Antimicrobial resistance (AMR) is a serious threat to global public health. WHO emphasises the need for countries to monitor antibiotic consumption to combat AMR. Many low-income and middle-income countries (LMICs) lack surveillance capacity; we aimed to use multiple data sources and statistical models to estimate global antibiotic consumption.In this spatial modelling study, we used individual-level data from household surveys to inform a Bayesian geostatistical model of antibiotic usage in children (aged <5 years) with lower respiratory tract infections in LMICs. Antibiotic consumption data were obtained from multiple sources, including IQVIA, WHO, and the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). The estimates of the antibiotic usage model were used alongside sociodemographic and health covariates to inform a model of total antibiotic consumption in LMICs. This was combined with a single model of antibiotic consumption in high-income countries to produce estimates of antibiotic consumption covering 204 countries and 19 years.We analysed 209 surveys done between 2000 and 2018, covering 284 045 children with lower respiratory tract infections. We identified large national and subnational variations of antibiotic usage in LMICs, with the lowest levels estimated in sub-Saharan Africa and the highest in eastern Europe and central Asia. We estimated a global antibiotic consumption rate of 14·3  defined daily doses (DDD) per 1000 population per day in 2018 (40·2 [37·2–43·7] billion DDD), an increase of 46% from 9·8 (9·2–10·5) DDD per 1000 per day in 2000. We identified large spatial disparities, with antibiotic consumption rates varying from 5·0 (4·8–5·3) DDD per 1000 per day in the Philippines to 45·9 DDD per 1000 per day in Greece in 2018. Additionally, we present trends in consumption of different classes of antibiotics for selected Global Burden of Disease study regions using the IQVIA, WHO, and ESAC-net input data. We identified large increases in the consumption of fluoroquinolones and third-generation cephalosporins in North Africa and Middle East, and south Asia.To our knowledge, this is the first study that incorporates antibiotic usage and consumption data and uses geostatistical modelling techniques to estimate antibiotic consumption for 204 countries from 2000 to 2018. Our analysis identifies both high rates of antibiotic consumption and a lack of access to antibiotics, providing a benchmark for future interventions.Fleming Fund, UK Department of Health and Social Care; Wellcome Trust; and Bill & Melinda Gates Foundation. Bacterial infections are a major cause of morbidity and mortality worldwide. Antibiotics have been hugely successful in improving health outcomes, and alongside improvements in nutrition, clean water, sanitation, and vaccination provision, have aided in the global reduction of under-5 mortality from 216 deaths per 1000 livebirths in 1950 to 39 deaths per 1000 livebirths in 2017, and an increase in male life expectancy from 48 years to 71 years within the same time period.4The relationship between antibiotic use and the development and spread of AMR is well documented.Sustainable Development Goal 3.8 specifies the need for “access to safe, effective, quality and affordable essential medicines and vaccines for all”.11Evidence before this studyDespite some excellent national and regional surveillance systems for antimicrobial consumption, mostly in high-income countries (HICs), large data gaps remain. This is compounded by the fact that the most comprehensive and detailed sources of global antibiotic sales data are proprietary databases. The IQVIA MIDAS database covers 76 countries or territories, including only one low-income country. To identify existing studies estimating global antibiotic consumption we searched PubMed from Jan 1, 1980, to July 28, 2020, for studies using the terms  AND (“consumption” OR “use” OR “usage”) AND  in the title, with no language restrictions.We identified five studies that estimated global antibiotic consumption, four of these were published in the past 10 years and were based entirely on the IQVIA MIDAS database, with the two most recent studies following the WHO Anatomical Therapeutic Chemical (ATC) classification/defined daily doses (DDD) methodology. Additionally, several studies were identified that focused on analysing the consumption of child-appropriate oral formulations of antibiotics using the IQVIA MIDAS database. The most comprehensive study estimated global antibiotic consumption from 2000 to 2015 and calculated consumption for the 76 countries or territories covered by the dataset, extrapolating the rates of consumption to the global population. However, the study did not provide estimates of antibiotic consumption for individual countries not covered by the IQVIA dataset.Our searches for global antibiotic usage identified one study estimating caregiver-reported antibiotic usage in children (aged <5 years) with fever, diarrhoea, or cough with difficulty breathing in low-income and middle-income countries (LMICs). The study used Demographic Health Survey and Multiple Indicator Cluster household data; estimates were stratified by WHO region. The study did not produce estimates of antibiotic usage for individual countries and districts.Added value of this studyWe provide the first estimates of longitudinal human antibiotic consumption (ATC J01) for 204 countries from 2000 to 2018, using a novel approach that applied spatial modelling techniques and incorporated multiple data sources, including large-scale antibiotic usage surveys. We used the most recent version of the WHO ATC/DDD guideline and index with higher DDD values for key antibiotics such as ampicillin and amoxicillin. We estimate that the global volume of antibiotic consumption was 40·2  billion DDD in 2018, an increase of 46% since 2000. Antibiotic consumption in 2018 was inequitable between HICs and LMICs, with respective rates of 20·6 DDD and 13·1 DDD per 1000 population per day.Rates of antibiotic consumption varied by nearly a factor of 10, highlighting the lack of access to essential antibiotics as well as overuse. We also present trends in consumption of different classes of antibiotics using the IQVIA, WHO, and European Surveillance of Antimicrobial Consumption Network (ESAC-Net) input data. Additionally, we provide detailed subnational estimates of community-based antibiotic usage in children with lower respiratory tract infections in LMICs (135 countries), from 2000 to 2018. Our study highlights the substantial variation in antibiotic usage between LMICs and the high inequalities within some countries.Implications of all the available evidenceInsights from longitudinal antibiotic consumption surveillance within a country are essential for implementing and monitoring policy to tackle inappropriate antibiotic use. Addressing lack of access as well as inappropriate antibiotic use is crucial for tackling the growing threat of antimicrobial resistance and ensuring fair and equitable access to essential medicines for all.Despite some excellent national and regional surveillance systems,This study aims to estimate global antibiotic consumption using two different types of data: first, antibiotic consumption data, referring to the aggregated amount of antibiotics consumed by a country, derived from national sales and import and reimbursement databases, obtained from multiple sources; and second, antibiotic usage data, referring to the use of antibiotics by individual patients,We modelled antibiotic consumption in HICs and LMICs separately due to differing covariate effects and data availability . For LMIAntibiotic usage data were extracted from household surveys, primarily the United States Agency for International Development's Demographic Health Surveys (DHS) and UNICEF's Multiple Indicator Cluster Surveys MICS; . These lData on the proportion of children (aged <5 years) with symptoms of lower respiratory tract infection in the previous 2 weeks who received antibiotics, for the time period from 2000 to 2018, were extracted and linked to the smallest geographical location available: global positioning system cluster coordinates (point locations) or administrative districts (hereafter administrative level 1 areas will be referred to as states and administrative level 2 areas as districts). Administrative districts were resampled to point locations using population weighted K-means clusteringWe used a two-stage Bayesian hierarchical model, established for fine scale mapping of health outcomesAntibiotic usage was not estimated for North Korea or island nations with populations under 100 000 people due to a lack of sufficient survey data, covariates, and geographical contiguity. For these countries, national estimates were inferred as the median antibiotic usage for that region. Finally, we analysed the within-country variation in antibiotic usage by calculating the relative deviation of antibiotic usage in each district from the country mean , and summarising at the national level by calculating the range of these relative deviations.We obtained antibiotic consumption data from IQVIA for 76 countries and territories from 2000 to 2018. Data were provided in two datasets; 2000–13 (IQVIA MIDAS) data were provided as standard units for each product of J01 class antibiotics , and data for 2014–18  were provided in kilograms, aggregated for each J01 class antibiotic (regardless of product or preparation); we have referred to the combined data as the IQVIA dataset. Data were provided disaggregated by hospital and retail sectors.We restricted the dataset to antibiotics for systemic use . Standard units (for 2000–13) were converted to kilograms and defined daily doses (DDD) calculated for each antibiotic following the latest versions of the WHO Collaborating Centre for Drug Statistics Methodology and ATC/DDD index  countries contained only data from the retail sector; for these data points the values for antibiotic consumption in hospitals were imputed using classification and regression trees (CART) multiple imputation method from the MICE package (version 3.7.0) in R (version 3.6.1). The data for all J01 antibiotics consumed in hospital and retail sectors were aggregated to provide one value for total consumption per country year.Global Burden of Disease (GBD) study. The final dataset covered 47 (68%) of 69 HICs and 65 (48%) of 135 LMICs.Additional sources of national antibiotic consumption data from which DDD were calculable for countries and years not included in the IQVIA datasets were obtained from the WHO report on surveillance of antibiotic consumption (referred to as the WHO dataset), which contains consumption data from 65 countries for 2015–16;Data coverage for HICs was high (99·2% population coverage); countries with missing data  were genFor LMICs, data coverage was sparser than for HICs (78·3% population coverage). To account for this sparsity of data and to leverage the estimates of antibiotic usage in LMICs, we used a two-stage modelling framework to estimate antibiotic consumption (in DDD per 1000 population) for each LMIC from 2000 to 2018. The estimates of antibiotic usage prevalence, aggregated to the national level, were used as a covariate  to fit a stacked ensemble model. Stacking has been shown to improve predictive