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      Clinical and Molecular Epidemiology of Multidrug-Resistant P. aeruginosa Carrying aac(6')-Ib-cr, qnrS1 and bla SPM Genes in Brazil

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          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), qnrS 1 and aac(6’)Ib-cr, were detected in two different nosocomial isolates (5.3%), and the aac(6’)-Ib 7 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 qnrS 1 and aac(6’)Ib-cr genes, with alarming frequency of patients with inappropriate therapy.

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          Most cited references41

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          Carbapenemases: the versatile beta-lactamases.

          Carbapenemases are beta-lactamases with versatile hydrolytic capacities. They have the ability to hydrolyze penicillins, cephalosporins, monobactams, and carbapenems. Bacteria producing these beta-lactamases may cause serious infections in which the carbapenemase activity renders many beta-lactams ineffective. Carbapenemases are members of the molecular class A, B, and D beta-lactamases. Class A and D enzymes have a serine-based hydrolytic mechanism, while class B enzymes are metallo-beta-lactamases that contain zinc in the active site. The class A carbapenemase group includes members of the SME, IMI, NMC, GES, and KPC families. Of these, the KPC carbapenemases are the most prevalent, found mostly on plasmids in Klebsiella pneumoniae. The class D carbapenemases consist of OXA-type beta-lactamases frequently detected in Acinetobacter baumannii. The metallo-beta-lactamases belong to the IMP, VIM, SPM, GIM, and SIM families and have been detected primarily in Pseudomonas aeruginosa; however, there are increasing numbers of reports worldwide of this group of beta-lactamases in the Enterobacteriaceae. This review updates the characteristics, epidemiology, and detection of the carbapenemases found in pathogenic bacteria.
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            Multidrug-resistant Pseudomonas aeruginosa: risk factors and clinical impact.

            Pseudomonas aeruginosa, a leading nosocomial pathogen, may become multidrug resistant (MDR). Its rate of occurrence, the individual risk factors among affected patients, and the clinical impact of infection are undetermined. We conducted an epidemiologic evaluation and molecular typing using pulsed-field gel electrophoresis (PFGE) of 36 isolates for 82 patients with MDR P. aeruginosa and 82 controls matched by ward, length of hospital stay, and calendar time. A matched case-control study identified individual risk factors for having MDR P. aeruginosa, and a retrospective matched-cohort study examined clinical outcomes of such infections. The 36 isolates belonged to 12 PFGE clones. Two clones dominated, with one originating in an intensive care unit (ICU). Cases and controls had similar demographic characteristics and numbers of comorbid conditions. A multivariate model identified ICU stay, being bedridden, having high invasive devices scores, and being treated with broad-spectrum cephalosporins and with aminoglycosides as significant risk factors for isolating MDR P. aeruginosa. Having a malignant disease was a protective factor (odds ratio [OR] = 0.2; P = 0.03). MDR P. aeruginosa was associated with severe outcomes compared to controls, including increased mortality (OR = 4.4; P = 0.04), hospital stay (hazard ratio, 2; P = 0.001), and requirement for procedures (OR = 5.4; P = 0.001). The survivors functioned more poorly at discharge than the controls, and more of the survivors were discharged to rehabilitation centers or chronic care facilities. The epidemiology of MDR P. aeruginosa is complex. Critically ill patients that require intensive care and are treated with multiple antibiotic agents are at high risk. MDR P. aeruginosa infections are associated with severe adverse clinical outcomes.
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              Impact of multidrug-resistant Pseudomonas aeruginosa infection on patient outcomes.

              Rates of antibiotic resistance in Pseudomonas aeruginosa are increasing worldwide. The multidrug-resistant (MDR) phenotype in P. aeruginosa could be mediated by several mechanisms including multidrug efflux systems, enzyme production, outer membrane protein (porin) loss and target mutations. Currently, no international consensus on the definition of multidrug resistance exists, making direct comparison of the literature difficult. Inappropriate empirical therapy has been associated with increased mortality in P. aeruginosa infections; delays in starting appropriate therapy may contribute to increased length of hospital stay and persistence of infection. In addition, worse clinical outcomes may be associated with MDR infections owing to limited effective antimicrobial options. This article aims to summarize the contemporary literature on patient outcomes following infections caused by drug-resistant P. aeruginosa. The impact of antimicrobial therapy on patient outcomes, mortality and morbidity; and the economic impact of MDR P. aeruginosa infections will be examined.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                24 May 2016
                2016
                : 11
                : 5
                : e0155914
                Affiliations
                [1 ]Instituto de Ciências Biomédicas (ICBIM), Laboratory of Molecular Microbiology, Universidade Federal de Uberlandia (UFU), Uberlandia, Minas Gerais, Brazil
                [2 ]Instituto de Ciências Biomédicas (ICBIM), Laboratory of Virology, Universidade Federal de Uberlandia (UFU), Uberlandia, Minas Gerais, Brazil
                University of North Dakota, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: BFA PPGF RMR. Performed the experiments: BFA MLF PADC SR RCCD IRG ALSF CSDB DWDFB RMR PPGF JY. Analyzed the data: BFA MLF PADC SR RCCD IRG ALSF CSDB DWDFB RMR PPGF JY. Contributed reagents/materials/analysis tools: RMR PPGF JY. Wrote the paper: BFA RMR PPGF JY.

                Article
                PONE-D-16-06399
                10.1371/journal.pone.0155914
                4878783
                27219003
                72142eb1-831d-4a00-acc7-ac696d47fc18
                © 2016 Araujo et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 February 2016
                : 8 May 2016
                Page count
                Figures: 2, Tables: 4, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004901, Fundação de Amparo à Pesquisa do Estado de Minas Gerais;
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                FAPEMIG (Fundação de Amparo à Pesquisa de Minas Gerais) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) provided financial support and scholarships.
                Categories
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                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Bacterial Pathogens
                Pseudomonas Aeruginosa
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Bacterial Pathogens
                Pseudomonas Aeruginosa
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                Pseudomonas
                Pseudomonas Aeruginosa
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                Antimicrobial Resistance
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                Nosocomial Infections
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