Treatment of experimental Pseudomonas aeruginosa pneumonia with a human IgM monoclonal antibody

Abstract

A human IgM monoclonal antibody (MA-1C1) to Fisher immunotype 3 Pseudomonas aeruginosa lipopolysaccharide antigen was evaluated for in vivo activity in a guinea pig model of experimental pneumonia. Pharmacokinetics of MA-1C1 were compared in infected and noninfected animals. Intravenous bolus infusion of MA-1C1, 1 mg/kg, resulted in peak serum antibody concentrations of 3.8 +/- 0.08 and 3.7 +/- 0.05 micrograms/ml in infected and noninfected animals, respectively. Serum half-lives were 25 and 22 h in infected and noninfected groups. Treatment with a single intravenous infusion of MA-1C1 improved survival from pneumonia and was effective over a broad dose range (0.1-2.5 mg/kg). Cumulative survivals were 18 of 47 in the MA-1C1 group and 0 of 31 in controls (P less than .001). Treatment with MA-1C1 also resulted in fewer positive blood cultures 12 h after infection (P = .04). Although MA-1C1 penetrated into inflamed bronchial fluids, local concentrations were only 5% of the concentrations achieved in serum. Thus, MA-1C1 seems to provide significant therapeutic activity against experimental P. aeruginosa pneumonia by preventing dissemination of infection from the lung.