Ferreira Melina Lorraine, Dantas Raquel Cavalcanti, Faria Ana Luiza Souza, Gonçalves Iara Rossi, Silveira de Brito Cristiane, Queiroz Lícia Ludendorff, Gontijo-Filho Paulo P, Ribas Rosineide Marques
Laboratory of Microbiology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil.
J Med Microbiol. 2015 Mar;64(Pt 3):262-271. doi: 10.1099/jmm.0.000023. Epub 2015 Jan 16.
This study evaluated the predictors of mortality and the impact of inappropriate therapy on the outcomes of patients with bacteraemia and ventilator-associated pneumonia (VAP). Additionally, we evaluated the correlation of the type III secretion system (TTSS) effector genotype with resistance to carbapenems and fluoroquinolones, mutations in the quinolone resistance-determining regions (QRDRs), metallo-β-lactamase and virulence factors. A retrospective cohort was conducted at a tertiary hospital in patients with multidrug-resistant (MDR) P. aeruginosa bacteraemia (157 patients) and VAP (60 patients). The genes for blaIMP, blaVIM, blaSIM, blaGIM and blaSPM and virulence genes (exoT, exoS, exoY, exoU, lasB, algD and toxA) were detected; sequencing was conducted for QRDR genes on fluoroquinolone-resistant strains. The multivariate analyses showed that the predictors independently associated with death in patients with bacteraemia were cancer and inappropriate therapy. Carbapenem resistance was more frequent among strains causing VAP (53.3 %), and in blood we observed the blaSPM genotype (66.6 %) and blaVIM genotype (33.3 %). The exoS gene was found in all isolates, whilst the frequency was low for exoU (9.4 %). Substitution of threonine to isoleucine at position 83 in gyrA was the most frequent mutation among fluoroquinolone-resistant strains. Our study showed a mutation at position 91 in the parC gene (Glu91Lys) associated with a mutation in gyrA (Thre83Ile) in a strain of extensively drug-resistant P. aeruginosa, with the exoT(+)exoS(+)exoU(+) genotype, that has not yet been described in Brazil to the best of our knowledge. This comprehensive analysis of resistance mechanisms to carbapenem and fluoroquinolones and their association with TTSS virulence genes, covering MDR P. aeruginosa in Brazil, is the largest reported to date.
本研究评估了菌血症和呼吸机相关性肺炎（VAP）患者的死亡预测因素以及不恰当治疗对其结局的影响。此外，我们还评估了III型分泌系统（TTSS）效应子基因型与对碳青霉烯类和氟喹诺酮类药物耐药性、喹诺酮耐药决定区（QRDRs）突变、金属β-内酰胺酶及毒力因子之间的相关性。在一家三级医院对多重耐药（MDR）铜绿假单胞菌菌血症患者（157例）和VAP患者（60例）进行了一项回顾性队列研究。检测了blaIMP、blaVIM、blaSIM、blaGIM和blaSPM基因及毒力基因（exoT、exoS、exoY、exoU、lasB、algD和toxA）；对耐氟喹诺酮菌株的QRDR基因进行了测序。多因素分析显示，菌血症患者中与死亡独立相关的预测因素是癌症和不恰当治疗。引起VAP的菌株中碳青霉烯类耐药更为常见（53.3%），在血液中我们观察到blaSPM基因型（66.6%）和blaVIM基因型（33.3%）。在所有分离株中均发现了exoS基因，而exoU基因的频率较低（9.4%）。gyrA基因第83位苏氨酸替换为异亮氨酸是耐氟喹诺酮菌株中最常见的突变。我们的研究显示，一株广泛耐药铜绿假单胞菌的parC基因第91位（Glu91Lys）发生突变，与gyrA基因（Thre83Ile）突变相关，具有exoT(+)exoS(+)exoU(+)基因型，据我们所知，在巴西尚未有过此类报道。这项针对巴西MDR铜绿假单胞菌对碳青霉烯类和氟喹诺酮类药物的耐药机制及其与TTSS毒力基因关联的综合分析是迄今为止报道的规模最大的研究。
