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      A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance

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          Abstract

          Background

          Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substantially less than from hospitalized patients on whom guidelines are often based. We therefore chose to assess the relationship between the antibiotic resistance pattern of bacteria circulating in the community and the consumption of antibiotics in the community.

          Methods

          Both gray literature and published scientific literature in English and other European languages was examined. Multiple regression analysis was used to analyse whether studies found a positive relationship between antibiotic consumption and resistance. A subsequent meta-analysis and meta-regression was conducted for studies for which a common effect size measure (odds ratio) could be calculated.

          Results

          Electronic searches identified 974 studies but only 243 studies were considered eligible for inclusion by the two independent reviewers who extracted the data. A binomial test revealed a positive relationship between antibiotic consumption and resistance (p < .001) but multiple regression modelling did not produce any significant predictors of study outcome. The meta-analysis generated a significant pooled odds ratio of 2.3 (95% confidence interval 2.2 to 2.5) with a meta-regression producing several significant predictors (F(10,77) = 5.82, p < .01). Countries in southern Europe produced a stronger link between consumption and resistance than other regions.

          Conclusions

          Using a large set of studies we found that antibiotic consumption is associated with the development of antibiotic resistance. A subsequent meta-analysis, with a subsample of the studies, generated several significant predictors. Countries in southern Europe produced a stronger link between consumption and resistance than other regions so efforts at reducing antibiotic consumption may need to be strengthened in this area. Increased consumption of antibiotics may not only produce greater resistance at the individual patient level but may also produce greater resistance at the community, country, and regional levels, which can harm individual patients.

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          Most cited references7

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          Testing and adjusting for publication bias

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            Bacterial resistance: origins, epidemiology, and impact.

            The basic mechanisms of antibacterial resistance are well known, but critical new aspects continue to be discovered. Recently discovered factors with major implications for the emergence, dissemination, and maintenance of resistance include multidrug efflux, hypermutability, integrons, and plasmid addiction. Some resistances are widespread and others local, with prevalence rates often worst in newly prosperous countries and in those specialist units where antibacterial use is heaviest. Multidrug-resistant epidemic strains are critical to the total accumulation of resistance (e.g., among Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae), but it remains unclear why some bacterial lineages achieve epidemic spread whereas others that are equally resistant do not. The correlation between in vitro resistance and treatment failure is imperfect, but resistance undoubtedly increases mortality, morbidity, and costs in many settings. Recent concern has led to a plethora of governmental and agency reports advocating less antibacterial use, better antibacterial use, better infection control, and the development of new antibacterials. The evidence that better prescribing can reduce resistance rates is mixed, and although changes to hospital regimens may reduce one resistance problem, other opportunistic bacteria may fill the vacant niche. Overall, the best that can reasonably be anticipated is an improved balance between the accumulation of resistance and new antibacterial development.
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              Antimicrobial Resistance Determinants and Future Control

              At the beginning of the 21st century, antimicrobial resistance is common, has developed against every class of antimicrobial drug, and appears to be spreading into new clinical niches. We describe determinants likely to influence the future epidemiology and health impact of antimicrobial-resistant infections. Understanding these factors will ultimately optimize preventive strategies for an unpredictable future.
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                Author and article information

                Journal
                BMC Infect Dis
                BMC Infect. Dis
                BMC Infectious Diseases
                BioMed Central
                1471-2334
                2014
                9 January 2014
                : 14
                : 13
                Affiliations
                [1 ]Division of Primary Care, University of Nottingham, University Park, Nottingham NG7 2RD, UK
                [2 ]NIVEL (Netherlands Institute for Health Services Research), PO Box 1568, 3500 BN Utrecht, the Netherlands
                [3 ]Department of General Practice and Elderly Care Medicine/EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands
                [4 ]Caphri University of Maastricht/Maastricht, University Hospital, Medical Microbiology, P.Debyelaan 25, 6229 HX Maastricht, the Netherlands
                [5 ]University of Antwerpen, Universitair Ziekenhuis Antwerpen, Laboratory of Medical Microbiology, Wilrijkstraat 10, B-2650 Edegem, Belgium
                Article
                1471-2334-14-13
                10.1186/1471-2334-14-13
                3897982
                24405683
                a1f0bbbd-a433-4727-ac63-77caaa4ff33d
                Copyright © 2014 Bell et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 June 2013
                : 19 December 2013
                Categories
                Research Article

                Infectious disease & Microbiology
                antibiotic resistance,meta-analysis,antibiotic usage,community-acquired infections

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