Combination
therapy of
antibiotics and human intravenous gamma
immunoglobulin (
IgG) prepared for intravenous use is widely applied to control severe
infectious diseases. To evaluate the antimicrobial activity of
astromicin (ASTM,
Fortimicin), the combination effect of ASTM with
IgG was investigated in vitro and in mice with experimental
infection (i.p.) with Pseudomonas aeruginosa BMH No. 1.
Sulfonated IgG (
Venilon, VL), and
plasmin-treated
IgG (
Venoglobulin, VG) were administered (i.v., 42 mg/kg) 90 minutes before the
infection, and ASTM was administered (s.c.) 60 minutes after the
infection. Polyethyleneglycol-treated
IgG (
Venoglobulin-I, VG-I) was administered (i.v., 42 mg/kg) 90 minutes before or 60 minutes after the
infection. ED50 of ASTM alone and that of combination with VL were 31.0 mg/kg and 24.2 mg/kg, respectively. ED50 of ASTM alone and that of combination with VG were 38.9 mg/kg and 15.5 mg/kg, respectively (P less than 0.05). When VG-I was administered prophylactically, ED50 of ASTM alone and that of combination were 51.5 mg/kg and 13.6 mg/kg, respectively (P less than 0.05). When VG-I was administered simultaneously with ASTM at 60 minutes after the
infection, ED50 of ASTM alone and that of combination were 28.5 mg/kg and 15.5 mg/kg, respectively (P less than 0.05). Prophylactic effect of VG-I in immunosuppressed mice treated with
cyclophosphamide (250 mg/kg, i.p., 4 days before
infection) was also examined. ED50 of ASTM alone and that of combination were 126.1 mg/kg and 46.1 mg/kg, respectively (P less than 0.05). VG-I also enhanced in vitro synergistic bactericidal activity of ASTM and fresh mouse serum.