Effects of a human antiflagellar monoclonal antibody in combination with antibiotics on Pseudomonas aeruginosa infection.
The in vivo activity of human immunoglobulin M monoclonal antibody IN-2A8, which is specific for flagellum type b of Pseudomonas aeruginosa, was evaluated in comparison to anti-O antigen (serotype B) MAb KO-2F2 and in combination with antibiotics. IN-2A8 showed stronger activity than KO-2F2 against subcutaneous infection in burned mice, while it was much less active against intraperitoneal infection in normal mice. In a burn infection model, IN-2A8 inhibited the increase of bacteria in skin lesions weakly and that in blood significantly, suggesting that it strongly suppressed bacterial spread to blood. The activity of IN-2A8 in combination with 10 antipseudomonal antibiotics against intraperitoneal infection was examined. Clear additive effect was observed with a combination of either carbapenem or aminoglycoside antibiotics in terms of mouse survival. The administration of an antibiotic, imipenem-cilastatin, simultaneously with or before that of IN-2A8 gave a combined effect, but the reverse order did not. The combination of IN-2A8 with imipenem-cilastatin decreased numbers of viable bacteria in the peritoneal cavity and blood and kept them low for a longer time than did either treatment alone. These results suggest that an antiflagellar monoclonal antibody would be effective against systemic infection in combination with some kinds of antibiotics.
Uezumi
I
I
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Terashima
M
M
Kohzuki
T
T
Kato
M
M
Irie
K
K
Ochi
H
H
Noguchi
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002056:Burns / Q000150:complications; D004195:Disease Models, Animal; D005407:Flagella / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M