Research ArticleInfectious Disease

IVIG-mediated protection against necrotizing pneumonia caused by MRSA

Science Translational Medicine  21 Sep 2016:
Vol. 8, Issue 357, pp. 357ra124
DOI: 10.1126/scitranslmed.aag1153

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Stemming the tide of MRSA-induced pneumonia

Controversies persist about the use of human intravenous immunoglobulin (IVIG) as an adjunctive treatment for severe Staphylococcus aureus pneumonia because empirical evidence supporting its use is lacking. Diep and colleagues now show that, of the myriad antibodies contained in IVIG, only two specific antibodies that neutralize the toxic effects of α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL) are necessary and sufficient to confer protection against necrotizing pneumonia caused by MRSA in a rabbit model. Preexposure prophylaxis with IVIG, or postexposure treatment with IVIG in combination with either vancomycin or linezolid, improved survival outcomes in this preclinical animal model.

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.

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