The efficacy of intravenous immunoglobulin in combination therapy with antibiotics for severe infections

Abstract

A large-scale, multicenter randomized trial was performed to evaluate the efficacy of intravenous immunoglobulin (IVIG) in combination therapy with antibiotics for severe infections, compared with antibiotics monotherapy, as part of the reevaluation of drugs required by the Ministry of Health and Welfare. Patients whose symptoms specific for infection did not improve sufficiently after receiving broad-spectrum antibiotics for three consecutive days were randomly allocated to the MG group or control group. The antibiotics were discontinued in both groups, and imipenem/cilastatin (IPM/CS) and amikacin (AMK) were administered consecutively for seven days from the day of the allocation (day 1). In the IVIG group, IVIG 5 g/day was concomitantly given for three days starting on day 1. Efficacy was assessed mainly on the basis of the number of days required to become afebrile and for symptom eradication as end-points. The proportion of cases excluded from the efficacy evaluation was 26.1% (178/682). There were no significant imbalances between the two groups in regard to gender, age, disease category, colony- stimulating factor (CSF) usage, baseline albumin level, baseline IgG level, or time course of neutrophil counts. The proportion of patients obtaining defervescence by day 7 estimated by the Kaplan-Meier method, was 54.8% in the IVIG group and 37.2% in the control group (the generalized Wilcoxon test: p = 0.002), and the proportions of patients whose symptoms were eradicated by day 7 were 57.3% and 39.4%, respectively (the generalized Wilcoxon test: p = 0.002). The 'response rates', defined as the proportion of patients whose outcomes was assessed as 'excellent' or 'good' based on computerized objective criteria, were 61.5% (163/265) and 47.3% (113/239), respectively (χ2test: p < 0.001). Intravenous immunoglobulins are considered to be effective for severe infections when used as combination therapy with antibiotics.