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      Blood culture utilization and epidemiology of antimicrobial-resistant bloodstream infections before and during the COVID-19 pandemic in the Indonesian national referral hospital

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          Abstract

          Background

          There is a paucity of data regarding blood culture utilization and antimicrobial-resistant (AMR) infections in low and middle-income countries (LMICs). In addition, there has been a concern for increasing AMR infections among COVID-19 cases in LMICs. Here, we investigated epidemiology of AMR bloodstream infections (BSI) before and during the COVID-19 pandemic in the Indonesian national referral hospital.

          Methods

          We evaluated blood culture utilization rate, and proportion and incidence rate of AMR-BSI caused by WHO-defined priority bacteria using routine hospital databases from 2019 to 2020. A patient was classified as a COVID-19 case if their SARS-CoV-2 RT-PCR result was positive. The proportion of resistance was defined as the ratio of the number of patients having a positive blood culture for a WHO global priority resistant pathogen per the total number of patients having a positive blood culture for the given pathogen. Poisson regression models were used to assess changes in rate over time.

          Results

          Of 60,228 in-hospital patients, 8,175 had at least one blood culture taken (total 17,819 blood cultures), giving a blood culture utilization rate of 30.6 per 1,000 patient-days. A total of 1,311 patients were COVID-19 cases. Blood culture utilization rate had been increasing before and during the COVID-19 pandemic (both p < 0.001), and was higher among COVID-19 cases than non-COVID-19 cases (43.5 vs. 30.2 per 1,000 patient-days, p < 0.001). The most common pathogens identified were K. pneumoniae (23.3%), Acinetobacter spp. (13.9%) and E. coli (13.1%). The proportion of resistance for each bacterial pathogen was similar between COVID-19 and non-COVID-19 cases (all p > 0.10). Incidence rate of hospital-origin AMR-BSI increased from 130.1 cases per 100,000 patient-days in 2019 to 165.5 in 2020 (incidence rate ratio 1.016 per month, 95%CI:1.016–1.017, p < 0.001), and was not associated with COVID-19 ( p = 0.96).

          Conclusions

          In our setting, AMR-BSI incidence and etiology were similar between COVID-19 and non-COVID-19 cases. Incidence rates of hospital-origin AMR-BSI increased in 2020, which was likely due to increased blood culture utilization. We recommend increasing blood culture utilization and generating AMR surveillance reports in LMICs to inform local health care providers and policy makers.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13756-022-01114-x.

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          Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis

          (2022)
          Summary Background Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen–drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen–drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level. Findings On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62–6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911–1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9–35·3), and lowest in Australasia, at 6·5 deaths (4·3–9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000–1 270 000) deaths attributable to AMR and 3·57 million (2·62–4·78) deaths associated with AMR in 2019. One pathogen–drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000–100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae. Interpretation To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen–drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.
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            Surviving Sepsis Campaign : International Guidelines for Management of Sepsis and Septic Shock 2021

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              Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis

              Objective The proportion of patients infected with SARS-CoV-2 that are prescribed antibiotics is uncertain, and may contribute to patient harm and global antibiotic resistance. Our objective was to estimate the prevalence and associated factors of antibiotic use in patients with confirmed COVID-19. Methods We searched MEDLINE, OVID Epub and EMBASE for published literature on human subjects in English up to June 9, 2020. Inclusion criteria were any healthcare settings and age groups; randomized controlled trials; cohort studies; case series with >10 patients; experimental or observational design that evaluated antibiotic prescribing. The main outcome of interest was proportion of COVID-19 patients prescribed an antibiotic, stratified by geographical region, severity of illness, and age. We pooled proportion data using random effects meta-analysis. Results We screened 7469 studies, from which 154 were included in the final analysis. Antibiotic data were available from 30,623 patients. The prevalence of antibiotic prescribing was 74.6% (95% CI 68.3 to 80.0%). On univariable meta-regression, antibiotic prescribing was lower in children (prescribing prevalence odds ratio (OR) 0.10, 95%CI 0.03 to 0.33) compared to adults. Antibiotic prescribing was higher with increasing patient age (OR 1.45 per 10 year increase, 95%CI 1.18 to 1.77) and higher with increasing proportion of patients requiring mechanical ventilation (OR 1.33 per 10% increase, 95%CI 1.15 to 1.54). Estimated bacterial co-infection was 8.6% (95% CI 4.7-15.2%) from 31 studies. Conclusions Three-quarters of patients with COVID-19 receive antibiotics, prescribing is significantly higher than the estimated prevalence of bacterial co-infection. Unnecessary antibiotic use is likely high in patients with COVID-19. Registration PROSPERO (ID CRD42020192286).
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                Author and article information