validity compared with non-ensemble modelling methodologies, to aid with covariate selection and to account for non-linearity and interactions between covariates.The estimates of antibiotic consumption in LMICs and HICs were combined to present global antibiotic consumption in DDD per 1000 population per day for each year, from 2000 to 2018. Uncertainty for the LMIC antibiotic consumption model was estimated by taking 1000 draws of the Gaussian process regression and calculating the 95% UIs. Uncertainty was not calculated for HICs due to the differing modelling strategies.A spatial-temporal modelling approach to estimate consumption by antibiotic class was deemed inappropriate, due to the lack of spatial trends and association to health and sociodemographic covariates for the data. Antibiotic consumption for each class of antibiotics (ATC level 3 and select ATC level 4 classes) and WHO AWaRe categoriesThe funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.Nuffield Department of Medicine's website. Results showed high spatial variability in our estimates of antibiotic usage, both between and within countries.From 2000 to 2018, data from 209 surveys and 284 045 children (aged <5 years), covering 101 countries and 19 years, were input into the model of antibiotic usage in LMICs , with national estimates highest in Ukraine , Kazakhstan , Bosnia and Herzegovina , and Belarus , with high usage estimated in Vietnam  and Malaysia , whereas Papua New Guinea , Philippines , and Indonesia  were notably lower.From 2000 to 2018, the prevalence of antibiotic usage was consistently low in sub-Saharan Africa and consistently high in eastern Europe and central Asia . HoweverWe identified high inequalities in antibiotic usage within countries; in 2018, the relative deviation in antibiotic usage was highest in India and Laos (both 51% relative deviation). In sub-Saharan Africa, the relative deviation in antibiotic usage was highest in Nigeria (46%) and Benin (40%). Four countries in sub-Saharan Africa  were home to the 50 districts with the lowest proportion of antibiotic usage. Overall, there was little difference in the relative deviation in antibiotic usage between 2000 and 2018; however, decreases were noted in India (73% to 51%), Indonesia (63% to 25%), and Cambodia  billion DDD in 2018, equating to a rate of 14·1 (13·2–15·6) DDD per 1000 population per day . Antibiotic consumption was inequitable between World Bank classified HICs and LMICs, with respective rates of 20·6 DDD per 1000 per day and 13·1 (95% UI 11·8–14·6) DDD per 1000 per day . South AWe identified large spatial disparities in the rates of antibiotic consumption, with the rates in Greece (45·9 DDD per 1000 per day) and Tunisia (38·0 [95% UI 36·0–40·2] DDD per 1000 per day) almost ten times higher than the lowest rates found in countries such as the Philippines (5·0 [4·8–5·3]), Honduras (5·6 [5·4–5·9]), Burundi (5·3 [4·3–6·4]), and Central African Republic  DDD per 1000 per day in 2000 to 14·3 (13·2–15·6) in 2018. This differed greatly between HICs and LMICs; although consumption rates remained stable in HICs across the study period (20·8 DDD per 1000 per day in 2000 compared to 20·6 in 2018), there was a 76% increase observed in LMICs  with lower respiratory tract infections in LMICs from 2000 to 2018. We identified large variations in the proportion of children with reported antibiotic use across and within LMICs. In 2018, the highest levels of antibiotic usage were estimated in the central Europe, eastern Europe, and central Asia super-region (median antibiotic usage of 72%), and the lowest levels for sub-Saharan Africa (median antibiotic usage 43%). Our subnational estimates highlight inequalities in antibiotic usage within countries, underlining issues of access to health care, particularly in poor and rural communities. A recent studyWe identified not only large variations in the rates of total antibiotic consumption across countries, but also in the proportion of antibiotics classes used in different geographical contexts.32The main limitations of our modelling study are centred around data quality and availability issues. Data on antibiotic usage in LMICs are sparse, with most studies focusing on the knowledge, attributes, and practices of antibiotic usage in specific study locations.Another limitation stems from the fact that we used antibiotic usage in children (aged <5 years) to model antibiotic consumption in the general population in LMICs, assuming that the spatial–temporal trends in antibiotic usage between adults and children were comparable. High antibiotic usage in adults is corroborated by health-care utilisation surveys done in LMICs that show a strong trend for adults to access community pharmacies as first point of contact and to self-medicate with over-the-counter antibiotics;56The IQVIA MIDAS database is a proprietary database, restricting access and analysis. For the 24 included countries lacking data from hospitals, we relied on multiple imputation methods to estimate total antibiotic consumption. Additionally, for some countries, such as India, the IQVIA MIDAS hospital data exclude public facilities, which could underestimate consumption. Only formal channels of antibiotic sales are included in IQVIA MIDAS; therefore sales of antibiotics from informal markets, which could make up a considerable proportion of antibiotic sales in LMICs,The lack of antibiotic consumption data in LMICs is another limitation. Our combined dataset only covers 48% of LMICs, highlighting the urgent need for the establishment of antibiotic consumption surveillance programmes,To our knowledge, our study provides the first longitudinal antibiotic consumption estimates for 204 countries from 2000 to 2018, presenting an important benchmark of antibiotic consumption and highlighting spatial disparities in antibiotic usage and consumption. We identified countries with very high antibiotic consumption, indicating excess use, and countries with very low consumption, indicative of a lack of access to essential antibiotics. These findings underline the scope and potential major benefits of antibiotic stewardship interventions, aided by antibiotic consumption surveillance,www.ndm.ac/gram-project/antibiotic-consumption.The source code for all analysis is available at https://github.com/NDM-GRAM/Antibiotic-consumption. Interactive data visualisations and all estimates, including antibiotic usage estimates aggregated to national, state, and district levels, and antibiotic consumption estimates for total J01 antibiotic consumption, consumption by ATC level 3 classes, and consumption by select ATC level 4 classes are available at AS has been the recipient of research grants from the Bill & Melinda Gates Foundation. All other authors declare no competing interests.


Background: Antimicrobial resistance is a significant clinical problem in pediatric practice in China. Surveillance of antibiotic use is one of the cornerstones to assess the quality of antibiotic use and plan and assess the impact of antibiotic stewardship interventions.Methods: We carried out quarterly point prevalence surveys referring to WHO Methodology of Point Prevalence Survey in 16 Chinese general and children’s hospitals in 2019 to assess antibiotic use in pediatric inpatients based on the WHO AWaRe metrics and to detect potential problem areas. Data were retrieved via the hospital information systems on the second Monday of March, June, September and December. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions and ward types according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) Classification.Results: A total of 22,327 hospitalized children were sampled, of which 14,757 (66.1%) were prescribed ≥1 antibiotic. Among the 3,936 sampled neonates (≤1 month), 59.2%  were prescribed ≥1 antibiotic. A high percentage of combination antibiotic therapy was observed in PICUs (78.5%), pediatric medical wards (68.1%) and surgical wards (65.2%). For hospitalized children prescribed ≥1 antibiotic, the most common diagnosis on admission were lower respiratory tract infections . WHO Watch group antibiotics accounted for 70.4% of prescriptions . The most prescribed antibiotic ATC classes were third-generation cephalosporins , followed by penicillins/β-lactamase inhibitors , macrolides  and carbapenems .Conclusion: Based on these data, overuse of broad-spectrum Watch group antibiotics is common in Chinese pediatric inpatients. Specific interventions in the context of the national antimicrobial stewardship framework should aim to reduce the use of Watch antibiotics and routine surveillance of antibiotic use using WHO AWaRe metrics should be implemented. Klebsiella pneumoniae and Acinetobacter baumannii is 13.4 and 28.5% in children’s hospital, highlighting the growing challenge of treating pediatric infectious diseases in China -producing Enterobacteriaceae is >50%. The carbapenem resistance in in China .Appropriate use of antibiotics is fundamental to slow the emergence and spread of antibiotic resistance and extend the useful lifetime of existing antibiotics . In 2015Recognizing the need for practical tools for antibiotic stewardship at the national and international levels to assess and supervise the appropriate use of antibiotics, WHO updated the Model List of Essential Medicines for Children (EMLc) in 2017 and grouped antibiotics into three main categories——Access, Watch, and Reserve (AWaRe) . Access n = 21,324) were from tertiary care hospitals and 4.5%  were from secondary care hospitals; 92.0%  were from specialized children’s hospitals and 8.0%  were from pediatric wards of general hospitals. Of 22,327 pediatric inpatients, 17.6% were neonates (0 to <1 month) and 42.3% were children ≤1 year  were excluded based on the pre-specified inclusion/exclusion criteria and 22,327 (94.4%) were eligible for the final analysis. Of the eligible patients, 95.5%  and 66.0%  in male and female inpatients. The percentage of patients receiving antibiotics was higher in secondary care hospitals  than in tertiary care hospitals ; antibiotics were prescribed most frequently in children aged 1 month to <1 year (71.6%). Of the 14,757 patients in which antibiotics prescribed, percentages of inpatients receiving intravenous antibiotic therapy and combination antibiotic therapy ranged from 72.5 to 100%  and 7.8–41.8%  within the 16 participating hospitals, respectively  received ≥1 antibiotic prescription, of which, 6,275 (42.5%) were neonates and 9,430 (63.9%) were children younger than 3 years. The percentage of children receiving antibiotic therapies varied by hospitals  and age groups . The percentage of patients receiving antibiotics was 66.2% , azithromycin , cefperazone/sulbactam , cefotaxime  and piperacillin/tazobactam . Meropenem accounted for 5.7%  of all prescribed antibiotics. Amoxicillin and amoxicillin/clavulanic acid accounted for 0.9% (n = 160) and 5.0% (n = 919) of all antibiotic therapies, respectively. The most prescribed antibiotic ATC classifications were third-generation cephalosporins , penicillin/β-lactamase inhibitors , macrolides  and carbapenems . Third-generation cephalosporins were the most commonly prescribed antibiotics in 16 participating hospitals and all age groups. Piperacillin/tazobactam and amoxicillin/clavulanic acid were the most common