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 Medjournal_title
Science translational medicineauthors
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 Gdoi
10.1126/scitranslmed.aag1153subject
Has Abstractpub_date
2016-09-21 00:00:00pages
357ra124issue
357eissn
1946-6234issn
1946-6242pii
8/357/357ra124journal_volume
8pub_type
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