Review and Critique of the Use of Immunoglobulins in Prevention and Treatment of Infection in Critically Ill Patients

Abstract

of the use of immunoglobulins in prevention and treatment of infection in critically ill patients. Can J Infect Dis 1992;3(Suppl B):3B-10B. The study of standard intravenous immunoglobulin G (IVIG) preparations as adjunctive therapy in seriously ill patients is motivated by the possible need to: restore immunoglobulin G levels depleted after trauma or surgery; and/or to provide patients with specific antibodies directed against various microorganisms . Whereas no therapeutic efficacy h as been shown in clinical studies with standard IVIG , some data suggest a benefit in prophylactic use. Antisera or IVIG hyperimmune against the biologically active. highly conserved core portion of the endotoxin of Gram-negative bacteria have demonstrated variable degrees of protection in animal models and clinical trials. Two clinical trials using monoclonal antibodies against core lipopolysaccharide have been completed. Only subsets of patients with the Gram-negative sepsis syndrome were protected , but both studies gave discrepant results concerning the type of patients that were reported to benefit from administration of these antibodies. Further studies will be necessary to establish whether application of this therapy can be recommended. Key Words: Critically ill patients, Clinical trial, Immunoglobulin G Revue critique du recours aux immunoglobulines dans Ia prevention et le traitement de !'infection chez les patients gravement maladesLe besoin de restaurer les niveaux d'immunoglobulines G diminuees suite a un traumatisme ou une chirurgie et/ ou Ia necessite d'offrir aux patients des anticorps specifiques diriges contre des microorganismes varies justifient amplement !'etude des preparations d'immunoglobulines intraveineuses standard (IVIG) comme therapie adjuvante chez des patients tres malades. Alors qu'aucune investigation clinique n 'a demontre l'efficacite therapeutique des IVIG, quelques etudes semblent suggerer qu'elles puissent etre uilles comme agent prophylactique. Des antiserums ou des IVIG hyperimmunes diriges contre le "core" de l'endotoxine, Ia portion biologiquement active et Ia mieux conservee de l'endotoxime des bacteries a Gram-n egatif, ont demontre des degres variables de protection dans des modeles animaux et lors d'essais cliniques. Deux essais cliniques portant sur des anticorps monoclonaux diriges contre les "core" lipopolysaccharides ont ete effectues. Seuls des sous-groupes de patients porteurs de syndromes infectieux a Gram-negatif ont ete proteges, mais les deux etudes ont donne des resultats divergents relativement au type de patients qui auraient beneficie de !'administration de ces anticorps. D'autres etudes devront etre entrelprises pour etablir si !'application de ce traitement est recommandable. as a result of several immunological dysfunctions. Decreased levels of immunoglobulin G have been described, especially after trauma and surgery (1). Moreover. neutrophils undergo a decline with respect to chemotaxis, opsonic activity and ability to kill bacteria. In addition , such patients are ex...

Endotoxaemia, production of tumour necrosis factor ? and polymorphonuclear neutrophil activation following strenuous exercise in humans

“…Based on these studies, it would appear that administration of these molecules has a demonstrated therapeutic potential for these patients, especially when used prophylactically (Zanetti et al 1991). Although the mechanisms underlying the ecacy of anti-LPS antibodies remain unclear, immunization experiments performed by De and McCabe et al (1988) have indicated that the most protective elements are contained in the IgM class, IgG having no protective eect.…”

Non-antibiotic strategies for sepsis

“…The use of IVIG in sepsis also has a long history [24]. It was initially thought that it might be useful because it contained anti-endotoxin antibodies [25] but, despite several clinical trials, this idea never really gained currency, and IVIG has largely disappeared from routine clinical use for sepsis with the exception of patients with streptococcal toxic shock syndrome (STSS).…”

Influence of human anti-lipopolysaccharide immunoglobulins on tissue distribution and clearance of lipopolysaccharide in rats

“…This issue has assumed considerable importance, as evidenced by the controversy that has arisen concerning the results of clinical trials of anti-LPS antibodies for the treatment of sepsis [1,5,7,8,11,12,14,29,32,37,40]. In experimental animals, a single intravenous injection of Gram-negative bacterial LPS has been shown to produce hematological , hemodynamic and metabolic changes close to those observed in patients with sepsis [2,22].…”