Oral ciprofloxacin and a monoclonal antibody to lipopolysaccharide protect leukopenic rats from lethal infection with Pseudomonas aeruginosa.
To study the treatment of infection with Pseudomonas aeruginosa, a leukopenic rat model was developed that closely mimics the pathogenesis of Pseudomonas infection in man. This model achieved approximately 90% mortality within 10 d of infection. Pseudomonas organisms were inconsistently shed from the feces despite gastrointestinal colonization (9 fecal v. 23 cecal cultures positive for challenge strain in 28 rats). Treatment of rats with oral ciprofloxacin at 40 mg/kg afforded complete protection. A suboptimal dose of ciprofloxacin (20 mg/kg), achieving peak levels of 0.31 micrograms/mL in serum and 26.3 micrograms/mL in stool, resulted in survival of 8 (40%) of 20 rats. Intraperitoneal administration of a monoclonal antibody directed at the lipopolysaccharide of the challenge strain of Pseudomonas resulted in survival of 5 rats (26%). The combination of the two increased the survival to 75% (15 of 20, P less than 0.05 compared to either treatment alone). Thus, the combination of suboptimal doses of ciprofloxacin and a monoclonal antibody appears to protect leukopenic rats from lethal infection better than either treatment alone.
Collins
H H
HH
Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Cross
A S
AS
Dobek
A
A
Opal
S M
SM
McClain
J B
JB
Sadoff
J C
JC
D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007116:Immunization, Passive; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D011552:Pseudomonas Infections / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D002939:Ciprofloxacin; D003520:Cyclophosphamide