title: Molecular epidemiological survey of the quinolone- and carbapenem-resistant genotype and its association with the type III secretion system in Pseudomonas aeruginosa.
abstract: 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.
authors.affiliation: Laboratory of Microbiology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil.
authors.forename: Melina Lorraine
authors.initials: ML
authors.lastname: Ferreira
authors.affiliation: Laboratory of Microbiology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil.
authors.forename: Raquel Cavalcanti
authors.initials: RC
authors.lastname: Dantas
authors.affiliation: Laboratory of Microbiology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil.
authors.forename: Ana Luiza Souza
authors.initials: ALS
authors.lastname: Faria
authors.affiliation: Laboratory of Microbiology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil.
authors.forename: Iara Rossi
authors.initials: IR
authors.lastname: Gonçalves
authors.affiliation: Laboratory of Microbiology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Silveira de Brito
authors.affiliation: Laboratory of Microbiology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil.
authors.forename: Lícia Ludendorff
authors.initials: LL
authors.lastname: Queiroz
authors.affiliation: Laboratory of Microbiology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil.
authors.forename: Paulo P
authors.initials: PP
authors.lastname: Gontijo-Filho
authors.affiliation: Laboratory of Microbiology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil.
authors.forename: Rosineide Marques
authors.initials: RM
authors.lastname: Ribas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality*; D058947:Bacterial Secretion Systems / Q000235:genetics / Q000502:physiology; D001938:Brazil / Q000453:epidemiology; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality*; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D012189:Retrospective Studies; D012307:Risk Factors; D037521:Virulence Factors / Q000235:genetics; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D058947:Bacterial Secretion Systems; D015780:Carbapenems; D024841:Fluoroquinolones; D037521:Virulence Factors