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      Interventions to Reduce Antibiotic Prescribing in LMICs: A Scoping Review of Evidence from Human and Animal Health Systems

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          Abstract

          This review identifies evidence on supply-side interventions to change the practices of antibiotic prescribers and gatekeepers in low- and middle-income countries (LMICs). A total of 102 studies met the inclusion criteria, of which 70 studies evaluated interventions and 32 provided insight into prescribing contexts. All intervention studies were from human healthcare settings, none were from animal health. Only one context study examined antibiotic use in animal health. The evidence base is uneven, with the strongest evidence on knowledge and stewardship interventions. The review found that multiplex interventions that combine different strategies to influence behaviour tend to have a higher success rate than interventions based on single strategies. Evidence on prescribing contexts highlights interacting influences including health system quality, education, perceptions of patient demand, bureaucratic processes, profit, competition, and cultures of care. Most interventions took place within one health setting. Very few studies targeted interventions across different kinds of providers and settings. Interventions in hospitals were the most commonly evaluated. There is much less evidence on private and informal private providers who play a major role in drug distribution in LMICs. There were no interventions involving drug detailers or the pharmaceutical companies despite their prominent role in the contextual studies.

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          Global increase and geographic convergence in antibiotic consumption between 2000 and 2015

          Significance Antibiotic resistance, driven by antibiotic consumption, is a growing global health threat. Our report on antibiotic use in 76 countries over 16 years provides an up-to-date comprehensive assessment of global trends in antibiotic consumption. We find that the antibiotic consumption rate in low- and middle-income countries (LMICs) has been converging to (and in some countries surpassing) levels typically observed in high-income countries. However, inequities in drug access persist, as many LMICs continue to be burdened with high rates of infectious disease-related mortality and low rates of antibiotic consumption. Our findings emphasize the need for global surveillance of antibiotic consumption to support policies to reduce antibiotic consumption and resistance while providing access to these lifesaving drugs.
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            Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study.

            Resistance to antibiotics is a major public-health problem, and studies that link antibiotic use and resistance have shown an association but not a causal effect. We used the macrolides azithromycin and clarithromycin to investigate the direct effect of antibiotic exposure on resistance in the oral streptococcal flora of healthy volunteers. Volunteers were treated with azithromycin (n=74), clarithromycin (74), or placebo (76) in a randomised, double-blind trial. Pharyngeal swabs were obtained before and after administration of study treatment through 180 days. The proportion of streptococci that were macrolide resistant was assessed and the molecular basis of any change in resistance investigated. Analyses were done on an intent-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00354952. The number of dropouts (n=20) was much the same in all groups until day 42; dropouts increased substantially at day 180 (105). Both macrolides significantly increased the proportion of macrolide-resistant streptococci compared with the placebo at all points studied, peaking at day 8 in the clarithromycin group (mean increase 50.0%, 95% CI 41.7-58.2; p<0.0001) and at day 4 in the azithromycin group (53.4%, 43.4-63.5; p<0.0001). The proportion of macrolide-resistant streptococci was higher after azithromycin treatment than after clarithromycin use, with the largest difference between the two groups at day 28 (17.4% difference, 9.2-25.6; p<0.0001). Use of clarithromycin, but not of azithromycin, selected for the erm(B) gene, which confers high-level macrolide resistance. This study shows that, notwithstanding the different outcomes of resistance selection, macrolide use is the single most important driver of the emergence of macrolide resistance in vivo. Physicians prescribing antibiotics should take into account the striking ecological side-effects of such antibiotics.
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              Factors influencing antibiotic prescribing in China: an exploratory analysis.

              China has very high rates of antibiotic resistance and a health care system that provides strong incentives for over-prescribing. This paper describes the findings of a qualitative study in a province of southern China that seeks to assess knowledge, attitudes, and practices in relation to the use of antibiotics. Semi-structured interviews with patients and health workers at provincial, county, township, and village level. Interviews used four probes (common cold, cough, mild diarrhoea and tiredness) where antibiotics were not indicated, supplemented by questions on knowledge, attitudes, and practices. These data were supplemented by two focus groups, with medical students and pharmacists, and discussions with participants at a national conference on antibiotic use. Coughs and diarrhoea are almost universally treated with antibiotics, while the cold is normally treated with antivirals instead or as well. Many physicians are aware that the cold is usually self-limiting but believe that they can speed recovery and that they are responding to patient expectations. Most physicians and many patients are aware of the phenomenon of antibiotic resistance, although it is often seen as a property acquired by the patient and not the micro-organism. Physicians face financial incentives to prescribe, with profit splitting with pharmaceutical suppliers. Sales profits form a major part of a hospital's income. National guidance on use of antibiotics is fragmentary and incomplete. The misuse of antibiotics poses considerable risks. Effective action will require a multi-faceted strategy including education, based on an understanding of existing beliefs, the replacement of perverse incentives with those promoting best practice, and investment in improved surveillance. Much of this will require action at national level.
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                Author and article information

                Journal
                Antibiotics (Basel)
                Antibiotics (Basel)
                antibiotics
                Antibiotics
                MDPI
                2079-6382
                22 December 2018
                March 2019
                : 8
                : 1
                : 2
                Affiliations
                Institute of Development Studies, University of Sussex, Brighton BN1 NRE, UK; a.ebata@ 123456ids.ac.uk (A.E.); h.macgregor@ 123456ids.ac.uk (H.M.)
                Author notes
                [* ]Correspondence: a.wilkinson@ 123456ids.ac.uk ; Tel.: +44-(0)1273-915-602
                Article
                antibiotics-08-00002
                10.3390/antibiotics8010002
                6466578
                30583566
                cffab018-c01f-49bc-976e-049b03a8418f
                © 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
                : 01 November 2018
                : 18 December 2018
                Categories
                Review

                antibiotic resistance,antibiotic prescribing,antibiotic use,antibiotic stewardship

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