease Models, Animal; D005098:Exotoxins / Q000276:immunology; D006460:Hemolysin Proteins / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007956:Leukocidins / Q000276:immunology; D000069349:Linezolid / Q000494:pharmacology / Q000627:therapeutic use; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology / Q000502:physiology*; D000071067:Pneumonia, Necrotizing / Q000188:drug therapy* / Q000382:microbiology*; D011817:Rabbits; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D057134:Antibodies, Neutralizing; D001427:Bacterial Toxins; D005098:Exotoxins; D006460:Hemolysin Proteins; D016756:Immunoglobulins, Intravenous; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; C021091:staphylococcal alpha-toxin; D014640:Vancomycin; D000069349:Linezolid