Shimizu Masaru, Katoh Hideya, Hamaoka Saeko, Kinoshita Mao, Akiyama Koichi, Naito Yoshifumi, Sawa Teiji
Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
J Infect Chemother. 2016 Apr;22(4):240-7. doi: 10.1016/j.jiac.2016.01.006. Epub 2016 Feb 8.
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.
多重耐药铜绿假单胞菌可导致与菌血症、脓毒症及死亡率密切相关的急性肺损伤，在免疫功能低下的情况下尤为如此。尽管免疫球蛋白溶液给药是免疫功能低下患者适用的免疫疗法，但免疫球蛋白给药对多重耐药铜绿假单胞菌肺炎的疗效尚未得到充分评估。在本研究中，我们在铜绿假单胞菌肺炎免疫功能低下小鼠模型中，研究了预防性给予免疫球蛋白溶液（静脉注射免疫球蛋白）与其他类型抗菌剂（如抗PcrV IgG、哌拉西林/他唑巴坦或黏菌素）相比的有效性。黏菌素是预防急性肺损伤、菌血症、细胞因子血症和脓毒症最有效的药物。在四种测试抗菌剂中，除黏菌素外，抗PcrV IgG和静脉注射免疫球蛋白在保护小鼠免于死亡方面最有效。哌拉西林/他唑巴坦不能预防急性肺损伤或菌血症；相反，它会使肺组织学恶化。数据表明，使用在体外药敏试验中获得阳性结果的药物并不总是能预防感染铜绿假单胞菌的白细胞减少宿主中的急性肺损伤。临床医生应考虑体外和体内试验结果存在差异的可能性，因为抗菌剂缺乏体外杀菌活性并不总是其在体内无法根除细菌的可靠预测指标，即使在免疫功能低下的宿主中也是如此。基于我们的研究结果，应重新评估静脉注射免疫球蛋白对铜绿假单胞菌诱导的急性肺损伤的潜在保护作用。
