Effect of anti-CD14 monoclonal antibody on clearance of Escherichia coli bacteremia and endotoxemia.
OBJECTIVE
To determine the effects of an anti-CD14 monoclonal antibody on the clearance of a bacteremic Escherichia coli challenge in the presence or absence of antimicrobial agents.


METHODS
Prospective randomized animal study.


METHODS
University-affiliated research laboratory.


METHODS
New Zealand White rabbits weighing 1.5-2.5 kg.


METHODS
Animals were pretreated with either an anti-lapine CD14 monoclonal antibody (immunoglobulin G2a, 5 mg/kg intravenously) or an isotype control monoclonal antibody. The animals then were challenged with 1 x 10(6) E. coli 018:K1 in the presence or absence of ceftazidime (50 mg/kg intravenously). There were four groups of six animals randomized to receive either anti-CD14 monoclonal antibody without ceftazidime, isotype control monoclonal antibody without ceftazidime, anti-CD14 monoclonal antibody with ceftazidime, or isotype control antibody with ceftazidime.


RESULTS
Serial measurement of quantitative bacteremia and endotoxemia was performed over 24 hrs after the administration of the bacterial challenge. Animals also underwent necropsy with quantitative bacterial cultures from multiple organ tissue samples. The anti-lapine CD14 monoclonal antibody significantly impaired the bloodstream clearance of E. coli (p <.01) and increased quantitative counts of E. coli in tissue culture samples when compared with isotype control antibody in the absence of simultaneous administration of ceftazidime. No differences in quantitative bacteremia, endotoxemia, or organ tissue counts were found after anti-CD14 antibody and control antibody-treated animals in the presence of ceftazidime treatment.


CONCLUSIONS
Anti-CD14 monoclonal antibody has the capacity to interfere with the innate immune response and systemic microbial clearance in experimental animals with E. coli bacteremia. The concomitant administration of effective antimicrobial therapy eliminated differences in the rate of microbial clearance between the control antibody and the CD14 monoclonal antibody. These results indicate that care should be taken in clinical trials with anti-CD14 monoclonal antibodies to ensure that adequate antimicrobial therapy is administered in the presence of systemic bacterial infection.
Opal
Steven M
SM
Brown University School of Medicine, Infectious Disease Division, Pawtucket, RI, USA. Steven_Opal@brown.edu
Palardy
John E
JE
Parejo
Nicolas
N
Jasman
Richard L
RL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D016470:Bacteremia / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D002442:Ceftazidime / Q000627:therapeutic use; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D004731:Endotoxins / Q000097:blood; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D005260:Female; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D011446:Prospective Studies; D011817:Rabbits; D011897:Random Allocation; D013154:Spleen / Q000382:microbiology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D018950:Lipopolysaccharide Receptors; D002442:Ceftazidime