High-dose intravenous immune globulin impairs antibacterial activity of antibiotics

In an effort to examine further whether passive immunotherapy is a useful adjunct to antimicrobial therapy for neonatal group B streptococcal disease, we evaluated human intravenous immune globulin and penicillin G, alone and in combination, for their therapeutic efficacy against experimental severe group B streptococcal infection in newborn rats. Infected rats received either immunoglobulin (2 gm/kg) intraperitoneally, penicillin G (dosage varied), or a combination of the two. All animals that received immunoglobulin alone died. The mortality rate of animals treated with penicillin G alone was 51%. In contrast, therapy with combined penicillin G and immunoglobulin resulted in a significantly greater mortality rate (88%). Similar detrimental effects were also observed when human immunoglobulin (2 gm/kg) was given in conjunction with ceftriaxone (mortality rates of 95.7% for ceftriaxone and immunoglobulin versus 56.5% for ceftriaxone alone). However, a smaller dose of immunoglobulin (0.5 gm/kg) did not result in the greater mortality rate. Moreover, antibiotic-mediated bacterial killing was impaired in vitro and in vivo by a large dose of immunoglobulin but not by a smaller dose. These findings suggest that large doses of human immunoglobulin may be disadvantageous to the bacterial activity of penicillin G and ceftriaxone against group B streptococcal disease. Additional studies are needed to elucidate further the mechanisms responsible for this dose-dependent adverse effect of human immunoglobulins.