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      Drivers of Irrational Use of Antibiotics in Europe

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          Abstract

          The unnecessary use of antibiotics and concomitant rapid growth of antibiotic resistance (ABR) is a widely acknowledged threat to global health, development, and sustainability. While the underlying cause of ABR is undoubtedly the overall volume of antibiotic use in general, irrational antibiotic use, which is influenced by several interrelated factors, is a major contributory factor. Here, we aimed to present and describe selected main drivers of irrational use of antibiotics in Europe. We performed a broad search of the current literature in databases such as PubMed, Google Scholar, Cochrane, as well as various institutional websites (World Health Organization, European Observatory, European Commission) to provide a new perspective on selected drivers of irrational antibiotic use in Europe. We also searched for relevant literature using snowballing, i.e., using reference lists of papers to identify additional papers. In this narrative review, we present that major factors among the general public driving antibiotic resistance are lack of public knowledge and awareness, access to antibiotics without prescription and leftover antibiotics, and knowledge attitude and perception of prescribers and dispensers, inadequate medical training, pharmaceutical promotion, lack of rapid and sufficient diagnostic tests, and patient–doctor interaction as major factors among healthcare providers. We further discuss initiatives that, if taken and implemented, can have an impact on and improve the current situation in Europe.

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          Most cited references45

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          Mechanisms of antimicrobial resistance in bacteria.

          The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g., beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop.
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            Randomized Trial of Rapid Multiplex Polymerase Chain Reaction-Based Blood Culture Identification and Susceptibility Testing.

            The value of rapid, panel-based molecular diagnostics for positive blood culture bottles (BCBs) has not been rigorously assessed. We performed a prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly from positive BCBs.
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              Impact of rapid organism identification via matrix-assisted laser desorption/ionization time-of-flight combined with antimicrobial stewardship team intervention in adult patients with bacteremia and candidemia.

              Integration of rapid diagnostic testing via matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) with antimicrobial stewardship team (AST) intervention has the potential for early organism identification, customization of antibiotic therapy, and improvement in patient outcomes. The objective of this study was to assess the impact of this combined approach on clinical and antimicrobial therapy-related outcomes in patients with bloodstream infections. A pre-post quasi-experimental study was conducted to analyze the impact of MALDI-TOF with AST intervention in patients with bloodstream infections. The AST provided evidence-based antibiotic recommendations after receiving real-time notification following blood culture Gram stain, organism identification, and antimicrobial susceptibilities. Outcomes were compared to a historic control group. A total of 501 patients with bacteremia or candidemia were included in the final analysis: 245 patients in the intervention group and 256 patients in the preintervention group. MALDI-TOF with AST intervention decreased time to organism identification (84.0 vs 55.9 hours, P < .001), and improved time to effective antibiotic therapy (30.1 vs 20.4 hours, P = .021) and optimal antibiotic therapy (90.3 vs 47.3 hours, P < .001). Mortality (20.3% vs 14.5%), length of intensive care unit stay (14.9 vs 8.3 days) and recurrent bacteremia (5.9% vs 2.0%) were lower in the intervention group on univariate analysis, and acceptance of an AST intervention was associated with a trend toward reduced mortality on multivariable analysis (odds ratio, 0.55, P = .075). MALDI-TOF with AST intervention decreased time to organism identification and time to effective and optimal antibiotic therapy.
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                Author and article information

                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                23 December 2018
                January 2019
                : 16
                : 1
                : 27
                Affiliations
                Global Health-Health Systems and Policy: Medicines, Focusing Antibiotics, Department of Public Health Sciences, Karolinska Institutet, 171 77 Stockholm, Sweden; Cecilia.Stalsby.Lundborg@ 123456ki.se
                Author notes
                [* ]Correspondence: anna.machowska@ 123456ki.se ; Tel.: +46-(0)-8-524-833-84
                Author information
                https://orcid.org/0000-0001-6525-1861
                Article
                ijerph-16-00027
                10.3390/ijerph16010027
                6338985
                30583571
                a575ddc2-0651-41a6-ba2b-55e57f25cdad
                © 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
                : 12 October 2018
                : 19 December 2018
                Categories
                Review

                Public health
                antibiotics,antibiotic resistance,irrational use,unnecessary antibiotic use,europe
                Public health
                antibiotics, antibiotic resistance, irrational use, unnecessary antibiotic use, europe

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