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 resistancedetermining regions (QRDRs), metallo-b-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 bla IMP , bla VIM , bla SIM , bla GIM and bla SPM 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 bla SPM genotype (66.6 %) and bla VIM 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.
INTRODUCTIONSevere infections such as bloodstream infection and ventilator-associated pneumonia (VAP) due to multidrugresistant (MDR) Pseudomonas aeruginosa result in greater morbidity and mortality, longer hospitalization and higher cost than infections caused by susceptible bacteria (Morales et al., 2012; Suárez et al., 2010;Voor In't Holt et al., 2014), and aspects related to epidemiology and the outcome of patients with these infections may change, resulting in high rates of resistance and as consequence difficulties in treatment (Kang et al., 2005; Lodise et al., 2007).Today, the emergence of MDR P. aeruginosa is a global problem (Sader et al., 2001; Van der Bij et al., 2011, resulting in the ability of this pathogen to develop resistance to almost all available antibiotics, either by selection of mutations in chromosomal genes or from horizontal gene transfer (Breidenstein et al., 2011). In Brazil this problem is hih5ghly significant and some studies show a very high density of antibiotic use, especially of carbapenems and fluoroquinolones (Moreira et al., 2013;Porto et al., 2013). The resistance of P. aeruginosa to carbapenems is higher than 60 % in some Brazilian hospitals ...