Assessment of the efficacy of polyclonal intravenous immunoglobulin G (IVIG) against the infectivity of clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo.

The response to treatment of severe methicillin-resistant Staphylococcus aureus (MRSA) infections with the traditional antibiotics is sometimes unsatisfactory and multiple antibiotic resistance is common. Adjuvant therapy such as intravenous immunoglobulin G (IVIG) could possibly be helpful in the treatment of such infections. The effect of IVIG on the capacity of human neutrophils to phagocytose and kill MRSA was investigated in vitro using the MTT assay and measuring the production of reactive oxygen species (ROS) and nitric oxide (NO). The efficiency of IVIG in neutralizing α-hemolysin and coagulase of MRSA was also assessed. The capability of IVIG in the treatment and prevention of MRSA infections was also evaluated in a murine peritonitis model. IVIG significantly enhanced (p < 0.01) the killing of MRSA by neutrophils at all concentrations tested (0.1-5 mg/ml) by 30-80 % of control values. It significantly (p < 0.01) increased the level of NO production in a dose-dependent manner, giving up to 60 μM at 5 mg/ml. The ROS level significantly increased (p < 0.01) in the presence of IVIG. In addition, IVIG significantly reduced the hemolytic activity of MRSA 10-fold and its coagulation capabilities by 50 %. When tested in vivo, groups receiving IVIG via tail vein infusion showed no significant improvement in their survival. Only when delivered to the same site of infection did IVIG show an improvement in the survival of mice (n = 80). These results could pave the way for a better understanding of the mechanism of action of IVIG and suggest its clinical potential as an adjuvant preventive and therapeutic agent against life-threatening infections caused by MRSA and other bacteria.