title: Observations using antiendotoxin antibody (E5) as adjuvant therapy in humans with suspected, serious, gram-negative sepsis.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of E5 (Xomen-E5), a murine monoclonal immunoglobulin M antibody, in reducing mortality in patients with serious Gram-negative infections. Phase II, single-site study.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled study.
  
  
  METHODS
  Surgical, neurosurgical and medical ICUs, comprising approximately 30 beds in a multidisciplinary university hospital.
  
  
  METHODS
  Patients with clinical evidence of serious infection admitted to the ICU for monitoring of vital signs and for intensive care nursing. Of the 39 patients enrolled in the study, 23 had documented Gram-negative infection.
  
  
  METHODS
  Patients suspected of having life-threatening Gram-negative infections received one of two doses of E5 or placebo. Safety and efficacy were assessed by survival on days 3, 7, and 21, appearance of adverse reactions, development of antimurine antibodies, and effects on BP, urine output, WBC count, and temperature.
  
  
  RESULTS
  Mortality rate from Gram-negative infection 3 days after the last drug (or placebo) infusion was two (22%) of nine deaths in the placebo group compared with 0 of nine for E5 2.5 mg/kg and 0 of five for E5 7.5 mg/kg. At 21 days after therapy, three patients treated with E5 had died. Only one of these three deaths resulted from infection. Eight of 15 E5 patients tested had immunoglobulin G antimurine antibodies by 3 wks after therapy began, but all were asymptomatic.
  
  
  CONCLUSIONS
  E5 was well tolerated and may have the potential to reduce early morbidity and the mortality rate in seriously ill patients with Gram-negative infections. Results from larger phase III studies are needed to confirm these findings.
authors.affiliation: Department of Medicine, St. Louis University, MO.
authors.forename: R N
authors.initials: RN
authors.lastname: Greenberg
authors.forename: K M
authors.initials: KM
authors.lastname: Wilson
authors.forename: A Y
authors.initials: AY
authors.lastname: Kunz
authors.forename: N I
authors.initials: NI
authors.lastname: Wedel
authors.forename: K J
authors.initials: KJ
authors.lastname: Gorelick
mesh_terms: D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003131:Combined Modality Therapy; D004306:Dose-Response Relationship, Immunologic; D004341:Drug Evaluation; D004731:Endotoxins / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D004731:Endotoxins; D007075:Immunoglobulin M