                Contributors
                robert.sinto01@ui.ac.id , robert.sinto@ndm.ox.ac.uk
                chen_tropik@hotmail.com
                s_setiati@yahoo.com
                suhendro.dr@gmail.com
                ejnelwan@yahoo.com
                deanhandimulya@gmail.com
                karyanti@ikafkui.net
                ariprayitno@yahoo.com
                sumariyono0704@gmail.com
                camoore@sgul.ac.uk
                raph.hamers@ndm.ox.ac.uk
                nickd@tropmedres.ac
                direk@tropmedres.ac
                Journal
                Antimicrob Resist Infect Control
                Antimicrob Resist Infect Control
                Antimicrobial Resistance and Infection Control
                BioMed Central (London )
                2047-2994
                19 May 2022
                19 May 2022
                2022
                : 11
                : 73
                Affiliations
                [1 ]GRID grid.9581.5, ISNI 0000000120191471, Division of Tropical and Infectious Diseases, Department of Internal Medicine, , Cipto Mangunkusumo National Hospital - Faculty of Medicine Universitas Indonesia, ; Jakarta Pusat, DKI Jakarta, 10430 Indonesia
                [2 ]GRID grid.9581.5, ISNI 0000000120191471, Faculty of Medicine Universitas Indonesia, ; Jakarta Pusat, DKI Jakarta, 10440 Indonesia
                [3 ]GRID grid.487294.4, Infection and Antimicrobial Resistance Control Committee, , Cipto Mangunkusumo National Hospital, ; Jakarta Pusat, DKI Jakarta, 10430 Indonesia
                [4 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, , University of Oxford, ; Oxford, OX3 7LG UK
                [5 ]GRID grid.487294.4, Department of Internal Medicine, , Cipto Mangunkusumo National Hospital, ; Jakarta Pusat, DKI Jakarta, 10430 Indonesia
                [6 ]GRID grid.487294.4, Faculty of Medicine Universitas Indonesia, Center for Clinical Epidemiology and Evidence Based Medicine, , Cipto Mangunkusumo National Hospital, ; Jakarta Pusat, DKI Jakarta, 10430 Indonesia
                [7 ]GRID grid.487294.4, Department of Clinical Pathology, , Cipto Mangunkusumo National Hospital, ; Jakarta Pusat, DKI Jakarta, 10430 Indonesia
                [8 ]GRID grid.487294.4, Department of Child Health, , Cipto Mangunkusumo National Hospital, ; Jakarta Pusat, DKI Jakarta, 10430 Indonesia
                [9 ]GRID grid.487294.4, Director of Medical Service and Nursing, Board of Directors, , Cipto Mangunkusumo National Hospital, ; Jakarta Pusat, DKI Jakarta, 10430 Indonesia
                [10 ]GRID grid.264200.2, ISNI 0000 0000 8546 682X, Centre for Neonatal and Paediatric Infection, , St George’s, University of London, ; Cranmer Terrace, London, SW17 0RE UK
                [11 ]GRID grid.418754.b, ISNI 0000 0004 1795 0993, Eijkman-Oxford Clinical Research Unit, ; Jakarta Pusat, DKI Jakarta, 10430 Indonesia
                [12 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, , Mahidol University, ; Bangkok, 10400 Thailand
                [13 ]GRID grid.10223.32, ISNI 0000 0004 1937 0490, Department of Tropical Hygiene, Faculty of Tropical Medicine, , Mahidol University, ; Bangkok, 10400 Thailand
                Author information
                https://orcid.org/0000-0003-3857-300X
                https://orcid.org/0000-0002-9572-5260
                Article
                1114
                10.1186/s13756-022-01114-x
                9117993
                35590391
                efa56243-ef86-40e9-ae61-b5766f4f8ba6
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 26 March 2022
                : 11 May 2022
                Funding
                Funded by: Beasiswa Pendidikan Indonesia - the Ministry of Education, Culture, Research, and Technology Republic of Indonesia; and Indonesian Endowment Fund for Education
                Award ID: 202101182688
                Funded by: FundRef http://dx.doi.org/10.13039/100010269, Wellcome Trust;
                Award ID: 220211
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Infectious disease & Microbiology
                antimicrobial resistance,blood culture,blood culture utilization,bloodstream infection,covid-19,indonesia

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