RESUMO
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-ß-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 (53.3â%), and in blood we observed the blaSPM genotype (66.6â%) and blaVIM genotype (33.3â%). The exoS gene was found in all isolates, whilst the frequency was low for exoU (9.4â%). 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.
Assuntos
Antibacterianos/farmacologia , Bacteriemia/mortalidade , Sistemas de Secreção Bacterianos , Pneumonia Associada à Ventilação Mecânica/mortalidade , Infecções por Pseudomonas/mortalidade , Pseudomonas aeruginosa/isolamento & purificação , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Sistemas de Secreção Bacterianos/genética , Sistemas de Secreção Bacterianos/fisiologia , Brasil/epidemiologia , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Farmacorresistência Bacteriana Múltipla , Feminino , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Genótipo , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Estudos Retrospectivos , Fatores de Risco , Fatores de Virulência/genética , Adulto JovemRESUMO
The rates of multidrug-resistant, extensively drug-resistant and pandrug-resistant isolates amongst non-fermenting Gram-negative bacilli, particularly Pseudomonas aeruginosa, have risen worldwide. The clinical consequence of resistance and the impact of adverse treatment on the outcome of patients with P. aeruginosa bacteraemia remain unclear. To better understand the predictors of mortality, the clinical consequence of resistance and the impact of inappropriate therapy on patient outcomes, we analysed the first episode of P. aeruginosa bacteraemia in patients from a Brazilian tertiary-care hospital during the period from May 2009 to August 2011. Antimicrobial susceptibility testing was conducted; phenotypic detection of metallo-ß-lactamase (MBL) and PCR of MBL genes were performed on carbapenem-resistant strains. Amongst the 120 P. aeruginosa isolates, 45.8â% were resistant to carbapenem and 36 strains were tested for MBL detection. A total of 30â% were phenotypically positive and, of these, 77.8â% expressed an MBL gene, bla(SPM-1) (57â%) and bla(VIM-type) (43â%). The resistance rates to ceftazidime, cefepime, piperacillin/tazobactam, carbapenem, fluoroquinolone and aminoglycoside were 55, 42.5, 35, 45.8, 44 and 44â%, respectively. Previous antibiotic use, length of a hospital stay ≥30 days prior to P. aeruginosa, haemodialysis, tracheostomy, pulmonary source of bacteraemia and Intensive Care Unit admission were common independent risk factors for antimicrobial resistance. Cefepime resistance, multidrug resistance and extensive drug resistance were independently associated with inappropriate therapy, which was an important predictor of mortality, being synergistic with the severity of the underlying disease.