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      Economic burden of antibiotic resistance in ESKAPE organisms: a systematic review


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          Antibiotic resistance (ABR) is one of the biggest threats to global health. Infections by ESKAPE ( Enterococcus, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and E. coli) organisms are the leading cause of healthcare-acquired infections worldwide. ABR in ESKAPE organisms is usually associated with significant higher morbidity, mortality, as well as economic burden. Directing attention towards the ESKAPE organisms can help us to better combat the wide challenge of ABR, especially multi-drug resistance (MDR).


          This study aims to systematically review and evaluate the evidence of the economic consequences of ABR or MDR ESKAPE organisms compared with susceptible cases or control patients without infection/colonization in order to determine the impact of ABR on economic burden.


          Both English-language databases and Chinese-language databases up to 16 January, 2019 were searched to identify relevant studies assessing the economic burden of ABR. Studies reported hospital costs (charges) or antibiotic cost during the entire hospitalization and during the period before/after culture among patients with ABR or MDR ESKAPE organisms were included. The costs were converted into 2015 United States Dollars. Disagreements were resolved by a third reviewer.


          Of 13,693 studies identified, 83 eligible studies were included in our review. The most studied organism was S. aureus, followed by Enterococcus, A. baumannii, E. coli, E. coli or/and K. pneumoniae, P. aeruginosa, and K. pneumoniae. There were 71 studies on total hospital cost or charge, 12 on antibiotic cost, 11 on hospital cost or charge after culture, 4 on ICU cost, 2 on hospital cost or charge before culture, and 2 on total direct and indirect cost. In general, ABR or MDR ESKAPE organisms are significantly associated with higher economic burden than those with susceptible organisms or those without infection or colonization. Nonetheless, there were no differences in a few studies between the two groups on total hospital cost or charge (16 studies), antibiotic cost (one study), hospital cost before culture (one study), hospital cost after culture (one study). Even, one reported that costs associated with MSSA infection were higher than the costs for similar MRSA cases.


          ABR in ESKAPE organisms is not always, but usually, associated with significantly higher economic burden. The results without significant differences may lack statistical power to detect a significant association. In addition, study design which controls for severity of illness and same empirical antibiotic therapy in the two groups would be expected to bias the study towards a similar, even negative result. The review also highlights key areas where further research is needed.

          Electronic supplementary material

          The online version of this article (10.1186/s13756-019-0590-7) contains supplementary material, which is available to authorized users.

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          Estimating the burden of antimicrobial resistance: a systematic literature review

          Background Accurate estimates of the burden of antimicrobial resistance (AMR) are needed to establish the magnitude of this global threat in terms of both health and cost, and to paramaterise cost-effectiveness evaluations of interventions aiming to tackle the problem. This review aimed to establish the alternative methodologies used in estimating AMR burden in order to appraise the current evidence base. Methods MEDLINE, EMBASE, Scopus, EconLit, PubMed and grey literature were searched. English language studies evaluating the impact of AMR (from any microbe) on patient, payer/provider and economic burden published between January 2013 and December 2015 were included. Independent screening of title/abstracts followed by full texts was performed using pre-specified criteria. A study quality score (from zero to one) was derived using Newcastle-Ottawa and Philips checklists. Extracted study data were used to compare study method and resulting burden estimate, according to perspective. Monetary costs were converted into 2013 USD. Results Out of 5187 unique retrievals, 214 studies were included. One hundred eighty-seven studies estimated patient health, 75 studies estimated payer/provider and 11 studies estimated economic burden. 64% of included studies were single centre. The majority of studies estimating patient or provider/payer burden used regression techniques. 48% of studies estimating mortality burden found a significant impact from resistance, excess healthcare system costs ranged from non-significance to $1 billion per year, whilst economic burden ranged from $21,832 per case to over $3 trillion in GDP loss. Median quality scores (interquartile range) for patient, payer/provider and economic burden studies were 0.67 (0.56-0.67), 0.56 (0.46-0.67) and 0.53 (0.44-0.60) respectively. Conclusions This study highlights what methodological assumptions and biases can occur dependent on chosen outcome and perspective. Currently, there is considerable variability in burden estimates, which can lead in-turn to inaccurate intervention evaluations and poor policy/investment decisions. Future research should utilise the recommendations presented in this review. Trial registration This systematic review is registered with PROSPERO (PROSPERO CRD42016037510). Electronic supplementary material The online version of this article (10.1186/s13756-018-0336-y) contains supplementary material, which is available to authorized users.
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            The impact of methicillin resistance in Staphylococcus aureus bacteremia on patient outcomes: mortality, length of stay, and hospital charges.

            To evaluate the impact of methicillin resistance in Staphylococcus aureus on mortality, length of hospitalization, and hospital charges. A cohort study of patients admitted to the hospital between July 1, 1997, and June 1, 2000, who had clinically significant S. aureus bloodstream infections. A 630-bed, urban, tertiary-care teaching hospital in Boston, Massachusetts. Three hundred forty-eight patients with S. aureus bacteremia were studied; 96 patients had methicillin-resistant S. aureus (MRSA). Patients with methicillin-susceptible S. aureus (MSSA) and MRSA were similar regarding gender, percentage of nosocomial acquisition, length of hospitalization, ICU admission, and surgery before S. aureus bacteremia. They differed regarding age, comorbidities, and illness severity score. Similar numbers of MRSA and MSSA patients died (22.9% vs 19.8%; P = .53). Both the median length of hospitalization after S. aureus bacteremia for patients who survived and the median hospital charges after S. aureus bacteremia were significantly increased in MRSA patients (7 vs 9 days, P = .045; 19,212 dollars vs 26,424 dollars, P = .008). After multivariable analysis, compared with MSSA bacteremia, MRSA bacteremia remained associated with increased length of hospitalization (1.29 fold; P = .016) and hospital charges (1.36 fold; P = .017). MRSA bacteremia had a median attributable length of stay of 2 days and a median attributable hospital charge of 6916 dollars. Methicillin resistance in S. aureus bacteremia is associated with significant increases in length of hospitalization and hospital charges.
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              Clinical and economic impact of common multidrug-resistant gram-negative bacilli.


                Author and article information

                +8657188206098 , donghj@zju.edu.cn
                Antimicrob Resist Infect Control
                Antimicrob Resist Infect Control
                Antimicrobial Resistance and Infection Control
                BioMed Central (London )
                13 August 2019
                13 August 2019
                : 8
                : 137
                [1 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, Center for Health Policy Studies, School of Public Health, , Zhejiang University School of Medicine, ; 866 Yuhangtang Road, Hangzhou, 310058 Zhejiang China
                [2 ]ISNI 0000 0004 1937 0626, GRID grid.4714.6, Global Health-Health Systems and Policy (HSP): Medicines, focusing antibiotics, Department of Public Health Sciences, , Karolinska Institutet, ; Stockholm, Sweden
                [3 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, The Fourth Affiliated Hospital Zhejiang University School of Medicine, ; No. N1, Shancheng Avenue, Yiwu City, Zhejiang China
                Author information
                © The Author(s). 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.

                : 23 March 2019
                : 31 July 2019
                Funded by: FundRef http://dx.doi.org/10.13039/501100004543, China Scholarship Council;
                Award ID: 201806320172
                Award Recipient :
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                © The Author(s) 2019

                Infectious disease & Microbiology
                antibiotic resistance,economic burden,eskape organism,s. aureus,enterococcus,a. baumannii,e. coli,k. pneumoniae,p. aeruginosa


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