penicillin/β-lactamase inhibitors combination, followed by ampicillin/sulbactam (n = 332), mezlocillin/sulbactam (n = 242), piperacillin/sulbactam (n = 59) and amoxicillin/sulbactam (n = 35).A total of 18,344 antibiotic prescriptions including 69 different antibiotic agents were assessed at the surveyed points. The five most commonly prescribed antibiotic agents were ceftazidime  and 648 (4.4%) inpatients were prescribed with third-generation cephalosporins-based and carbapenem-based combination antibiotic therapy, respectively. The most common combination antibiotic therapy was third generation cephalosporins in combination with macrolides .n = 2,664), 70.4%  and 1.5% (n = 266), respectively. The percentage of Access and Watch antibiotics ranged from 2.5 to 49.0%  and 30.1–89.4%  among 16 participating hospitals. Reserve group antibiotics were used in 12 tertiary hospitals and accounted for less than 5% in each hospital . The percentage of Access antibiotics was less than 25% in all age groups while Watch antibiotics accounted for 55.7–74.3% among different age groups.According to WHO AWaRe classification, Access, Watch and Reserve antibiotics accounted for 14.5% . Combination antibiotic therapy was common in patients with a diagnosis of lower respiratory tract infections  of Watch antibiotics and 34.8% (n = 464) of carbapenems were prescribed for patients with a diagnosis of lower respiratory tract infection on admission.Of the 14,757 hospitalized children in which antibiotics were prescribed, the most common diagnostic condition on admission was lower respiratory tract infections (fections . Of noten = 928) and 73.8% , respectively. Watch antibiotics were the most prescribed antibiotics (54.4–92.4%) among 11 hospitals. According to ATC classification, third-generation cephalosporins (46.6%) were the most prescribed antibiotics, followed by macrolides (20.5%) and penicillin/β-lactamase inhibitors (16.2%). The percentage of carbapenems was 5.5% and even >10% among three participating hospitals. The percentage of penicillins/β-lactamase inhibitors was >50% in one hospital (S3).For children with a diagnosis of lower respiratory tract infection on admission, the percentage of WHO Access and Watch antibiotics were 11.4% (n = 64) was the most prescribed antibiotic agent, followed by ampicillin/sulbactam  and ceftazidime .There were 850 antibiotic therapies prescribed for children with a diagnosis of sepsis on admission, in which, third-generation cephalosporins (34.8%) were the most prescribed antibiotics, followed by carbapenems (20.4%) and penicillins/β-lactamase inhibitors (14.1%). Besides, 300 (35.3%) antibiotic therapies were used for neonates, in which, meropenem , pediatric medical wards (68.1%) and surgical wards (65.2%). The percentage of antibiotic prescribing  and distThe most obvious variation of antibiotic prescribing patterns was seen in neonatal wards among hospitals. The overall percentage of antibiotic prescriptions in neonatal wards were 59.7%, ranging from 19.1 to 88.3%  among hospitals. The percentages of Access and Watch antibiotics were 23.2 and 61.9% in neonatal wards, ranging from 2.8 to 56.7%  and 24.3–89.4%  among hospitals, respectively. In all, third-generation cephalosporins (39.4%) were the most commonly prescribed antibiotic category, followed by penicillins/β-lactamase inhibitors (26.0%) and carbapenems (9.5%). The percentage of carbapenems ranged from 1.1 to 24.2%  among hospitals.For children hospitalized in PICUs of the 11 hospitals, lower respiratory tract infections (49.8%) were the most common diagnosis on admission. The percentage of children on antibiotic therapy ranged from 62.5 to 95.2% . Generally, third-generation cephalosporins (35.5%) and carbapenems (18.7%) were frequently prescribed antibiotic ATC classes in PICUs. In three hospitals, the percentage of carbapenems prescription was higher than 30%.n = 293), lower respiratory tract infections  and skin and soft tissue infections . Generally, third-generation cephalosporins  and second-generation cephalosporins  were the most prescribed antibiotic ATC classes in surgical wards.For children hospitalized in surgical wards of the 13 hospitals, the percentage of children on antibiotic therapy was 65.2%, ranging from 62.5 to 95.2%. For patients on antibiotic therapy, 40.1% had a diagnosis related to infectious conditions on admission, in which, the common diagnoses were abdominal infections , sulfonamids and trimethoprim  and carbapenems  were the frequently prescribed antibiotic ATC classes.For children hospitalized in high risk wards of seven hospitals, the percentage of children on antibiotic therapy was 63.6%, ranging from 33.3 to 77.4% . For children on antibiotic therapy, 66.1 and 41.8% had a diagnosis of either high risk disease or infectious disease on admission, respectively. Generally, third-generation cephalosporins , Australia (46%) and the United States(42.6%) , but wasOur study noticed a significant variation in antibiotic use even across similar medical settings and within ward types in China. The point prevalence of antibiotic use ranged from 36.8 to 94.2% in 16 participating hospitals, from 19.1 to 88.3% in neonatal wards and from 35.3 to 94.4% in surgical wards. We also observed a substantial variation between hospitals in the use of Access, Watch, and Reserve antibiotics within ward types and diagnostic conditions. In the 15 neonatal wards, the percentage of Access and Watch group antibiotics ranged from 2.8 to 56.7% and from 24.3 to 89.4%, respectively. This situation in fact reflects inconsistency in antibiotic prescribing behavior and the poor compliance of the guidelines on common infectious diseases among pediatricians. Thus, there is an urgent need to implement standardized clinical pathways or guidelines of common infectious diseases and strengthening education to improve appropriate use of antibiotic.Escherichia coli (E.coli) and Klebsiella pneumoniae among blood stream infection was 36.0 and 56.7%, respectively   , which iE. coli and Klebsiella pneumoniae is 0.6 and 6.5% in pediatric patients  and Australia (3.2%) . For chipatients . So far,patients . The Chipatients . ImproviThe study has several strengths. First, we applied comprehensive and child-appropriate indications based on WHO AWaRe methodology to assess the appropriateness of pediatric antibiotic prescribing. Second, we adopted standardized methodology of point prevalence survey and a large sample size to reduce the bias of surveillance data. Third, we compared the variation in antibiotic prescribing practice among hospitals and by ward types.The study also has a few of limitations. First, the appropriateness of antibiotic prescribing could not be determined based on the detailed patient characteristics, indication of antibiotic use, severity of infection, duration of therapy, or microbiology and antimicrobial susceptibility results. Second, most of participating hospitals in this study were provincial or municipal tertiary hospitals on a voluntary basis, thus, our results cannot fully represent the current situation of antibiotic use in secondary hospitals and county hospitals in China. However, our surveillance data remain representative and reflected the objective situation and issues on antibiotic use in Chinese pediatric inpatients because the majority of pediatric inpatients are hospitalized in the tertiary hospitals in China. The results provided useful information for pediatricians to improve clinical practice and for policy-makers to strengthen the pediatric antimicrobial stewardship in the future.This study is designed prospectively to retrieve point prevalence surveys (PPS) of antibiotic use in hospitalized children in China referring to WHO Methodology of Point Prevalence Survey on Antibiotic Use in Hospitals . SixteenAll neonates and pediatric patients were included in the survey if they met the following criteria: younger than 16 years of age, present in the ward at 8:00 a.m. on the day of the survey and having been hospitalized in specialized pediatric wards for at least 24 h.All data were retrieved via the hospital information system and finally reviewed by two infectious diseases specialists to exclude invalid or incomplete records. The exclusion criteria for sampled patients were as the following: 1) patients hospitalized in emergency observational wards, rehabilitation wards, and daycare wards; 2) hospitalized patients with incomplete information about patient’s demographics, diagnoses or medication.Patient demographic data were collected for all surveyed patients, irrespective of antibiotic treatment. Antibiotic data were collected for patients on antibiotic therapy and included information on the antibiotics prescribed, such as the type of antibiotics, route of administration and the diagnoses on admission. Reason for prescribing antibiotics was not routinely available via hospital information systems. Therefore, we assessed the antibiotic prescribing roughly based on admission diagnoses.In this study, “pediatric wards” were grouped into pediatric medical ward, pediatric surgical ward, pediatric intensive care unit (PICU), neonatal ward, neonatal intensive care unit (NICU) and high-risk ward. “High-risk wards” included hematology and oncology wards. “Antibiotics” included antibacterial agents for systemic use listed in the Anatomical Therapeutic Chemical (ATC) class J01 and orally administered metronidazole (P01AB01). In addition, cefathiamidine (J01DBX) and kitasamycin (J01FAX) which are not included in the WHO ATC classification were coded according to the pharmacological characteristics and the classification rules of the ATC guideline . Antibio1.the percentage of hospitalized children in which >1 antibiotic was prescribed was calculated by dividing the number of hospitalized children prescribed ≥1 antibiotics by the total number of hospitalized children and multiplying by 100;2.the percentage of hospitalized children in which ≥1 intravenous antibiotic was prescribed was calculated by dividing the number of hospitalized children prescribed ≥1 intravenous antibiotics by the total number of hospitalized children prescribed antibiotics and multiplying by 100;3.the percentage of hospitalized children in which combination antibiotic therapy was prescribed was calculated by dividing the number of hospitalized children prescribed >1 antibiotics by the total number of hospitalized children prescribed ≥1 antibiotic and multiplying by 100;4.the percentage of antibiotics prescribed in each ATC class or WHO AWaRe category was calculated by dividing the number of antibiotic prescriptions prescribed in a certain ATC class or AWaRe category by the total number of antibiotics prescriptions prescribed and multiplying by 100.The following antibiotic prescribing indicators were calculated:These indicators were calculated separately for each hospital, ward type, diagnostic condition and age group .All data were exported into an Excel spreadsheet. Descriptive analyses were conducted by using Excel , Access  and GraphpadPrism .Ethics approval was received for all participating hospitals from their respective institutional human research ethics committees. Informed consent from patients was not required by the ethics committee because there was no contact with patients and all data were de-identified.


