fortimicin-a-sulfate and Escherichia-coli-Infections

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.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Escherichia coli Infections; gamma-Globulins; Injections, Intravenous; Male; Mice; Pseudomonas Infections