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.

journal_name

Sci Transl Med

authors

Diep BA,Le VT,Badiou C,Le HN,Pinheiro MG,Duong AH,Wang X,Dip EC,Aguiar-Alves F,Basuino L,Marbach H,Mai TT,Sarda MN,Kajikawa O,Matute-Bello G,Tkaczyk C,Rasigade JP,Sellman BR,Chambers HF,Lina G

doi

10.1126/scitranslmed.aag1153

subject

Has Abstract

pub_date

2016-09-21 00:00:00

pages

357ra124

issue

357

eissn

1946-6234

issn

1946-6242

pii

8/357/357ra124

journal_volume

8

pub_type

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