Esophageal cancer is a highly malignant cancer with a very poor prognosis. For resectable esophageal cancer, neoadjuvant treatment could improve the prognosis of esophageal cancer. However, current clinical neoadjuvant treatment options for esophageal cancer are still limited. The application of immunotherapy is a potentially beneficial new neoadjuvant treatment option for esophageal cancer. The objective of this meta-analysis is to evaluate the efficacy and safety of immunotherapy for the neoadjuvant treatment of esophageal cancer.We will search Wanfang Database, SinoMed, China National Knowledge Infrastructure, Embase, Web of Science, Pubmed, and Cochrane Library for relevant articles published before July, 2021. We will also search the unpublished clinical trials of neoadjuvant immunotherapy in esophageal cancer in preprint website (such as bioRXiv and medRxiv) up to July, 2021. We will perform a meta-analysis to evaluate the efficacy and safety of neoadjuvant immunotherapy for resectable esophageal cancer. Randomized controlled trials (RCTs) will be included in this study. The risk of bias will be evaluated for each included study using the Cochrane Handbook for Systematic Reviews of Interventions. We will use RevMan 5.3 software for statistical analysis of the data.The results of this study will provide evidence of immunotherapy using as neoadjuvant treatment for esophageal cancer. This meta-analysis will be submitted to a peer-reviewed journal seeking for publication.The results of this study will provide a reliable basis for clinicians and patients to formulate the best pre-surgical treatment plan for resectable esophageal cancer.INPLASY202120026. Esophageal cancer is one of the most common malignant tumors , and hasSurgery is still the radical treatment for esophageal cancer . HoweverIn recent years, immunotherapy has opened up a whole new field for the treatment of esophageal cancer , 14. SevThe preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement will be followed to conducted this protocol . The finWe will search Wanfang Database, SinoMed, China National Knowledge Infrastructure (CNKI), Embase, Web of Science, Pubmed, and Cochrane Library for relevant articles that may be eligible for inclusion published before July, 2021. We will also identify other articles from the review’s references that meet the criteria. We will also search the unpublished clinical trials of neoadjuvant immunotherapy in esophageal cancer in preprint website (such as bioRXiv and medRxiv) up to July, 2021.The two reviewers (Guocan Yu and Wenfeng Yu) will use the keywords or subject terms corresponding to medical subject heading (MeSH) terms to design search strategies for each database and perform searches in each database to identify eligible articles. No language restrictions will be applied in the search process. The search strategies for PubMed are showed as follows:#1 "Immunotherapy"[Mesh] OR Immunotherapies OR#2 "Programmed Cell Death 1 Receptor"[Mesh] OR “PD-1 Protein” OR “PD 1 Protein” OR “PD-1 Receptor” OR “PD 1 Receptor” OR “Receptor, PD-1” OR “Antigens, CD279” OR “CD279 Antigens” OR “CD279 Antigen” OR “Antigen, CD279” OR “PD1 Receptor” OR “Receptor, PD1” OR “Programmed Cell Death Protein 1” OR “Programmed Cell Death 1 Protein”#3 "Immune Checkpoint Inhibitors"[Mesh] OR “Checkpoint Inhibitors, Immune” OR “Immune Checkpoint Inhibitor” OR “Checkpoint Inhibitor, Immune” OR “Immune Checkpoint Blockers” OR “Checkpoint Blockers, Immune” OR “Immune Checkpoint Blockade” OR “Checkpoint Blockade, Immune” OR “Immune Checkpoint Inhibition” OR “Checkpoint Inhibition, Immune” OR “PD-L1 Inhibitors” OR “PD L1 Inhibitors” OR “PD-L1 Inhibitor” OR “PD L1 Inhibitor” OR “Programmed Death-Ligand 1 Inhibitors” OR “Programmed Death Ligand 1 Inhibitors” OR “CTLA-4 Inhibitors” OR “CTLA 4 Inhibitors” OR “CTLA-4 Inhibitor” OR “CTLA 4 Inhibitor” OR “Cytotoxic T-Lymphocyte-Associated Protein 4 Inhibitors” OR “Cytotoxic T Lymphocyte Associated Protein 4 Inhibitors” OR “Cytotoxic T-Lymphocyte-Associated Protein 4 Inhibitor” OR “Cytotoxic T Lymphocyte Associated Protein 4 Inhibitor” OR “PD-1 Inhibitors” OR “PD 1 Inhibitors” OR “PD-1 Inhibitor” OR “Inhibitor, PD-1” OR “PD 1 Inhibitor” OR “Programmed Cell Death Protein 1 Inhibitor” OR “Programmed Cell Death Protein 1 Inhibitors” OR “PD-1-PD-L1 Blockade” OR “Blockade, PD-1-PD-L1” OR “PD 1 PD L1 Blockade”#4 #1 OR #2 OR #3#5 "Esophageal Neoplasms"[Mesh] OR “Esophageal Neoplasm” OR “Neoplasm, Esophageal” OR “Esophagus Neoplasm” OR “Esophagus Neoplasms” OR “Neoplasm, Esophagus” OR “Neoplasms, Esophagus” OR “Neoplasms, Esophageal” OR “Cancer of Esophagus” OR “Cancer of the Esophagus” OR “Esophagus Cancer” OR “Cancer, Esophagus” OR “Cancers, Esophagus” OR “Esophagus Cancers” OR “Esophageal Cancer” OR “Cancer, Esophageal” OR “Cancers, Esophageal” OR “Esophageal Cancers”#6 "Neoadjuvant Therapy"[Mesh] OR “Neoadjuvant Therapies” OR “Therapy, Neoadjuvant” OR “Neoadjuvant Treatment” OR “Neoadjuvant Treatments” OR “Treatment, Neoadjuvant” OR “Neoadjuvant Radiotherapy” OR “Neoadjuvant Radiotherapies” OR “Radiotherapy, Neoadjuvant” OR “Neoadjuvant Radiation Treatment” OR “Neoadjuvant Radiation Treatments” OR “Radiation Treatment, Neoadjuvant” OR “Treatment, Neoadjuvant Radiation” OR “Neoadjuvant Radiation Therapy” OR “Neoadjuvant Radiation Therapies” OR “Radiation Therapy, Neoadjuvant” OR “Therapy, Neoadjuvant Radiation” OR “Neoadjuvant Radiation” OR “Neoadjuvant Radiations” OR “Radiation, Neoadjuvant” OR “Neoadjuvant Systemic Therapy” OR “Neoadjuvant Systemic Therapies” OR “Systemic Therapy, Neoadjuvant” OR “Therapy, Neoadjuvant Systemic” OR “Neoadjuvant Systemic Treatment” OR “Neoadjuvant Systemic Treatments” OR “Systemic Treatment, Neoadjuvant” OR “Treatment, Neoadjuvant Systemic” OR “Neoadjuvant Chemotherapy” OR “Chemotherapy, Neoadjuvant” OR “Neoadjuvant Chemotherapies” OR “Neoadjuvant Chemotherapy Treatment” OR “Chemotherapy Treatment, Neoadjuvant” OR “Neoadjuvant Chemotherapy Treatments” OR “Treatment, Neoadjuvant Chemotherapy” OR “Neoadjuvant Chemoradiotherapy” OR “Chemoradiotherapy, Neoadjuvant” OR “Neoadjuvant Chemoradiotherapies” OR “Neoadjuvant Chemoradiation Therapy” OR “Chemoradiation Therapy, Neoadjuvant” OR “Neoadjuvant Chemoradiation Therapies” OR “Therapy, Neoadjuvant Chemoradiation” OR “Neoadjuvant Chemoradiation Treatment” OR “Chemoradiation Treatment, Neoadjuvant” OR “Neoadjuvant Chemoradiation Treatments” OR “Treatment, Neoadjuvant Chemoradiation” OR “Neoadjuvant Chemoradiation” OR “Chemoradiation, Neoadjuvant” OR “Neoadjuvant Chemoradiations” OR “pre-surgical” OR “presurgical” OR “pre-operative” OR “preoperative” OR neoadjuvant#7 #4 AND #5 AND #6The SinoMed, Wanfang Database, CNKI, Embase, and Cochrane Library search strategies will be similar to Pubmed.Clinical randomized controlled trials (RCTs), which must have been completed and evaluated the efficacy and safety of neoadjuvant immunotherapy in resectable esophageal cancer. Reviews, repeated publications, articles published not using Chinese or English, studies with less than 10 patients, and case reports will be excluded.Participants with resectable esophageal cancer confirmed by histopathology or cytopathology and immune checkpoint inhibitors (ICIs) were used as neoadjuvant therapy. There will be no restrictions on age, gender, and ethnicity.Immunotherapy  alone or immunotherapy plus other therapy as neoadjuvant treatment for resectable esophageal cancer.Other treatments (not include immunotherapy) as neoadjuvant therapy for resectable esophageal cancer (not mandatory).Major pathological response (MPR), pathological complete response (pCR), the incidence of TRAE, surgical resection rate, the incidence of surgical complications, and surgical delay rate will be the key clinical outcomes.Endnote X9.2 software will be used to manage the articles obtained by searching the relevant databases. In the first step, two reviewers (Guocan Yu and Wenfeng Yu) will independently filter duplicate articles through Endnote and exclude them, then exclude articles that do not meet the inclusion criteria by investigating the title and abstract, and finally screen the full text of remaining articles to finalize the eligible articles. If there are disagreements between the two reviewers, a discussion with the third reviewer (Liwei Yao) will be conducted as a way to resolve the disagreements.The same two reviewers (Guocan Yu and Wenfeng Yu) as in the study selection phase will independently extract the necessary data from the articles included. Cross-check will be done to find controversial data and resolve by discussing with a third author (Liwei Yao).The following data from the included articles will be extracted: first author name, year of publication, countries, article type, clinical trial, registration number, study phase, masking, main inclusion criteria, type of pathology, the ICI drug, ICIs dose, programmed cell death-ligand-1 [PD-L1]/ programmed cell death 1 [PD-1] expression levels in tumoral and immune cells, expected inclusion, size of sample, male, median age, MPR, pCR, incidence of TRAE, surgical resection rate, incidence of surgical complication, and surgical delay rate.Two authors (Guocan Yu and Wenfeng Yu) will independently assess the risk of bias of each article included. The Cochrane Handbook for Systematic Reviews of Interventions will be used for the evaluation of the risk of bias . We willP-value of the Q-statistic < 0.1 or an I2 > 50% will be considered as statistically significant heterogeneity between studies [P < 0.05 was considered statistically different.We will use Review Manager software, version 5.3  for statistical analysis of the meta-analysis. We will calculate pooled risk ratios (HRs) for MPR, pCR, incidence of TRAE, surgical resection rate, incidence of surgical complication, and surgical delay rate with comparative binary data in RevMan 5.3. HR with 95% confidence interval (CI) will be the effect measures. The statistical heterogeneity between studies will be evaluated by the Q-statistic . The P-v studies . Data wi studies . A P < 0When significant heterogeneity exists and sufficient data are available, we will conduct subgroup analysis to further explore the sources of heterogeneity. We will conduct subgroup analysis of each parameter , when the extracted data are sufficient.Sensitivity analysis will be conducted to evaluate the reliability and robustness of the aggregation results via eliminating studies with high bias risk.We will use funnel plots and Egger test to assess publication bias when more than 10 eligible articles are included . If publWe will evaluate all the strength of the body of evidence according to The Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline . The quaEsophageal cancer is a highly malignant cancer with a very poor prognosis. For resectable locally advanced esophageal cancer, neoadjuvant treatment could improve the prognosis of esophageal cancer. Effective neoadjuvant treatment options are needed, but current clinical treatment options are still limited for esophageal cancer. The application of immunotherapy is a potentially beneficial new neoadjuvant treatment option for esophageal cancer. To our best knowledge, this will be the first meta-analysis to evaluate the efficacy and safety of immunotherapy for the neoadjuvant treatment of esophageal cancer. The results of this study will provide a reliable basis for clinicians and patients to formulate the best pre-surgical treatment plan for resectable esophageal cancer.S1 Checklist(DOC)Click here for additional data file.


