title: Protective effects of intravenous immunoglobulin and antimicrobial agents on acute pneumonia in leukopenic mice.
abstract: Multi-drug resistant Pseudomonas aeruginosa causes the type of acute lung injury that is strongly associated with bacteremia, sepsis, and mortality, especially under immunocompromised conditions. Although administration of immunoglobulin solution is an applicable immunotherapy in immunocompromised patients, efficacy of immunoglobulin administration against multi-drug resistant P. aeruginosa pneumonia has not been well evaluated. In this study, we investigated the effectiveness of prophylactic administration of immunoglobulin solution (IVIG) in comparison with that of other types of antimicrobial agents, such as anti-PcrV IgG, piperacillin/tazobactam, or colistin in an immunocompromised mouse model of P. aeruginosa pneumonia. Colistin was the most effective agent for preventing acute lung injury, bacteremia, cytokinemia, and sepsis. Among the four tested antimicrobial agents, after colistin, anti-PcrV IgG and IVIG were the most effective at protecting mice from mortality. Piperacillin/tazobactam did not prevent acute lung injury or bacteremia; rather, it worsened lung histology. The data suggest that using an agent for which a positive result in an in vitro susceptibility test has been obtained may not always prevent acute lung injury in a leukopenic host infected with P. aeruginosa. Clinicians should consider the possibility of discrepancies between in vitro and in vivo tests because the absence of in vitro bactericidal activity in an antimicrobial agent is not always a reliable predictor of its lack of ability to eradicate bacteria in vivo, even in immunocompromised hosts. Based on our findings, the potential protective effects of IVIG against the acute lung injury induced by P. aeruginosa should be reevaluated.
authors: Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Masaru
authors: M
authors: Shimizu
authors: Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Hideya
authors: H
authors: Katoh
authors: Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Saeko
authors: S
authors: Hamaoka
authors: Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Mao
authors: M
authors: Kinoshita
authors: Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Koichi
authors: K
authors: Akiyama
authors: Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Yoshifumi
authors: Y
authors: Naito
authors: Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: anesth@koto.kpu-m.ac.jp.
authors: Teiji
authors: T
authors: Sawa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001831:Body Temperature; D003091:Colistin / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004487:Edema; D007074:Immunoglobulin G / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007970:Leukopenia / Q000150:complications / Q000188:drug therapy*; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D010878:Piperacillin / Q000627:therapeutic use; D018410:Pneumonia, Bacterial / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D065129:Pre-Exposure Prophylaxis; D020011:Protective Agents / Q000627:therapeutic use*; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D011550:Pseudomonas aeruginosa; D000078142:Tazobactam
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D020011:Protective Agents; D010397:Penicillanic Acid; D009195:Peroxidase; D000078142:Tazobactam; D010878:Piperacillin; D003091:Colistin
keywords: Antimicrobial agent; Immunocompromised host; Intravenous immunoglobulin; PcrV; Pneumonia; Pseudomonas aeruginosa