Efficacy of anti-endotoxin monoclonal antibody E5 alone or in combination with ciprofloxacin in neutropenic rats with Pseudomonas sepsis.
Pathogen-free rats were rendered neutropenic, given oral feedings of Pseudomonas aeruginosa 12.4.4, then monitored for fever. At the onset of fever, rats were given intravenous treatment with either anti-endotoxin monoclonal antibody (MAb) E5 or control MAb B55. Survival was significantly greater in E5- than in B55-treated animals (P < .01). Serum levels of both lipopolysaccharide and tumor necrosis factor-alpha were significantly reduced in E5- versus B55-treated rats 24 h after treatment (P < .01 and < .05, respectively). Rats were also treated with E5 or B55 in combination with a suboptimal dose of ciprofloxacin at fever onset and again 24 h later. Survival was significantly greater in ciprofloxacin-treated animals given E5 than in animals given B55 (P < .005). Posttreatment endotoxin levels were decreased in animals receiving E5 in combination with ciprofloxacin (P < .001) compared with B55-treated animals. These results indicate that therapy with anti-endotoxin MAb E5 alone or in combination with antimicrobial therapy improves survival in this bacteremic infection model of Pseudomonas sepsis.
Romulo
R L
RL
Division of Infectious Diseases, Brown University, Providence, Rhode Island.
Palardy
J E
JE
Opal
S M
SM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016470:Bacteremia / Q000150:complications / Q000628:therapy*; D002939:Ciprofloxacin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004731:Endotoxins / Q000032:analysis / Q000276:immunology*; D005260:Female; D009503:Neutropenia / Q000150:complications; D011552:Pseudomonas Infections / Q000150:complications / Q000401:mortality / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D002939:Ciprofloxacin