OBJECTIVES We assessed the association between the lethality of Pseudomonas aeruginosa in a Caenorhabditis elegans model and outcomes of P. aeruginosa bloodstream infections. METHODS A total of 593 P. aeruginosa bloodstream isolates recovered from a prospective Spanish multicentre study were analysed. Clinical variables, susceptibility profiles and Type III Secretion System (TTSS) genotypes (exoU/exoS genes) were available from previous studies. A C. elegans virulence score (CEVS) was used, classifying the isolates into high (CEVS 4-5), intermediate (CEVS 3) and low (CEVS 1-2) virulence. The main outcome analysed was 30-day mortality. RESULTS Up to 75% (446/593) of the isolates showed a high-virulence phenotype, and 17% (101/593) a low-virulence one. No association between virulence phenotype and the main outcome variable (30-day mortality) was found (29/101 (28.7%) versus 127/446 (28.5%), p 1). However, an inverse association between C. elegans virulence and multidrug-resistant and extensively drug-resistant profiles was documented (OR 0.655 (95% CI 0.571-0.751) and OR 0.523 (95% CI 0.436-0.627), p <0.001, respectively), whereas the exoU genotype was significantly more frequent among isolates showing high virulence (10/101 (9.9%) versus 112/446 (25.1%), p <0.001). Moreover, although significance was not reached, strains showing a high-virulence phenotype tended to be associated with community-acquired infections (1/101 (1%) versus 25/446 (5.6%), p 0.065), whereas low-virulence phenotypes tended to be associated with a higher illness severity (such as higher median Pitt score: 2 (1-4) versus 1 (0-3), p 0.036, or initial multiorgan dysfunction: 17/101 (16.8%) versus 41/446 (9.2%), p 0.024), with some underlying conditions (such as chronic renal failure 24/101 (23.8%) versus 59/446 (13.2%), p 0.013), and with the respiratory source of infections (17/101 (16.8%) versus 45/446 (10.1%), p 0.058). CONCLUSIONS Our results indicate that the P. aeruginosa virulence phenotype in a C. elegans model correlates with virulence genotype (TTSS) and resistance profile, but it is a poor prognostic marker of mortality in bloodstream infections.

中文翻译：

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权衡毒力对铜绿假单胞菌血液感染结果的影响。

目的我们评估了秀丽隐杆线虫模型中的铜绿假单胞菌致死率与铜绿假单胞菌血液感染的预后之间的关系。方法对前瞻性西班牙多中心研究中回收的593株铜绿假单胞菌血流分离物进行了分析。临床变量，易感性和III型分泌系统（TTSS）基因型（exoU / exoS基因）可从以前的研究中获得。使用秀丽隐杆线虫（C. elegans）毒力评分（CEVS），将分离株分为高毒力（CEVS 4-5），中毒力（CEVS 3）和低毒力（CEVS 1-2）。分析的主要结果是30天死亡率。结果高达75％（446/593）的分离株表现出高毒力表型，而17％（101/593）则显示出低毒力表型。在毒力表型和主要结果变量（30天死亡率）之间未发现关联（29/101（28.7％）对127/446（28.5％），p 1）。然而，线虫毒力与多药耐药性和广泛耐药性之间存在负相关关系（OR 0.655（95％CI 0.571-0.751）和OR 0.523（95％CI 0.436-0.627），p <0.001 ），而在表现出高毒力的分离株中，exoU基因型的频率明显更高（10/101（9.9％）与112/446（25.1％），p <0.001）。此外，尽管没有达到显着性，但显示高毒力表型的菌株往往与社区获得性感染有关（1/101（1％）对25/446（5.6％），p = 0.065），而低毒力表型往往与疾病严重程度较高相关（例如，皮特中位数评分较高：2（1-4）对1（0-3），p 0.036或初始多器官功能障碍：17/101（16.8％）对41/446（9.2％），p 0.024），但有一些潜在疾病（例如慢性）肾功能衰竭为24/101（23.8％）对59/446（13.2％），P = 0.013），以及呼吸道感染源（17/101（16.8％）对45/446（10.1％），P 0.058）。结论我们的结果表明，秀丽隐杆线虫模型中的铜绿假单胞菌毒力表型与毒力基因型（TTSS）和抗药性相关，但它是血液感染死亡的不良预后指标。1％），P = 0.058）。结论我们的结果表明，秀丽隐杆线虫模型中的铜绿假单胞菌毒力表型与毒力基因型（TTSS）和耐药性相关，但它是血液感染死亡的不良预后指标。1％），P = 0.058）。结论我们的结果表明，秀丽隐杆线虫模型中的铜绿假单胞菌毒力表型与毒力基因型（TTSS）和抗药性相关，但它是血液感染死亡的不良预后指标。