Multicenter evaluation of a human monoclonal antibody to Enterobacteriaceae common antigen in patients with Gram-negative sepsis.
OBJECTIVE
To evaluate in Gram-negative sepsis patients the human monoclonal immunoglobulin M antibody (MAB-T88) directed at the enterobacterial common antigen which is a specific surface antigen closely linked to lipopolysaccharide and shared by all members of the Enterobacteriaceae family of Gram-negative bacteria.


METHODS
Prospective, randomized, double-blinded, placebo-controlled, multicenter trial.


METHODS
Thirty-three academic medical centers in the United States.


METHODS
Patients were entered with a clinical diagnosis of sepsis, the presence of either shock or multiple organ dysfunction, and presumptive evidence for Gram-negative infection.


METHODS
Patients received a single intravenous infusion, over 30 mins, of either 300 mg of MAB-T88 formulated in albumin, or placebo (albumin).


RESULTS
The primary analysis group was prospectively identified as those patients with documented evidence of an infection with bacteria of the family Enterobacteriaceae at any site. The primary end point was survival within the first 28 days. A total of 826 patients were enrolled with 55% (n = 455) in the primary analysis group. There were no significant differences between the intervention and control primary analysis group study groups for sites of infection, severity of illness, underlying medical conditions, adequacy of antibiotic or surgical treatment, or other baseline variables except for a higher frequency of chronic renal failure in the MAB-T88 group (4.4% vs. 1.3%, p=.051). The average Acute Physiology and Chronic Health Evaluation II scores were 26.8 +/- 8.6 (mean +/- sd) in the MAB-T88-treated group and 26.5 +/- 8.3 in the placebo-treated group (p =.72). There was no significant difference between MAB-T88- and placebo-treated groups during the first 28-day all-cause mortality in the primary analysis group (34.2% vs. 30.8%, p=.44) or in all 826 patients enrolled (37.0% vs. 34.0%, p=.36). On subset analysis, the use of MAB-T88 was not associated with significant mortality trends. More adverse events were seen with the use of MAB-T88 in the bacteremic enterobacterial common antigen group (p <.05).


CONCLUSIONS
Use of the human monoclonal antibody, MAB-T88, did not improve the mortality in patients with presumed Gram-negative sepsis or in those patients with proven enterobacterial common antigen infections. No subset trends were identified that would support further investigation of this agent in sepsis.
Albertson
Timothy E
TE
Department of Medicine, University of California, Davis, Sacramento, USA.
Panacek
Edward A
EA
MacArthur
Rodger D
RD
Johnson
Steven B
SB
Benjamin
Ernest
E
Matuschak
George M
GM
Zaloga
Gary
G
Maki
Dennis
D
Silverstein
Jeffrey
J
Tobias
Jeffrey K
JK
Haenftling
Kathy
K
Black
George
G
Cowens
J Wayne
JW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000276:immunology*; D004311:Double-Blind Method; D004755:Enterobacteriaceae / Q000276:immunology*; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial