Thaden Joshua T, Keller Ashley E, Shire Norah J, Camara M Margarita, Otterson Linda, Huband Mike, Guenther Caitlin M, Zhao Wei, Warrener Paul, Stover C Kendall, Fowler Vance G, DiGiandomenico Antonio
Division of Infectious Diseases, Duke University, Durham, North Carolina.
MedImmune, LLC, Gaithersburg, Maryland.
J Infect Dis. 2016 Feb 15;213(4):640-8. doi: 10.1093/infdis/jiv436. Epub 2015 Sep 2.
The type 3 secretion protein PcrV and Psl exopolysaccharide are promising therapeutic antibody targets against Pseudomonas aeruginosa. We examined P. aeruginosa bloodstream infection (BSI) isolates for the ability to express PcrV and Psl and evaluated corresponding patient serum for active titers to these targets.
We identified 114 patients with acute P. aeruginosa BSI; 56 cases were accompanied by acute sera. Serum was evaluated for PcrV- and Psl-specific immunoglobulin G (IgG) and for cytotoxicity and opsonophagocytosis. Isolates were evaluated for susceptibility to antibiotics, expression of PcrV and Psl, and susceptibility to the anti-PcrV/Psl bispecific antibody and clinical candidate MEDI3902.
In-hospital mortality for patients with P. aeruginosa BSI was 39%. A total of 26% of isolates were resistant to ≥3 antibiotic classes. Although PcrV and/or Psl were detected in 99% of isolates, a majority of patients lacked active titers to PcrV (100%) and Psl (98%). In addition, MEDI3902 was active against all tested isolates.
A vast majority of P. aeruginosa BSI isolates express PcrV and Psl; however, patient sera most often lacked IgG and functionally active responses to these targets. These results suggest that therapies directed at PcrV and Psl could be a promising approach for combating P. aeruginosa bloodstream infections.
3型分泌蛋白PcrV和Psl胞外多糖是抗铜绿假单胞菌的有前景的治疗性抗体靶点。我们检测了铜绿假单胞菌血流感染（BSI）分离株表达PcrV和Psl的能力，并评估了相应患者血清中针对这些靶点的活性滴度。
我们确定了114例急性铜绿假单胞菌BSI患者；56例伴有急性期血清。评估血清中PcrV和Psl特异性免疫球蛋白G（IgG）以及细胞毒性和调理吞噬作用。评估分离株对抗生素的敏感性、PcrV和Psl的表达以及对抗PcrV/Psl双特异性抗体和临床候选药物MEDI3902的敏感性。
铜绿假单胞菌BSI患者的院内死亡率为39%。共有26%的分离株对≥3类抗生素耐药。尽管在99%的分离株中检测到了PcrV和/或Psl，但大多数患者缺乏针对PcrV（100%）和Psl（98%）的活性滴度。此外，MEDI3902对所有测试分离株均有活性。
绝大多数铜绿假单胞菌BSI分离株表达PcrV和Psl；然而，患者血清通常缺乏针对这些靶点的IgG和功能性活性反应。这些结果表明，针对PcrV和Psl的治疗可能是对抗铜绿假单胞菌血流感染的一种有前景的方法。