Antibiotic resistance is often reported and great concerned as one of public health problems especially people living with poverty in developing countries including Thailand. The hill tribe people is defined as vulnerable population for antibiotic resistance in Thailand due to poor economic and education status particularly the Lahu people who is the second greatest group of the hill tribe people in Thailand. The study aimed to estimate the prevalence, factors associated with, and typing major species of bacteria with antibiotic drugs resistance among the Lahu hill tribe people in northern Thailand.susceptibility was tested by Kirbey Bauer’s disc diffusion test. Chi-square and logistic regression were used to detect the associations between variables at the significant level of α = 0.05.A cross-sectional study was conducted to gather the information from the participants. A validated questionnaire was used for data collection. Participants who presented an illness related to infectious diseases were eligible to participate the study and were asked to obtain specific specimen; sputum, urine or stool. Antibiotic ; Escherichia coli (12.8%), and Enterobacter cloacae (8.0%). The prevalence of antibiotic resistance was 16.0%. Escherichia coli and Klebsiella pneumoniae species were found to have multidrug resistance that was greater than that of other species, while ampicillin was found to have the greatest drug resistance. It was found that those who had poor knowledge of antibiotic use had a 2.56-fold greater chance (95% CI = 1.09–5.32) of having antibiotic resistance than did those who had good knowledge of antibiotic use, and those who had poor antibiotic use behaviors had a 1.79-fold greater chance (95% CI = 1.06–4.80) of having antibiotic resistance than did those who had good antibiotic use behaviors.A total of 240 participants were recruited into the study. The majority had urinary tract infection (67.9%) with two major pathogenic species of the infectionEffective public health interventions are urgently needed to reduce antibiotic drug resistance among the Lahu people by improving their knowledge and skills regarding the proper use of antibiotics and eventually minimizing antibiotic resistance. Moreover, health care professionals should strictly follow the standard guideline to prescribe antibiotics. Antibiotic resistance is a recently emerging global threat to human health . Some anThe Ministry of Public Health in Thailand  reportedChiang Rai Province is located in northern Thailand and has long borders with neighboring countries such as Myanmar and Laos PDR. Many groups of hill tribe people live along the borders. Most hill tribe people have migrated from South China over many decades to settle in the remote and mountainous areas in northern Thailand. The hill tribe in Thailand has six main groups: Akah, Lahu, Homh, Yao, Karen, and Lisu . The LahThus, this study aimed to estimate the prevalence of and factors associated with major species of bacteria resisting antibiotics in the Lahu hill tribe people in northern Thailand.A cross-sectional study was applied to gather the information from the participants.The study settings were Lahu villages from Wiang Pa Pao District, Chiang Rai Province, Thailand. The study settings are located away from the center of Chiang Rai Province with 126 km.There were three selected villages for the study with total 1865 people living in villages. The villages are located in the rural area with seasoning poor transportation especially in the rainy season, then they are facing a difficulty in assessing health service. A large number of diarrheas were reported in these villages previous years through health promoting hospital system, so called Thailand Health Data Center System which is used in the whole country of Thailand for report the infectious diseases . The locThe health center is responsible for 14 villages with the total population at 9632 . There are 9 public health staffs; two nurses, two public health professional, 5 other health alien professionals. Three different antibiotics were available at health center; amoxicillin, roxithromycin, and dicloxacillin. Top five infection diseases reported from health center between January and December 2019 were 1) diarrhea, 2) pyrexia, 3) dengue fever, 4) conjunctivitis, and 5) hand, foot and mouth disease . Top thrThe Lahu people aged 15 years and over and living at three selected villages, and presenting at least one of signs or symptoms of an infection during the data collection date were the study population.The Lahu hill tribe people who had signs and symptoms of respiratory tract system, gastrointestinal tract system, or urinary tract infection during the data collection date were met the inclusion criteria of the study. The information on signs and symptoms relevant to the infection of these systems were also provided to village headmen to use it as preliminary criteria such as having fever, cough headach for respiratory tract infection between 1 week prior to the date of data collection. Having diarrhea was used as the major sing of gastrointestinal tract system, and dysuria, suprabic pain were used to identify the urinary tract infection one-week prior to the date of data collection. Those who had respiratory tract infection, they were asked to obtain suptum. Stool sample were asked for those who had an illness related to gastrointestinal tract system. While urine sample were asked from those who had an illness related to urinary tract infection. Those who could not provide essentail information regarding the study protocol were excluded from the study. All participants were asked to collect a suitable specimen  according to their illness presentation.n = Z2α/2P(1-P)/e2, where Z is the standard normal distribution at the confident 95%, then the Z = 1.96; P is the estimate true proportion which was estimated by the data from previous study, 23.0% [The standard formula sample size calculation for a cross-sectional study was used to estimate the sample size , n = Z2αy, 23.0% ; and theA questionnaire was developed from the literature review regarding the behaviors of antibiotic use and laboratory testing on antibiotic resistance. The questionnaire consisted of seven parts. In part one, 6 questions were used to collect sociodemographic characteristics, such as sex, age, highest education level, and marital status. In part two, 9 questions were used to collect data on the experiences of antibiotic use within the past 12 months, such as the source of antibiotic assessment, frequency, reason for taking antibiotics, and source of antibiotic knowledge. In part three, 10 questions were used to collect knowledge on infectious diseases. Those who scored 60.0% and over were defined as having good knowledge , 20. ThoThe quality of the questionnaire was validated by three steps. First, the content was validated by the item-objective congruence (IOC) method by five relevant experts: two medical doctors, an epidemiologist, a pharmacist, and a community nurse. The experts provided comments on the questions and a score. Questions that were scored less than 0.5 were excluded from the questionnaire set, those that were scored 0.5–0.7 were revised according to the comments, and questions that were scored greater than 0.7 were included in the questionnaire set. In the second step, a pilot was executed to detect the reliability and feasibility of the questionnaire among 15 samples who had characteristics similar to those of the study samples in Mae Suai District (district near Wiang Pa Pao District), Chiang Rai Province, Thailand. The overall reliability of parts three, four, and five were found to be 0.77, 0.78, and 0.78, respectively. In the last step, the questionnaire was revised and piloted again for 15 additional participants who had characteristics similar to those of the study samples.All participants were asked to collect suitable specimens according to their illness. Each individual was asked for one specimen. All specimens were transferred to the Men Rai Laboratory Center, Chiang Rai, Thailand, on the same day. The Kirbey-Bauer disc diffusion test, based on the Clinical and Laboratory Standards Institute (CLSI) Guidelines, was used to detect antibiotic resistance.Permission to access villages was granted by the district public health officer. Village headmen were contacted 3 days before having a small meeting. All information regarding the study was provided to the village headmen and village health volunteers. Before the date of data collection, all village members who met the eligible criteria were informed about the study protocols and invited to participate in the study. At the date of data collection, all participants were asked to obtain an informed consent form before data collection. For participants younger than 18 years old, informed consent forms were also obtained from their parents before data collection. The questionnaire was completed with the help of 15 village health volunteers (five persons in each village) who were fluent both the Thai and Lahu languages. They were trained for 6 hours on the content of the study, including a questionnaire, to clarify their understanding of and familiarize them with the full content of the questionnaire. The interviews lasted 25 min in each. Specimens were collected by licensed medical technicians from a hospital. Participants’ information such as name, ID number, specimen type and date of collection were labeled in individuals’ container. The sputum collection, participants were asked to collect their sputum by expectorating deep cough sputum directly into a sterile dry container. For urine collection, participants were asked to collect midstream urine with 10–20 mL in a clean and dry container. For the stool collection, participants were asked to collected 10–20 mL sample and put into a clean and dry container .All 240 participants were asked to collect specimens; 61 participants had sputum collected, 173 participants had urine collected, and 6 participants had stool collected. Specimens were kept and transferred for laboratory work at Chiang Rai city on the same day. Different specimens were placed on a specific plate before incubation at 35 °C for 24 h. Afterwards, the colonies were observed for the detection of pathogenic typing. Sensitivity to antibiotics was detected by the Kirbey-Bauer disc diffusion test to determine antibiotic resistance. The methods in laboratory were done under The Clinical and Laboratory Standards Institute (CLSI) Guidelines.The laboratory test was reported in three forms: susceptible (S), intermediate (I), and resistance (R).2 and Nagelkerke R2 before the results were interpreted.Data were double-entered into Excel spreadsheets and were checked for any errors before being transferred into SPSS version 24  for further analysis. Descriptive statistics were used to describe the participants’ characteristics in both categorical and continuous data. Chi-square tests and logistic regressions were used to identify the factors associated with antibiotic resistance among the participants at the significance level of α = 0.05. In the logistic regression steps, the Hosmer-Lemeshow chi-square test was used to assess the overall model prediction before and after the variables were included into the model. The fitness of the model was determined by the Cox-Snell RClassification of variables in the analysis, age was classified into two groups: < 60 years, ≥ 60 years. Antibiotic resistance was classified into two groups: resistance and non-resistance. Those who were susceptible and intermediate were classified as non-resistance, while resistance was classified as resistance in the analysis.A total of 240 participants participated the study; 70.4% were female, 25.4% were aged 30-40 years and 82.9% were married. More than half worked in the agricultural sector (55.4%) and had poor education, which was less than primary school (45.8%) Table .Table 1Urinary tract infectious diseases accounted for the largest group of infections in the past 12 months (67.9%), with 163 cases of urinary tract infection. A community health center (28.8%) was the favored location of healthcare services for the participants, followed by a district hospital (24.6%) and a drugstore (21.7%). The top three sources of antibiotic use were district hospitals (51.7%), drugstores (27.9%), and private medical clinics (22.5%).More than half of the participants received information about infectious diseases and antibiotics from health care professionals (Table Most of these sources showed good knowledge of infectious diseases (82.9%), while knowledge of and attitudes toward antibiotics and practices were poor  Table .Table 3p-value = 0.034). However, two other variables (age and antibiotic use behaviors) were found to have marginally significant differences between groups , Enterobacter cloacae (8.0%), Klebsiella pneumoniae (4.3%), Enterococcus faecalis (4.3%), and Staphylococcus coagulase negative (4.3%). The prevalence of antibiotic resistance was 16.0%. Klebsiella pneumoniae resisted ampicillin, cefazolin, cefoxitin, ciprofloxacin, levofloxacin and trimetroprim-sulfamethoxazole (TMP-SMX), while Escherichia coli demonstrated resistance to ampicillin, amoxicillin/clavulanic acid (amoxy-clav®), gentamycin, ciprofloxacin, levofloxacin and TMP-SMX. Ampicillin was found to have the highest resistance rate among the pathogenic bacteria, followed by cefoxitin, cefazolin, amoxy-clav®, and TMP-SMX (Table Of 240 specimens (participants), 187 samples were found to contain bacterial species, including normal flora. Fifty-five specimens were found to have more than 3 bacterial species, and only 30 samples were found to have drug resistance. The top-five bacterial species were detected in the specimens: MX Table .Table 5Two variables were found to be associated with antibiotic drug resistance among the Lahu people: knowledge and behaviors regarding antibiotic drug resistance. In the multivariate model, these two variables remained associated with antibiotic resistance, including knowledge and behaviors regarding antibiotic resistance. Those who had poor knowledge reading antibiotic use had a 2.56-fold greater chance (95% CI = 1.09–5.32) of having antibiotic resistance than did those who had good knowledge of antibiotic use. Those who had poor antibiotic use behaviors had a 1.79-fold greater chance (95% CI = 1.06–4.80) of having antibiotic resistance than did those who had good antibiotic use behaviors , Klebsiella pneumoniae (K. pneumoniae), Acinetobacter baumannii (A. baumannii), Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) [Escherichia coli strains were mostly present in infections and antibiotic resistance. In addition, a hospital-based study in Lebanon [Escherichia coli strains, were mostly susceptible to carbapenems and tigecycline, while Klebsiella species were mostly susceptible to amikacin and carbapenems. Moreover, a study in Hungary showed that the frequency of prescriptions from clinicians was related to the percentage of antibiotic resistance [E. coli were resistant to at least one antibiotic, with the highest resistance to amoxicillin [In our study, the prevalence of antibiotic resistance was 16.0%, and bacteria from urinary tract infections were the major cause of antibiotic resistance. A report from the Ministry of Public Health in Thailand said that the five most common bacterial species involved in antibiotic resistance were s (MRSA) . A studys (MRSA) . A commus (MRSA)  found th Lebanon  reportedsistance . In addixicillin . This reA study in Kenya  showed tA study on the epidemiology of antibiotic resistance in some selected communities in Thailand found that pathogeneses from upper respiratory tract and digestive tract infections were most common in antibiotic drug resistance . A systeIn our findings, we also found that knowledge and misuse antibiotic behaviors were associated with antibiotic resistance among the Lahu hill tribe people. This was supported by a study by Castro-Sánchez et al. , which rThe results from this study confirm that the problem of antibiotic resistance extends into the community, even in remote areas. It reflects a need for the design of an effective strategy at the nationwide level to address the problem, particularly among those who have poor economic and educational status. Moreover, improving access to health centers to obtain antibiotics while requiring their careful and proper use for the treatment of people living in remote areas is critical in Thailand.Some limitations were found during the study. First, some participant could not use Thai effectively, then we asked the village health volunteer who fluent both Thai and Lahu languages to help in completion the questionnaire and collecting specimen. However, some questions particularly in asking the questions about the urinary tract infection in females, the outcome might not be accurate and could impact the findings. Second, asking question on experience in use of antibiotics one year prior, it is one of our concerns during the study. Participants were asked and confirmed their response before responding to the questions. Third, knowing on the type of antibiotics, all antibiotic drugs available in village grocery and health center were shown to ensure that participants were able to identify the antibiotics. Last, generalization the findings to other populations would be limited due to the study participants were selected from three villages with high incident of the diseases.The Lahu people in Thailand are facing major challenges in their access to standard medical care due to the location of their village, which is far from the city and health center. They are also improperly using antibiotics, which had led them to have several bacterial infections that have eventually become resistant to antibiotics. Majority of the Lahu people receive antibiotics from the health care facility. Poor education and poor behaviors regarding the use of antibiotics are major factors influencing antibiotic resistance among the Lahu people. Public health interventions for improving knowledge and practices regarding the use of antibiotics should be urgently implemented. A regulation to prevent untrained health professionals from selling antibiotics, particularly in small groceries in villages, should be developed and implemented to reduce the improper use of antibiotics and minimize antibiotic resistance among the Lahu people in Thailand. Moreover, antibiotic prescription among health professionals should also be seriously followed the standard guideline. The surveillance of antibiotics resistance system should be immediately implemented and used as a major tool for monitoring antibiotics resistance in a whole country.


