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      Epidemiology and burden of multidrug-resistant bacterial infection in a developing country

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          Abstract

          Little is known about the excess mortality caused by multidrug-resistant (MDR) bacterial infection in low- and middle-income countries (LMICs). We retrospectively obtained microbiology laboratory and hospital databases of nine public hospitals in northeast Thailand from 2004 to 2010, and linked these with the national death registry to obtain the 30-day mortality outcome. The 30-day mortality in those with MDR community-acquired bacteraemia, healthcare-associated bacteraemia, and hospital-acquired bacteraemia were 35% (549/1555), 49% (247/500), and 53% (640/1198), respectively. We estimate that 19,122 of 45,209 (43%) deaths in patients with hospital-acquired infection due to MDR bacteria in Thailand in 2010 represented excess mortality caused by MDR. We demonstrate that national statistics on the epidemiology and burden of MDR in LMICs could be improved by integrating information from readily available databases. The prevalence and mortality attributable to MDR in Thailand are high. This is likely to reflect the situation in other LMICs.

          DOI: http://dx.doi.org/10.7554/eLife.18082.001

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          Antimicrobial resistance is a global problem. Each year, an estimated 23,000 deaths in the United States and 25,000 deaths in the European Union are extra deaths caused by bacteria resistant to antibiotics. People in low- and middle-income countries are also using more antibiotics, in part because of rising incomes, lower costs of antibiotics, and a lack of control of antimicrobial usage in the hospitals and over-the-counter sales of the drugs. These factors are thought to be driving the development and spread of bacteria that are resistant to multiple antibiotics in countries such as China, India, Indonesia and Thailand. However, a lack of information makes it difficult to estimate the size of the problem and, then, to track how antimicrobial resistance and multi-drug resistance is changing over time in these and other low- and middle-income countries.

          Now, by integrating routinely collected data from a range of databases, Lim, Takahashi et al. estimate that around an extra 19,000 deaths are caused by multi-drug resistant bacteria in Thailand each year. Thailand has a population of about 70 million, and so, per capita, this estimate is about 3 to 5 times larger than those for the United States and European Union (which have a populations of about 300 million and 500 million, respectively). Lim, Takahashi et al. also show that more of the bacteria collected from patients are resistant to multiple antimicrobial drugs and that the burden of antimicrobial resistance in Thailand is worsening over time.

          These findings suggest that more studies with a systematic approach need to be done in other low- and middle-income countries, especially in countries where microbiological laboratories are readily available and routinely used. Further work is also needed to identify where resources and attentions are most needed to effectively fight against antimicrobial resistance in low- and middle-income countries.

          DOI: http://dx.doi.org/10.7554/eLife.18082.002

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          Most cited references22

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          Antibiotic resistance-the need for global solutions.

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

            Organisms resistant to antimicrobials continue to emerge and spread. This study was performed to measure the medical and societal cost attributable to antimicrobial-resistant infection (ARI). A sample of high-risk hospitalized adult patients was selected. Measurements included ARI, total cost, duration of stay, comorbidities, acute pathophysiology, Acute Physiology and Chronic Health Evaluation III score, intensive care unit stay, surgery, health care-acquired infection, and mortality. Hospital services used and outcomes were abstracted from electronic and written medical records. Medical costs were measured from the hospital perspective. A sensitivity analysis including 3 study designs was conducted. Regression was used to adjust for potential confounding in the random sample and in the sample expanded with additional patients with ARI. Propensity scores were used to select matched control subjects for each patient with ARI for a comparison of mean cost for patients with and without ARI. In a sample of 1391 patients, 188 (13.5%) had ARI. The medical costs attributable to ARI ranged from $18,588 to $29,069 per patient in the sensitivity analysis. Excess duration of hospital stay was 6.4-12.7 days, and attributable mortality was 6.5%. The societal costs were $10.7-$15.0 million. Using the lowest estimates from the sensitivity analysis resulted in a total cost of $13.35 million in 2008 dollars in this patient cohort. The attributable medical and societal costs of ARI are considerable. Data from this analysis could form the basis for a more comprehensive evaluation of the cost of resistance and the potential economic benefits of prevention programs.
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              A review of adjusted estimators of attributable risk.

              J Benichou (2001)
              This paper reviews adjusted methods of estimation of attributable risk (AR), that is methods that allow one to obtain estimates of AR while controlling for other factors. Estimability and basic principles of AR estimation are first considered and the rationale for adjusted AR estimators is discussed. Then, adjusted AR estimators are reviewed focusing on cross-sectional, cohort and case-control studies. Two inconsistent adjusted estimators are briefly commented upon. Next, adjusted estimators based on stratification, namely the weighted-sum and Mantel-Haenszel (MH) approaches, are reviewed and contrasted. It appears that the weighted-sum approach, which allows for full interaction between exposure and adjustment factors, can be affected by small-sample bias. By contrast, the MH approach, which rests on the assumption of no interaction between exposure and adjustment factors may be misleading if interaction between exposure and adjustment factors is present. Model-based adjusted estimators represent a more general and flexible approach that includes both stratification approaches as special cases and offers intermediate options. Bruzzi et al.'s and Greenland and Drescher's estimators are reviewed and contrasted. Finally, special problems of adjusted estimation are considered, namely estimation from case-cohort data, estimation for risk factors with multiple levels, for multiple risk factors, for recurrent events, estimation of the prevented and preventable fractions, and estimation of the generalized impact fraction. Comments on future directions are presented.
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                Author and article information

                Contributors
                Role: Reviewing editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                06 September 2016
                2016
                : 5
                : e18082
                Affiliations
                [1 ]deptMahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine , Mahidol University , Bangkok, Thailand
                [2 ]deptFaculty of Medicine Siriraj Hospital , Mahidol University , Bangkok, Thailand
                [3 ]deptBureau of Epidemiology, Department of Disease Control , Ministry of Public Health , Nonthaburi, Thailand
                [4 ]deptCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine , University of Oxford , Oxford, United Kingdom
                [5 ]London School of Hygiene and Tropical Medicine , London, United Kingdom
                [6 ]University of Cambridge, Addenbrooke’s Hospital , Cambridge, United Kingdom
                [7 ]deptDepartment of Tropical Hygiene, Faculty of Tropical Medicine , Mahidol University , Bangkok, Thailand
                [8]University of KwaZulu Natal , South Africa
                [9]University of KwaZulu Natal , South Africa
                Author notes
                [†]

                These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0003-2555-6980
                http://orcid.org/0000-0003-2309-1171
                http://orcid.org/0000-0002-1718-2782
                http://orcid.org/0000-0001-7240-5320
                Article
                18082
                10.7554/eLife.18082
                5030096
                27599374
                9f8cf369-7996-4d36-9f0d-05968a486838
                © 2016, Lim et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 23 May 2016
                : 24 August 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004397, Ministry of Public Health;
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 100484/Z/12/Z
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 101103/Z/13/Z
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Epidemiology and Global Health
                Research Article
                Custom metadata
                2.5
                The burden of antimicrobial resistance in Thailand is deteriorating over time, and 19,122 deaths in the country in 2010 were excess deaths caused by multidrug-resistant bacterial infection.

                Life sciences
                antimicrobial resistant,staphylococcus aureus,k. pneumoniae,p. aeruginosa,enterococcus,acinetobacter,e. coli,other

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