Monoclonal Anti-endotoxin Antibodies for the Treatment of Gram-negative Bacteremia and Septic Shock

Overview

Journal Eur J Clin Microbiol Infect Dis

Publisher Springer

Specialties Infectious Diseases
Microbiology

Date 1990 Oct 1

PMID 2261915

Citations 9

Authors

J D Baumgartner

Affiliations

Soon will be listed here.

Abstract

The role of anti-endotoxin antibodies in the management of gram-negative bacteremia and the experimental and clinical studies on the cross-protection afforded by core LPS antibodies are reviewed. These studies did not achieve clarification of the epitope(s) and effector mechanism(s) involved in protection. Recently, two anti-lipid A IgM monoclonal antibodies, designated E5 and HA-1A, have been investigated in patients with gram-negative bacterial infections and clinical manifestations of septicemia. E5 reduced the mortality of patients if they were not in shock, whether they were bacteremic or not. A confirmatory study has been initiated. In contrast to E5, HA-1A protected patients whether they were in shock or not, but only when they were bacteremic at randomization. Although these studies suggest beneficial effects, the type of patients who may benefit from this expensive therapy should be further defined. Further investigations are needed to clarify the mechanisms of protection of these antibodies.

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References

Miner K, Manyak C, Williams E, Jackson J, Jewell M, Gammon M . Characterization of murine monoclonal antibodies to Escherichia coli J5. Infect Immun. 1986; 52(1):56-62. PMC: 262197. DOI: 10.1128/iai.52.1.56-62.1986. View

Bryan C, Reynolds K, Brenner E . Analysis of 1,186 episodes of gram-negative bacteremia in non-university hospitals: the effects of antimicrobial therapy. Rev Infect Dis. 1983; 5(4):629-38. DOI: 10.1093/clinids/5.4.629. View

Young L, Gascon R, Alam S, Bermudez L . Monoclonal antibodies for treatment of gram-negative infections. Rev Infect Dis. 1989; 11 Suppl 7:S1564-71. DOI: 10.1093/clinids/11.supplement_7.s1564. View

McCabe W . Immunization with R mutants of S. Minnesota. I. Protection against challenge with heterologous gram-negative bacilli. J Immunol. 1972; 108(3):601-10. View

Calandra T, Glauser M, Schellekens J, Verhoef J . Treatment of gram-negative septic shock with human IgG antibody to Escherichia coli J5: a prospective, double-blind, randomized trial. J Infect Dis. 1988; 158(2):312-9. DOI: 10.1093/infdis/158.2.312. View

Hector R, Collins M, Pennington J . Treatment of experimental Pseudomonas aeruginosa pneumonia with a human IgM monoclonal antibody. J Infect Dis. 1989; 160(3):483-9. DOI: 10.1093/infdis/160.3.483. View

Pollack M, Raubitschek A, Larrick J . Human monoclonal antibodies that recognize conserved epitopes in the core-lipid A region of lipopolysaccharides. J Clin Invest. 1987; 79(5):1421-30. PMC: 424413. DOI: 10.1172/JCI112970. View

BRAUDE A, Douglas H . Passive immunization against the local Shwartzman reaction. J Immunol. 1972; 108(2):505-12. View

Pennington J . Impact of molecular biology on Pseudomonas aeruginosa immunization. J Hosp Infect. 1988; 11 Suppl A:96-102. DOI: 10.1016/0195-6701(88)90173-9. View

10.

Baumgartner J, Glauser M, McCutchan J, Ziegler E, van Melle G, Klauber M . Prevention of gram-negative shock and death in surgical patients by antibody to endotoxin core glycolipid. Lancet. 1985; 2(8446):59-63. DOI: 10.1016/s0140-6736(85)90176-x. View

11.

Bone R, Fisher Jr C, Clemmer T, Slotman G, Metz C, Balk R . A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med. 1987; 317(11):653-8. DOI: 10.1056/NEJM198709103171101. View

12.

Kreger B, Craven D, Carling P, McCabe W . Gram-negative bacteremia. III. Reassessment of etiology, epidemiology and ecology in 612 patients. Am J Med. 1980; 68(3):332-43. DOI: 10.1016/0002-9343(80)90101-1. View

13.

Teng N, Kaplan H, Hebert J, Moore C, Douglas H, Wunderlich A . Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies. Proc Natl Acad Sci U S A. 1985; 82(6):1790-4. PMC: 397358. DOI: 10.1073/pnas.82.6.1790. View

14.

. Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med. 1987; 317(11):659-65. DOI: 10.1056/NEJM198709103171102. View

15.

Pollack M, Chia J, Koles N, Miller M, Guelde G . Specificity and cross-reactivity of monoclonal antibodies reactive with the core and lipid A regions of bacterial lipopolysaccharide. J Infect Dis. 1989; 159(2):168-88. DOI: 10.1093/infdis/159.2.168. View

16.

Ziegler E, McCutchan J, Fierer J, Glauser M, Sadoff J, Douglas H . Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl J Med. 1982; 307(20):1225-30. DOI: 10.1056/NEJM198211113072001. View

17.

Jansson P, Lindberg A, Lindberg B, Wollin R . Structural studies on the hexose region of the core in lipopolysaccharides from Enterobacteriaceae. Eur J Biochem. 1981; 115(3):571-7. DOI: 10.1111/j.1432-1033.1981.tb06241.x. View

18.

DeMaria A, Carven D, Heffernan J, McIntosh T, Grindlinger G, McCabe W . Naloxone versus placebo in treatment of septic shock. Lancet. 1985; 1(8442):1363-5. DOI: 10.1016/s0140-6736(85)91787-8. View

19.

Westphal O, Jann K, Himmelspach K . Chemistry and immunochemistry of bacterial lipopolysaccharides as cell wall antigens and endotoxins. Prog Allergy. 1983; 33:9-39. View

20.

Kirkland T, Ziegler E . An immunoprotective monoclonal antibody to lipopolysaccharide. J Immunol. 1984; 132(5):2590-2. View