Self-Compacting Concrete (SCC) is a unique kind of concrete that tends to consolidate in terms of its weight. In this study, the prime target is to investigate the durability properties of SCC developed using eco-friendly economical waste binding materials as partial replacement to costly cement. This circular economy concept will not only help in the development of green concrete but will also help to improve the climatic condition by reducing the use and production of cement. An economical design methodology has been applied to produce environmentally friendly construction material. This research focuses on the application of Alum Sludge (AS) and Brick Dust (BD) in Self-Compacting Concrete (SCC). Both materials are waste materials containing binding properties. Performance of SCC developed using these two materials was tested considering mechanical properties of concrete using the destructive testing technique. Results showed that BD and AS can be utilized for up to 12% and 9% of replacement of cement, respectively, to achieve equal or higher compressive, tensile, and flexural strength. The application of BD and AS has demonstrated a subsequent improvement of SCC’s mechanical properties, i.e., compressive, tensile, and flexural strength. This study will help the production of composite green materials with the help of eco-friendly and economical waste materials for sustainable infrastructure development.  Self-Compacting Concrete (SCC) has a different behavior to that of normal concrete used around the globe in the construction industry. The effective self-consolidating capability of developed concrete without any external mechanical vibrations makes it much more powerful and useful in the construction industry. Its use of conveniently inexpensive and environment-friendly products is a great achievement. It is utilized in places where the vibration mechanism is not easy to install, and concrete composite material needs vibration to remove air bubbles to retain strength. It is also of great advantage to integrate and substitute many different waste products into the materials being used in the construction industry by increasing their partial replacement. Bricks are the major and most important type of utilized building material used around the globe and are a main part of this construction industry. With such large-scale production, there becomes a generated waste outcome in the form of brick dust or surkhi. In the conventional approach, prepared bricks are usually essentially masonry units made of simple inorganic or non-metallic materials that are fully sundried or burned in kilns to develop strength. Burnt bricks have a much stronger compressive strength property compared to sundried ones. Brick Dust (BD) is the waste dust material produced during burnt brick creation. It is used primarily as an effective substitute for concrete cement replacement. Thousands of tons of brick waste powder are generated every year around the globe, and it remains untreated and mishandled. BD mainly functions like sand as a filler, but it effectively imparts higher strength and invented hydraulic properties to self-compact concrete ,2. BD is2O3, which also a part of cement; therefore, it is an established fact that it also possesses binding properties and can be used as binder in construction process. Alum Sludge is the world’s most widely developed residual water treatment. Alum Sludge is essentially made up of colloidal alum hydroxides, usually used amorphous material. The current studies concentrate on the major impact of Alum Sludge powder as an active partial replacement of Portland cement and study the related mechanical properties of self-compacting concrete with high performance [w/c of 0.40. For the inclusion of Alum Sludge and Brick Dust in SCC, different proportions of substitution have been exercised. Selected percentages of the overall cement content used were 5, 10, 15, 20, 25, and 30%. Samples are cast to evaluate the compressive strengths and substitution effects on concrete mixes’ fresh properties. At 7, 14, and 21 days of age, specimens are cured and screened for both hardened and fresh properties. Alum Sludge (AS) is essentially a by-product produced worldwide that is derived from water treatment units and plants that use aluminum salts as primary coagulants. It has chemical composition of Alformance . Sieve aIn the trend to use industrial waste and by-products as an effective useful substitution of ingredients utilized in the construction industry, rapid growth is observed. This approach gives an effective and environmentally sustainable superiority to erection development around the globe ,6,7.Waste is becoming a serious public health hazard around the world. On the other hand, recognizing and utilizing it as viable raw material sourcing for the construction industry would improve resource efficiency because implementing such an approach could result in the development of a Circular Economy (CE) system that closes the material loops. As a result, natural resource removal is minimized, the carbon footprint is reduced, and waste is eliminated ,10,11,12Green material has often been considered an important aspect in enhancing the aspects of sustainability: ecological, economical, and social . This wiBD is created when bricks and brick kilns are loaded or unloaded where they are burned. Since ancient times, pozzolanic materials such as brick dust and other powder ceramics have been used in concrete. Bricks are generally made of large Clay materials consisting of about 20–30% Alumina, about 50–60% Silica, and various other oxides and carbonates. Clay is truly responsible for Surkhi’s most successful pozzolanic behavior. Tile used to produce bricks does not have a substantial pozzolanic property in scope, but it develops a visible pozzolanic quality when it is fired with other agents such as lime during the brick manufacturing process ,17,18,193) and water are formed as a result. The most important chemical reactions are as follows:Brick Dust or Surkhi behaves as pozzolana and responds as an outcome with the lime in an active water presence. If carbon dioxide reacts effectively with calcium hydroxide in the process, calcium carbonate  is “Superplasticizer” because it is also an essential part of SCC concrete. Superplasticizers are utilized to form workable concrete in circumstances where the placing of concrete is unapproachable or in circumstances where fast employment is vital . By incoThese superplasticizers are condensates of sulfonated melamine formaldehyde or formaldehyde condensates of sulfonated naphthalene . The plaThe Standard Portland Cement of the Grade 53 has been used. The cement was truly clean, new, and free of lumps and unwanted impurities.The fine aggregate of the Lawrencepur type was used to develop the sample. It was passed through sieve #4 carefully. The effective fineness module of the used fine aggregate has been defined by ASTM C 136-93 ,30,31,32Coarse aggregates are a significant part of concrete and are used in the current District Abbottabad “Margalla” crush studies. Coarse aggregates are analyzed following the ASTM C 136 standard through sieve testing.Self-compacting concrete is a useful mix prepared in ordinary traditional concrete by induction of a superplasticizer. SCC has been created out of social necessity, like many innovative products. To test and create the most effective and beneficial combination, various ratios are chosen. The amount of plasticizer varies from 2–3% depending upon the intensity of workability and slump. Just applying the plasticizer after adding water to the mix improves the attributes of decent workability, and the simple positioning for SCC is equipped close to ordinary concrete. It performs the J-circle, V-funnel, fresh mix, and slump tests. To prepare the SCC, a standard mechanical mixer is used. Because of its high mobility, it is much easier to handle and place than standard concrete ,29. In tw/c. The following is the mix design modified by Alum Sludge (AS) and Brick Dust (BD) for the prepared SCC samples.Various experiments were carried out to analyze the mechanical foundation as well as the fresh properties of Alum Sludge and Brick Dust modified SCC concrete. Self-compacting concrete mixes of varying AS and BD percentages are prepared with 0, 3, 6, 9, 12, and 15% substitution of ordinary Portland cement. The blend used was the 1:1.5:3 mixing ratio of the M20 concrete and a 0.40 Standard SCC fresh property tests were performed, including the standard V-funnel tests, L-Box, and J-ring tests, to explore the fresh properties of SCC concrete ,33,34,35J-Ring Test: The basic generic J-Ring test was used for the thorough assessment of concrete flow capability for the detailed evaluation of the key fresh assets of updated SCC. The standard J-Ring system available in the laboratory of the institute was used efficiently to perform the test according to the BS requirements shown in V-Funnel Test: The generic V-funnel testing tool was employed to perform this experiment efficiently as shown in L-Box Test: One of the most important and useful SCC tests is the “L-box test,” which was applied effectively to review and calculate the passing competence of the full filling and concrete. This test is accurate and applicable to the required concrete character of high flow capability, as shown in The detailed evaluation of the fresh properties of the prepared SCC mixes with Alum Sludge and Brick Dust are shown in The results indicated in The primary characteristics that are considered for judging the quality, strength, and degradation of concrete are its mechanical properties  . They alStrength testing of concrete materials is identified with substantial burden strength testing. Two kinds of specimens were delivered to quantify substantial strength: block (600 × 600 × 600) and chamber (600 × 1200). Likewise, the Indirect Tension test, otherwise called the Brazilian and Japanese test, is done to gauge the upward impact of the compressive burden on the vertically stacked chamber to test its rigidity. A compressed wood strip is mounted at the mark of utilization to lessen the higher effect of tension on the substantial surface. The flexural examination is done on a shaft substantial example. There ought to be, for the most part, some substantial obstruction before breaking begins, and the heap is moved to reinforcing. The get-together displayed in Samples were checked for compressive strength determination, as shown in One of the most important features of tensile strength is that concrete is highly vulnerable to cracking. The standard cylinder specimen is laid between the compression machine plates, and then the behavior of the specimen is noted along the perpendicular diameter. Three specimens were developed and tested for each ratio (five ratios) and substance , as shown in The testing results of split tensile strength are shown in The action of BD has been found to be better when compared to its other competitor alum sludge with the percentage increase. The virtual analysis illustrates that concrete strength can be tested, as shown in Flexural strength is one measure of concrete’s tensile strength. To test flexural strength, a concrete beam’s resistance to loading is assessed. Three specimens were developed and tested for each ratio (five ratios) and substance . These beams were subjected to a charging system of three stages. It is important to see the comparable flexural strength in Graphical representation of flexural strength results is shown in The testing results of mechanical properties such as compressive strength, split tensile strength, and flexural strength are shown in The testing results of compressive strength shown in The testing results of split tensile strength are shown in The findings of flexural strength are presented in the bar charts of The results concluded that with the increase of AS replacement percentage, both the compressive and split tensile strengths increased, but only up to a certain limit of 9% addition. After that, with increased ratios, the effective compressive strengths decreased due to the increased AS content and low cement content that caused lesser hydration reactions and failed to form the binding jell to hold aggregates in strength ,40. BricApplication of the developed SSC using BD and AS can be helpful as an economical solution and effective utilization of waste materials for construction. This combination of materials will serve as a low-cost solution to the construction industry and follows the principles of sustainable development goals.In the current research conducted upon the Alum Sludge and Brick Dust that were incorporated in SCC by an effective partial replacement of the ordinary Portland cement, we came can develop the following comprehensive conclusions based on the results obtained after deep evaluation by testing.The maximum workability trend was noted to be at 15% replacement of cement with Brick Dust and Alum Sludge, and after that, it decreased.The compressive strength pattern for the addition of BD in SCC tends to elevate by increasing the content until 12%. Beyond this point, the replacement increase affected the compressive strengths.The split tensile strengths of SCC samples increased by increasing the content of BD up to the addition of 12%, while after this, it effectively tends to decrease the associated enhancements.Alum Sludge (AS) is a useful by-product that comes out as a waste from the water treatment plants. The workability behavior of AS modified SCC remained normal to the generally observed trend, and it increases slightly with increased percentages.The concrete with 9% AS shows a significantly improved strength gain across all curing ages.With the utilization of both waste materials, concrete development can take a step forward to achieving a sustainable yet low-cost and durable construction trend in our construction industry.The proposed modification of binding material with AS and BD can not only help in the development of concrete, but can also be used in mortar formation, and at some stage, with the help of chemical scientists, a modified low-cost cement can be developed, which can not only help in low cost-economical material composite formation but will also reduce the construction cost. In the future, this combination can also help in the development of different types of composite materials for large infrastructure projects like dams. This will help in the reduction of construction costs.


