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      Multidrug-Resistant Gram-Negative Bacilli: A Retrospective Study of Trends in a Tertiary Healthcare Unit

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          Abstract

          Background and objective: Bacterial multidrug resistance is particularly common in Gram-negative bacilli (GNB), with important clinical consequences regarding their spread and treatment options. The aim of this study was to investigate the trend of multidrug-resistant GNB (MDR-GNB) in high-risk hospital departments, between 2000–2015, in intervals of five years, with the intention of improving antibiotic therapy policies and optimising preventive and control practices. Materials and methods: This is an observational, retrospective study performed in three departments of the most important tertiary healthcare unit in the southwestern part of Romania: the Intensive Care Unit (ICU), the General Surgery Department (GSD), and the Nutrition and Metabolic Diseases Department (NMDD). MDR was defined as acquired resistance to at least one agent in three or more antimicrobial categories. Trends over time were determined by the Cochran–Armitage trend test and linear regression. Results: During the study period, a total of 2531 strains of MDR-GNB were isolated in 1999 patients: 9.20% in 2000, 18.61% in 2005, 37.02% in 2010, and 35.17% in 2015. The most significant increasing trend was recorded in the ICU (gradient = 7.63, R² = 0.842, p < 0.001). The most common MDR-GNB in the ICU was isolated from bronchoalveolar aspiration samples. Concerning the proportion of different species, most of the changes were recorded in the ICU, where a statistically significant increasing trend was observed for Proteus mirabilis (gradient = 2.62, R 2 = 0.558, p < 0.001) and Acinetobacter baumannii (gradient = 2.25, R 2 = 0.491, p < 0.001). Analysis of the incidence of the main resistance phenotypes proportion identified a statistically significant increase in carbapenem resistance in the ICU (Gradient = 8.27, R² = 0.866, p < 0.001), and an increased proportion of aminoglycoside-resistant strains in all three departments, but more importantly in the ICU and GSD. Conclusion: A statistically significant increasing trend was observed in all three departments; the most significant one was recorded in the ICU, where after 2010, carbapenem-resistant strains were isolated.

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          Combating antimicrobial resistance: policy recommendations to save lives.

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            Mechanisms of antimicrobial resistance in Gram-negative bacilli

            The burden of multidrug resistance in Gram-negative bacilli (GNB) now represents a daily issue for the management of antimicrobial therapy in intensive care unit (ICU) patients. In Enterobacteriaceae, the dramatic increase in the rates of resistance to third-generation cephalosporins mainly results from the spread of plasmid-borne extended-spectrum beta-lactamase (ESBL), especially those belonging to the CTX-M family. The efficacy of beta-lactam/beta-lactamase inhibitor associations for severe infections due to ESBL-producing Enterobacteriaceae has not been adequately evaluated in critically ill patients, and carbapenems still stands as the first-line choice in this situation. However, carbapenemase-producing strains have emerged worldwide over the past decade. VIM- and NDM-type metallo-beta-lactamases, OXA-48 and KPC appear as the most successful enzymes and may threaten the efficacy of carbapenems in the near future. ESBL- and carbapenemase-encoding plasmids frequently bear resistance determinants for other antimicrobial classes, including aminoglycosides (aminoglycoside-modifying enzymes or 16S rRNA methylases) and fluoroquinolones (Qnr, AAC(6′)-Ib-cr or efflux pumps), a key feature that fosters the spread of multidrug resistance in Enterobacteriaceae. In non-fermenting GNB such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia, multidrug resistance may emerge following the sole occurrence of sequential chromosomal mutations, which may lead to the overproduction of intrinsic beta-lactamases, hyper-expression of efflux pumps, target modifications and permeability alterations. P. aeruginosa and A. baumannii also have the ability to acquire mobile genetic elements encoding resistance determinants, including carbapenemases. Available options for the treatment of ICU-acquired infections due to carbapenem-resistant GNB are currently scarce, and recent reports emphasizing the spread of colistin resistance in environments with high volume of polymyxins use elicit major concern. Electronic supplementary material The online version of this article (doi:10.1186/s13613-015-0061-0) contains supplementary material, which is available to authorized users.
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              Risk factors for the isolation of multi-drug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa: a systematic review of the literature.

              An understanding of the epidemiology of multi-drug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa infections is necessary in order to develop strategies to curtail their spread. For this purpose, the evidence linking the isolation of MDR A. baumannii and P. aeruginosa with specific risk factors was evaluated. PubMed was searched for the 20-year period from September 1985 to September 2005, and eligible studies were considered to be those that: (1) linked the isolation of A. baumannii and P. aeruginosa with specific risk factors; (2) described the characteristics of the affected patients in detail; and (3) provided data on the antibiotic resistance profile of the isolated micro-organisms. Fifty-five studies were found referring to A. baumannii (28 with case-control methodology and 27 outbreak investigations without case-control methodology), and 42 studies were found referring to P. aeruginosa (25 with case-control methodology and 17 outbreak investigations without case-control methodology). Although heterogeneous study designs and investigated risk factors limited this analysis, it was concluded that acquisition and spread of these micro-organisms appear to be related to a large number of variables. Among the most important were deficiencies in the implementation of infection control guidelines and the use of broad-spectrum antibiotics. Use of carbapenems and third-generation cephalosporins appear to be related to the development of an MDR phenotype by A. baumannii, while carbapenems and fluoroquinolones are implicated in MDR P. aeruginosa. The diversity of risk factors associated with the development of MDR A. baumannii and P. aeruginosa suggests that a separate outbreak investigation should be performed in each hospital setting. The development of innovative control strategies is needed in order to limit the spread of these pathogens.
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                Author and article information

                Journal
                Medicina (Kaunas)
                medicina
                Medicina
                MDPI
                1010-660X
                1648-9144
                26 November 2018
                December 2018
                : 54
                : 6
                : 92
                Affiliations
                [1 ]“Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Street, No. 2, 300041 Timișoara, Romania; deliacristimuntean@ 123456yahoo.com (D.M.); lumiere1tm@ 123456yahoo.com (L.B.); vicdumi@ 123456yahoo.com (V.D.); bagiuiulia@ 123456yahoo.com (I.-C.B.); deliahorhat@ 123456yahoo.com (D.-I.H.); dan_andrei.radu@ 123456yahoo.com (D.A.C.); dugador06@ 123456yahoo.com (D.D.); lickermonica@ 123456yahoo.com (M.L.)
                [2 ]“Pius Brînzeu” Emergency Clinical County Hospital, Liviu Rebreanu Street, No. 156, 300723 Timișoara, Romania; anca.krasta@ 123456yahoo.com
                [3 ]Children Emergency “Louis Turcanu” Timisoara, Iosif Nemoianu Street, No. 2, 300011 Timișoara, Romania
                Author notes
                [* ]Correspondence: horhat.florin@ 123456umft.ro ; Tel.: +40-722-369-675
                Author information
                https://orcid.org/0000-0001-6133-0204
                https://orcid.org/0000-0002-9245-5883
                Article
                medicina-54-00092
                10.3390/medicina54060092
                6307078
                30486311
                f9bf48c3-ce1d-4282-a531-1ef7287ad40b
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 05 October 2018
                : 20 November 2018
                Categories
                Article

                multidrug-resistant,gram-negative bacilli,tertiary hospital

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