Immunoprophylaxis against Klebsiella and Pseudomonas aeruginosa Infections

Abstract

To determine if passive immunization could decrease the incidence or severity of Klebsiella and Pseudomonas aeruginosa infections, patients admitted to intensive care units of 16 Department of Veterans Affairs and Department of Defense hospitals were randomized to receive either 100 mg/kg intravenous hyperimmune globulin (IVIG), derived from donors immunized with a 24-valent Klebsiella capsular polysaccharide plus an 8-valent P. aeruginosa O-polysaccharide-toxin A conjugate vaccine, or an albumin placebo. The overall incidence and severity of vaccine-specific Klebsiella plus Pseudomonas infections were not significantly different between the groups receiving albumin and IVIG. There was some evidence that IVIG may decrease the incidence (2.7% albumin vs. 1.2% IVIG) and severity (1.0% vs. 0.3%) of vaccine-specific Klebsiella infections, but these reductions were not statistically significant. The trial was stopped because it was statistically unlikely that IVIG would be protective against Pseudomonas infections at the dosage being used. Patients receiving IVIG had more adverse reactions (14.4% vs. 9.2%).

Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils

“…The anti-CPS vaccine approached worked well to protect rodents from death in experimental models of severe K. pneumoniae infection (39,40). The vaccine was evaluated for safety in humans (35), and the use of CPS-specific hyperimmune IVIG decreased the incidence and severity of Klebsiella infections in a human clinical trial (41). Previous work also demonstrated that vaccines (either monovalent or polyvalent) can protect against multiple (as many as 71) Klebsiella capsule types (35,42).…”

Human Monoclonal Antibodies toPseudomonas aeruginosaAlginate That Protect against Infection by Both Mucoid and Nonmucoid Strains

“…Efficacy against burn wound infection using immune globulin from patients immunized with a cellular extract of P. aeruginosa showed protective efficacy in the early 1980s (43,44) but this product was not further pursued. A hyperimmune IVIg product prepared from plasma donors immunized with an octavalent P. aeruginosa LPS O-side chain conjugate vaccine (45,46) showed no protective efficacy in patients in intensive care units (47). This may have been due to low Ab coverage for a sufficient diversity of serologically distinct O-Ags, or possibly to an overall low infection rate precluding an adequate sample size for documentation of the IVIg efficacy.…”

Intranasal immunization with heterologously expressed polysaccharide protects against multiple Pseudomonas aeruginosa infections

“…This same group is developing passive reagents (19); however, a clinical trial using i.v. hyperimmune globulin elicited with this same vaccine was stopped because of adverse effects and no evidence of efficacy (20). In mouse experiments, either intramuscular or IN administration of monovalent O antigen conjugates that were included in the octovalent vaccine was found to elicit an IgG response in the lung but only in the presence of adjuvant; only the IN immunization with adjuvant elicited an IgA response at that site.…”