More than 90% of antibiotics are prescribed in primary care, but 50% may be unnecessary. Reducing unnecessary antibiotic overuse is needed to limit antimicrobial resistance. We conducted a pragmatic trial of a primary care provider-focused antimicrobial stewardship intervention to reduce antibiotic prescriptions in primary care.Primary care practitioners from six primary care clinics in Toronto, Ontario were assigned to intervention or control groups to evaluate the effectiveness of a multi-faceted intervention for reducing antibiotic prescriptions to adults with respiratory and urinary tract infections. The intervention included provider education, clinical decision aids, and audit and feedback of antibiotic prescribing. The primary outcome was total antibiotic prescriptions for these infections. Secondary outcomes were delayed prescriptions, prescriptions longer than 7 days, recommended antibiotic use, and outcomes for individual infections. Generalized estimating equations were used to estimate treatment effects, adjusting for clustering by clinic and baseline differences.There were 1682 encounters involving 54 primary care providers from January until May 31, 2019. In intervention clinics, the odds of any antibiotic prescription was reduced 22% (adjusted Odds Ratio (OR) = 0.78; 95% Confidence Interval (CI) = 0.64.0.96). The odds that a delay in filling a prescription was recommended was increased , while prescription durations greater than 7 days were reduced . Recommended antibiotic use was similar in control (85.4%) and intervention clinics .A community-based, primary care provider-focused antimicrobial stewardship intervention was associated with a reduced likelihood of antibiotic prescriptions for respiratory and urinary infections, an increase in delayed prescriptions, and reduced prescription durations.NCT03517215).clinicaltrials.gov (The online version contains supplementary material available at 10.1186/s12875-021-01536-3. The need to more appropriately use antibiotics in order to limit antibiotic resistance has been widely endorsed , 2. HoweCommunity-based AMS programs have been tested in Scotland , Spain , the UniOne factor may be the clinical uncertainty community providers report in trying to distinguish viral from bacterial infections, owing to their similar clinical presentations . There ast 2019 until May 31st 2019. Baseline prescribing rates for each clinic were calculated from prescribing data for the previous winter. Ethics approval was obtained from research ethics boards of the University of Toronto, Mount Sinai Hospital, Women’s College Hospital and North York General Hospital. The study was registered with clinicaltrials.gov on 08/05/2018 (registration number NCT03517215).The University of Toronto Practice-based Research Network (UTOPIAN) consists of 14 family medicine clinics in south central Ontario affiliated with the Department of Family and Community Medicine of the University of Toronto. Two clinics had participated in a pilot study of the intervention and were excluded . Of the Randomization by minimization was conducted due to the small number of clinics . Using pThe intervention was a multi-faceted program of clinician education, clinical decision aids for prescribing decisions, patient information leaflets, audit and feedback of clinic prescription practices, local clinic support, and incentives. An initial one hour on-site education session was delivered by study staff at each clinic regarding antimicrobial resistance, stewardship, and interventions for reducing antibiotic prescribing. The clinic’s prescribing practices the previous winter were reviewed, and providers set prescribing goals. Providers were then sent electronic modules to complete over four months explaining the use of the decision aids for a given condition and optimal prescription practices. Additional on-site sessions were held during the winter to review antibiotic utilization and revise prescribing goals.The modules addressed five infections: acute sinusitis, acute uncomplicated upper respiratory infections (URI), sore throat presentations , acute bronchitis and acute uncomplicated cystitis. These conditions account for approximately 50% of community antibiotic prescriptions in Canada . ModulesModule topics included prescribing issues for each infection and a 1-page clinical prescribing decision aid. The aid addressed criteria for diagnosis, indications for antibiotics, recommended first line antibiotic choices, treatment durations, and ‘red flags’ for serious presentations. Validated clinical decision rules were incorporated into prescribing aides where available , 20. ModClinicians at intervention sites received $200 compensation, pro-rated for the number of completed modules and education sessions. Continuing medical education credits and a free antibiotic prescribing formulary  were alsst 2018 and February 28th 2018 (baseline period) or between January 1st 2019 and May 31st 2019 , and with an eligible ICD-9 diagnosis code  identified from billing records. Urinary infections involving males or pregnant females were excluded, as were follow-up visits of previously treated infections.Data from eligible visit encounters were abstracted from electronic medical record (EMR) systems at each clinic. Eligible visits were defined as those involving adults 18 years of age or older, seen by a consenting physician between January 1To identify most eligible visits, a number of ICD-9 billing codes were selected. These included 460 (URI), 462 (pharyngitis), 463 (tonsillitis), 461(acute sinusitis), 466 (acute bronchitis), and (595) acute uncomplicated cystitis. In addition, visits coded 464 (laryngitis), 599 , 486 (pneumonia), and 487(influenza) were included to ensure other respiratory and urinary symptom visits had not been mislabeled. This was assessed by comparing a provider’s written diagnosis and the billing code. Two independent raters reviewed all visits using standardized coding rules developed for the study (Available upon request). The final visit diagnosis was adjusted if the written diagnosis indicated an eligible infection presentation. Non-infection diagnoses (e.g.’new patient visit’) and non-eligible infections  were excluded, as were presentations involving asthma or chronic lung disease. Raters agreed on the final diagnosis for 94% of visits. Disagreements were resolved through case review and agreement by both raters.Data abstracted from each visit included patient age, sex, antibiotic allergies, clinic site, visit date, clinician type, billing ICD-9 code, clinician written diagnosis, selected vital signs, tests ordered, and antibiotic prescriptions. Prescription information included the antibiotic name, prescription duration, and if a patient was advised to delay filling the prescription (‘delayed prescription’).The primary study outcome was total antibiotic prescriptions for the five selected conditions combined  in each arm. Secondary outcomes were the proportion of prescriptions issued as delayed antibiotic prescriptions, prescriptions for longer than 7 days duration, and total, delayed and long duration prescriptions for each infection individually. A post-hoc decision was made to also assess test utilization.A 25% relative reduction in the total prescriptions was selected as the minimum important effect size, consistent with previously reported national goals , a samplThere were 1,904 eligible visits from January 1, 2019 until May 31, 2019. After exclusions, 1682 (88.3%) visits were available for analysis; 943(56.1%) in control clinics and 739 (43.9%) from intervention clinics  than in control clinics . The odds that intervention physicians advised patients to start antibiotics immediately were reduced 37% compared to control clinics . Antibiotic prescriptions for longer than 7 days duration were also decreased at interventions clinic (21.3%) compared to control clinics . Use of recommended antibiotics were high in both control (84.9%) and intervention (92.2%) clinics (adjusted p=0.37).There were no reductions in total antibiotic prescriptions for individual infections Table . PrescriA post-hoc analysis of the effect of testing recommendations included in clinical decision aids found a throat swab or rapid strep test was ordered more frequently at intervention clinics  than control clinics  for sore throat presentations . Chest x-rays were ordered more often at intervention clinics  than control clinics  for cases of acute bronchitis . Urinalysis and urine culture utilization was similar in both control (93.3%) and intervention (90.7%) clinics.This community-based, primary care provider-focused antimicrobial stewardship intervention reduced total antibiotic prescriptions to adults with a respiratory or urinary tract infection, increased the proportion issued as delayed prescriptions, and reduced prescription durations for longer than 7 days.Although the observed crude rates of total antibiotic prescriptions were not different between intervention and control clinics, there were a number of differences in baseline characteristics between the two groups of clinics that persisted after randomization. When clinic difference were adjusted for, there was a 22% reduction in the odds of prescribing an antibiotic at intervention clinics. In addition, these prescriptions were twice as likely to be issued as delayed prescriptions. This is relevant as only 33% of prescriptions with instructions to delay starting may ultimately be filled . As a reOther multi-faceted ASP intervention studies have varied in the intervention focus, types of infections, and measures of antibiotic use , 30, 31.Providers were compensated for participating in the current study. An American study similarly provided compensation to participants with a 70% participation rate . IncentiA limitation of the study was not all clinicians at each clinic participated. Participating clinicians may have been more receptive to the AMS intervention than might be seen in the broader primary care community. Another limitation was the short study duration over one winter season. Whether the impact on prescriptions would be sustained is unclear. AMS effects have declined when interventions are removed , 37. TheThis study has demonstrated that clinically important changes in antibiotic utilization in primary care clinics are possible with local stewardship efforts involving provider-focused education, clinical decision aids, clinic support, ongoing audit and feedback, and compensation for ASP activities. Structured and supported community-based antimicrobial stewardship efforts, similar to those in hospital settings, warrant further study.Additional file 1: Supplementary Table 1. Associations between visit, patient, and condition characteristics, and having received an antibiotic prescription.


In children, urinary tract infection (UTI) represents one of the most common indications for antibiotics. While previous data has demonstrated high rates of misdiagnosis and inconsistencies with empiric antibiotics, the impact and opportunities for antibiotic reduction once final culture and susceptibility data are available, particularly in pediatric patients seen in the emergency department (ED), is unknown.This was a retrospective study conducted over a period of 18-months, which included subjects less than 18 years of age who were discharged from the ED with a diagnosis of UTI. Episodes in which urine cultures were negative or grew only mixed urogenital flora were considered possible for discontinuation. De-escalation was considered possible in episodes in which identified bacteria were susceptible to more narrow spectrum agents than the prescribed empiric antibiotic. Rates of discontinuation and de-escalation were calculated as proportions, and excess days of therapy were described. Subjects whose empiric antibiotics were active against isolated bacteria were compared to those with bacteria resistant to empiric therapy.Escherichia coli (84%). Empiric antibiotic therapy and duration varied and were active against isolated bacteria in 39 (76%) of the episodes. Subjects whose antibiotics were inactive were more likely to be Hispanic and receive cephalexin [Table 3]. Antibiotics were discontinued in 3 of the 27 possible episodes (11%), resulting in 127 extra antibiotic days, median of 6 (IQR=10 days) days per episode. In 20 episodes there was an opportunity for de-escalation, but it was never attempted, leading to 131 extra days of broad-spectrum antibiotics .A total of 87 episodes of UTI were identified. Pathogenic bacteria were isolated in 51 (59%) of the 78 episodes in which urine cultures were sent, most commonly Table 1. Microbiology and resistance profile of bacteria isolated from urine culturesTable 2. Empiric antibiotic regimens, including type of antibiotic and durationTable 3. Comparison of episodes in which empiric antibiotics were active against isolated bacteria versus those in which empiric antibiotics were inactiveAntibiotics are rarely adjusted after discharge from the ED. Lack of adjustment results in unnecessary total and broad-spectrum antibiotic exposures. Initiatives designed to improve antibiotic use post-discharge could result in significant decreases in unnecessary antibiotics, and ultimately reduced rates of antibiotic resistance.All Authors: No reported disclosures