• Hideya Katoh, Hiroaki Yasumoto, Masaru Shimizu, Saeko Hamaoka, Mao Kinoshita, Koichi Akiyama, and Teiji Sawa.
• All authors: Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
• Crit. Care Med. 2016 Jan 1; 44 (1): e12-24.

ObjectivesVirulent and multidrug-resistant Pseudomonas aeruginosa causes a lethal pneumonia, especially in patients who are artificially ventilated. It has been reported that the virulence mechanism used by P. aeruginosa, which is linked to acute lung injury, is strongly associated with the type III secretion system, and specific antibodies targeting this system have shown a protective effect in both experimental and clinical settings. We investigated the effect of administering IV immunoglobulins on P. aeruginosa pneumonia, including its associated bacteremia and mortality, although focusing especially on type III secretion system-associated P. aeruginosa virulence.DesignProspective randomized and controlled animal study.SettingUniversity laboratory.SubjectsMale ICR mice.InterventionsMice were infected intratracheally with a lethal dose of the virulent P. aeruginosa PA103 strain. IV immunoglobulin administration was examined in three different settings: 1) premixed; 2) pre-IV, prophylactic administration before bacterial infection; and 3) post-IV, therapeutic administration after bacterial infection. The effect of specific antigen titer depletion of IV immunoglobulins was also examined.Measurements And Main ResultsSurvival and body temperature were monitored for 24 hours. Bacteremia, cytokine concentration, myeloperoxidase activity, WBC counts in the blood, and lung bacterial load were evaluated. Survival improved significantly in mice that received IV immunoglobulins (p < 0.05). Lung edema, lung bacteriologic load, and bacteremia decreased significantly in the IV immunoglobulin-treated mice (p < 0.05). The mechanism of protection was associated with the presence of antibodies against both PcrV and some bacterial surface antigens in the IV immunoglobulins.ConclusionsIV immunoglobulin administration had a significantly protective effect against lethal infection from virulent P. aeruginosa. Prophylactic IV immunoglobulin administration at the highest dose was comparable with that achieved by administrating a specific anti-PcrV polyclonal IgG into the mice. The mechanism of protection is likely to involve the synergic action of anti-PcrV titers and antibodies against some surface antigen(s) that block the type III secretion system-associated virulence of P. aeruginosa.

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