Passive local immunotherapy of experimental staphylococcal pneumonia with human intravenous immunoglobulin.

Abstract

Staphylococcus aureus remains a life-threatening agent of nosocomial pneumonia in immunocompromised patients. The increasing incidence of strains exhibiting wide-spectrum resistance to antibiotics, such as methicillin-resistant S. aureus (MRSA), requires new therapeutic strategies. There is renewed interest in passive immunization with human plasma-derived immunoglobulins (IVIG) as antiinfective agents. The efficacy of IVIG was tested in an experimental model of staphylococcal pneumonia, using both an MRSA clinical isolate and reference strain Cowan III, in mice immunosuppressed with cyclophosphamide. Efficient antistaphylococcal activities were obtained with IVIG administered intravenously or intranasally. IVIG saturated with protein A or its F(ab')2 fragments were as efficient as intact IVIG, suggesting that protection did not require opsonization through IgG Fc-phagocyte Fc gamma-receptor interactions. Thus, topical administration of IVIG may replace a local antibody response to S. aureus in an immunocompromised host and may be useful in prophylaxis and treatment of nosocomial S. aureus pneumonia.