June 13, 1994

Projected Impact of Monoclonal Anti-Endotoxin Antibody Therapy

Author Affiliations

From the Divisions of General Medicine (Drs Bates and Lee) and Clinical Epidemiology (Dr Lee), Department of Medicine, and the Clinical Initiatives Development Group (Drs Bates and Lee), Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.

Arch Intern Med. 1994;154(11):1241-1249. doi:10.1001/archinte.1994.00420110085010

Background:  The goals of this study were to evaluate the criteria for administration of HA-1A monoclonal antibody therapy from the HA-1A trial in patients with suspected gram-negative bacteremia and to evaluate the accuracy with which Bone's criteria for sepsis syndrome identify patients with gram-negative bacteremia.

Methods:  This prospective cohort study included 1509 episodes in which hospitalized patients had blood cultures performed in an urban tertiary-care hospital. The main outcome measures were gram-negative bacteremia and gram-negative sepsis.

Results:  Of 1509 episodes, 115 (8%) represented bacteremia and 40 (3%) included gram-negative rods. Of these 40 patients, nine died in the hospital, including five patients who had gram-negative sepsis; all five had another rapidly fatal disease. Using criteria for treatment and exclusions from the HA-1A trial, three of the patients with gram-negative bacteremia would have been treated, while at least 52 patients without gram-negative bacteremia might have received HA-1A therapy (positive predictive value of criteria, 5.5%). Of the 1509 episodes, sepsis syndrome as defined by Bone was present in 34 (2.3%). While 32 of the 34 patients had suspected gram-negative bacteremia, only five had blood cultures positive for gram-negative bacteria.

Conclusions:  In this population, current criteria for administration of monoclonal anti—endotoxin antibody therapy were not sensitive or specific for gram-negative bacteremia, and many patients with gram-negative sepsis were too ill from other conditions to benefit. Indiscriminate use of these therapies could thus be costly yet yield few benefits. To identify patients who should receive novel therapies, better risk-stratification methods and cost-effectiveness analysis are needed.(Arch Intern Med. 1994;154:1241-1249)