Abstract

We described a comprehensive analysis of the molecular epidemiology of multidrug-resistant (MDR) P. aeruginosa. Molecular analysis included typing by Pulsed Field Gel Electrophoresis, identification of genes of interest through PCR-based assays and sequencing of target genes. Case-control study was conducted to better understand the prognostic of patients and the impact of inappropriate therapy in patients with bacteremia, as well as the risk factors of MDR infections. We observed a high rate of MDR isolates (40.7%), and 51.0% of them was independently associated with inappropriate antibiotic therapy. Bacteremia was detected in 66.9% of patients, and prolonged hospital stay was expressive in those resistant to fluoroquinolone. Plasmid-mediated quinolone resistance genes (PMQR), qnrS1 and aac(6’)Ib-cr, were detected in two different nosocomial isolates (5.3%), and the aac(6’)-Ib7 variant was detected at a high frequency (87.5%) in those negative to PMQR. The presence of mutations in gyrA and parC genes was observed in 100% and 85% of selected isolates, respectively. Isolates harboring PMQR genes or mutations in gyrA and parC were not closely related, except in those containing SPM (São Paulo metallo-β-lactamase) clone. In addition, there is no study published in Brazil to date reporting the presence of Pseudomonas aeruginosa isolates harboring both qnrS1 and aac(6’)Ib-cr genes, with alarming frequency of patients with inappropriate therapy.

Highlights

  • The increasing incidence of MDR P. aeruginosa is a global problem as a consequence of the ability of this microorganism to develop resistance to almost all antibioticsPLOS ONE | DOI:10.1371/journal.pone.0155914 May 24, 2016P. aeruginosa Carrying Plasmid-mediated quinolone resistance genes (PMQR) and blaSPM Genes that are available for treatment, either by mutations present in chromosomal gene, or by horizontal gene transfer [1,2]

  • Two case-control studies were conducted: (i) to determine the risk factors associated with MDR P. aeruginosa infections, and (ii) to determine the risk factors associated with antimicrobial resistance and treatment outcome in patients with P. aeruginosa bacteremia

  • From May 2009 to December 2012 and from April to October 2014, a total of 236 non-repetitive patients with P. aeruginosa infections at the University Hospital were included in the study

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Summary

Introduction

The increasing incidence of MDR P. aeruginosa is a global problem as a consequence of the ability of this microorganism to develop resistance to almost all antibioticsPLOS ONE | DOI:10.1371/journal.pone.0155914 May 24, 2016P. aeruginosa Carrying PMQR and blaSPM Genes that are available for treatment, either by mutations present in chromosomal gene, or by horizontal gene transfer [1,2]. The increasing incidence of MDR P. aeruginosa is a global problem as a consequence of the ability of this microorganism to develop resistance to almost all antibiotics. Its use has been threatened mainly by the increased incidence of isolates resistant to this class of antibiotics [7,8,9]. Among the carbapenem resistance mechanisms, there is the presence of carbapenemases, which are a heterogeneous group of β-lactamases comprising Classes A (penicillinases), B (metalloenzymes) and D (oxacillinases), with the ability to hydrolyze imipenem and meropenem in addition to other penicillins and cephalosporins [10]. The carbapenem resistance in P. aeruginosa infection occurs mainly by metallo-β-lactamase (MBL), in addition to the appearance of other β-lactamases with carbapenemase activity, including KPC (Klebsiella pneumoniae carbapenemase) and OXA-carbapenemase [7,9,13,14]

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