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      Antimicrobial use in an Indonesian community cohort 0-18 months of age

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          Abstract

          Background

          Antimicrobial resistance has become a global health emergency and is contributed to by inappropriate antibiotic use in community clinical settings. The aim of this study was to evaluate the antimicrobial use pattern in infants from birth until 18 months of age in Indonesia.

          Methods

          A post-hoc analysis was conducted in 1621 participants from the RV3BB Phase IIb trial conducted in Indonesia from January 2013 through July 2016. Any health events were documented in the trial as adverse events. Concomitant medication surveillance recorded all medications, including antibiotics during the 18 months of follow-up. Information included the frequency, duration of usage, formulation, classes, and their indications, including prophylactic antibiotic and perinatal use.

          Results

          Of 1621 participants, 551 (33.99%) received at least one antibiotic for treatment of infections during the 18 months observation period. Additionally, during the perinatal period, prophylactic antibiotics were used in 1244 (76.74%) participants and antibiotics consumed in 235 mothers of participants (14.50%). A total of 956 antibiotic consumptions were recorded for 18 months follow up, 67 (7.01%) as part of antimicrobial combinations. The average duration of antibiotic course was 4.92 days. Penicillin and sulfonamides were the most common antibiotic classes consumed (38.81% and 24.48%, respectively).

          Conclusions

          Despite the low community consumption rate, the overuse of antibiotic in URTIs and non-bloody diarrhea in our setting represents a major opportunity for antimicrobial stewardship, particularly in early life.

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          Most cited references46

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          Antibiotic resistance-the need for global solutions.

          The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. Copyright © 2013 Elsevier Ltd. All rights reserved.
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            Association of antibiotics in infancy with early childhood obesity.

            Obesity in children and adults is associated with significant health burdens, making prevention a public health imperative. Infancy may be a critical period when environmental factors exert a lasting effect on the risk for obesity; identifying modifiable factors may help to reduce this risk.
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              Use of antibiotics in children younger than two years in eight countries: a prospective cohort study

              Abstract Objective To describe the frequency and factors associated with antibiotic use in early childhood, and estimate the proportion of diarrhoea and respiratory illnesses episodes treated with antibiotics. Methods Between 2009 and 2014, we followed 2134 children from eight sites in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa and the United Republic of Tanzania, enrolled in the MAL-ED birth cohort study. We documented all antibiotic use from mothers’ reports at twice-weekly visits over the children’s first two years of life. We estimated the incidence of antibiotic use and the associations of antibiotic use with child and household characteristics. We described treatment patterns for diarrhoea and respiratory illnesses, and identified factors associated with treatment and antibiotic class. Findings Over 1 346 388 total days of observation, 16 913 courses of antibiotics were recorded (an incidence of 4.9 courses per child per year), with the highest use in South Asia. Antibiotic treatment was given for 375/499 (75.2%) episodes of bloody diarrhoea and for 4274/9661 (44.2%) episodes of diarrhoea without bloody stools. Antibiotics were used in 2384/3943 (60.5%) episodes of fieldworker-confirmed acute lower respiratory tract illness as well as in 6608/16742 (39.5%) episodes of upper respiratory illness. Penicillins were used most frequently for respiratory illness, while antibiotic classes for diarrhoea treatment varied within and between sites. Conclusion Repeated antibiotic exposure was common early in life, and treatment of non-bloody diarrhoea and non-specific respiratory illnesses was not consistent with international recommendations. Rational antibiotic use programmes may have the most impact in South Asia, where antibiotic use was highest.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – original draft
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administration
                Role: Formal analysisRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: MethodologyRole: Project administrationRole: Validation
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: Project administration
                Role: Investigation
                Role: ConceptualizationRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 August 2019
                2019
                : 14
                : 8
                : e0219097
                Affiliations
                [1 ] Pediatric Research Office, Department of Pediatrics, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Special Region of Yogyakarta, Indonesia
                [2 ] Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Special Region of Yogyakarta, Indonesia
                [3 ] RV3 Rotavirus Vaccine Program, Murdoch Children’s Research Institute, Parkville, Victoria, Australia
                [4 ] Medicines Development for Global Health, Melbourne, Victoria, Australia
                [5 ] Soeradji Tirtonegoro General Hospital, Klaten, Central Java, Indonesia
                [6 ] PT Bio Farma, Bandung, West Java, Indonesia
                [7 ] Department of Pediatrics, University of Melbourne, Melbourne, Victoria, Australia
                [8 ] Department of Gastroenterology and Clinical Nutrition, Royal Children’s Hospital Melbourne, Parkville, Victoria, Australia
                [9 ] Department of Paediatrics, Monash University, Clayton, Victoria, Australia
                [10 ] School of Public Health and Preventive Medicine, Monash University, Clayton, Victoria, Australia
                [11 ] Department of Infection and Immunity, Monash Children’s Hospital, Clayton, Victoria, Australia
                Federal University of Sergipe, BRAZIL
                Author notes

                Competing Interests: The authors have the following interests: NSB is a paid employee of PT Biofarma. PT Biofarma is a state-owned company (owned by Indonesia government) that provides all vaccines for Indonesia National Immunization Program. Additionally, PT Biofarma was one of the funders for the RV3-BB Phase IIB trial. The trial was a phase IIB trial and while the RV3-BB rotavirus vaccine is not yet marketed, this vaccine is being developed with the intention for eventual usage in the national immunization program. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-7035-4846
                http://orcid.org/0000-0002-5452-6601
                Article
                PONE-D-19-08447
                10.1371/journal.pone.0219097
                6681970
                31381611
                a390aeb4-6113-4a58-966e-19916deb81f7
                © 2019 At Thobari 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
                : 25 March 2019
                : 16 June 2019
                Page count
                Figures: 1, Tables: 5, Pages: 15
                Funding
                The vaccine company PT Bio Farma provided support for this study in the form of a salary for the author NSB. The specific role of this author is articulated in the ‘author contributions’ section. Additionally, PT Biofarma was one of the funders of the RV3-BB Phase IIb trial. Another funding source of the RV3-BB Phase IIb trial was Murdoch Children’s Research Institute. The funders had roles in the study design, decision to publish, and preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antimicrobials
                Antibiotics
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobials
                Antibiotics
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antimicrobials
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobials
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Vaccines
                Medicine and Health Sciences
                Public and Occupational Health
                Preventive Medicine
                Prophylaxis
                Antibiotic Prophylaxis
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antimicrobials
                Antibiotics
                Penicillin
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobials
                Antibiotics
                Penicillin
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobial Resistance
                Medicine and Health Sciences
                Pharmacology
                Antimicrobial Resistance
                People and Places
                Population Groupings
                Age Groups
                Children
                Infants
                People and Places
                Population Groupings
                Families
                Children
                Infants
                Research and Analysis Methods
                Research Design
                Clinical Research Design
                Adverse Events
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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