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      Antifungal stewardship in critical care: Implementing a diagnostics-driven care pathway in the management of invasive candidiasis

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          Summary

          Background

          Invasive candidiasis (IC) is the most common invasive fungal disease in patients admitted to critical care and is associated with high mortality rates. Diagnosis can be delayed by the poor sensitivity of culture-based methods, leading to unnecessary use of empirical antifungal therapy (EAFT). The fungal biomarker (1–3)-β-d-glucan (BDG) has been shown to aid in the diagnosis of IC in critical care and has been incorporated into antifungal stewardship (AFS) programmes.

          Aim

          To describe our experience using a diagnostics-driven AFS programme incorporating the fungal biomarker BDG, analyse its impact on antifungal therapy (AFT), and gain an improved understanding of the epidemiology of IC in our critical care unit (CrCU).

          Methods

          An AFS care pathway incorporating BDG was introduced in the CrCU in St James's Hospital, Dublin. Following an educational programme, compliance with the pathway was prospectively audited between December 1st, 2017 and July 31 st, 2018.

          Results and Conclusion

          One hundred and nine AFT episodes were included, of which 95 (87%) had a BDG sent. Of those with BDG results available at the time of decision-making, 38 (63%) were managed in accordance with the care pathway. In compliant episodes without IC, median EAFT duration was 5.5 days [IQR 4–7] and no increase in mortality or subsequent IC was observed. Although adopting a diagnostics-driven approach was found to be useful in the cohort of patients with BDG results available, the use of once-weekly BDG testing did not result in an observed reduction in the consumption of anidulafungin, highlighting an important limitation of this approach.

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          Most cited references20

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          Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.

          It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
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            Finding the "missing 50%" of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care.

            Blood cultures are limited for diagnosing invasive candidiasis by poor sensitivity and slow turn-around time. New diagnostics are needed to complement cultures, in particular to identify the "missing 50%" of patients who are blood culture-negative. Mannan/anti-mannan immunoglobulin G, β-D-glucan (BDG) and polymerase chain reaction (PCR) assays can diagnose candidemia before blood cultures and show promising sensitivity/specificity, but they are not widely investigated in blood culture-negative, deep-seated candidiasis. In a recent study, BDG and PCR were superior to blood cultures in deep-seated candidiasis, suggesting they may identify currently undiagnosed patients and expand our understanding of disease spectrum. Positive predictive values of nonculture tests are limited by the low prevalence of invasive candidiasis, which mandates that results be interpreted judiciously. When used as biomarkers that assess a patient's risk of having invasive candidiasis, tests will facilitate preemptive antifungal strategies. Because negative predictive values are excellent, tests will also be useful for ruling out invasive candidiasis and discontinuing unnecessary antifungal therapy.
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              Systematic Review and Meta-analysis of Clinical and Economic Outcomes from the Implementation of Hospital-Based Antimicrobial Stewardship Programs.

              The implementation of antimicrobial stewardship programs (ASPs) is a promising strategy to help address the problem of antimicrobial resistance. We sought to determine the efficacy of ASPs and their effect on clinical and economic parameters. We searched PubMed, EMBASE, and Google Scholar looking for studies on the efficacy of ASPs in hospitals. Based on 26 studies (extracted from 24,917 citations) with pre- and postimplementation periods from 6 months to 3 years, the pooled percentage change of total antimicrobial consumption after the implementation of ASPs was -19.1% (95% confidence interval [CI] = -30.1 to -7.5), and the use of restricted antimicrobial agents decreased by -26.6% (95% CI = -52.3 to -0.8). Interestingly, in intensive care units, the decrease in antimicrobial consumption was -39.5% (95% CI = -72.5 to -6.4). The use of broad-spectrum antibiotics (-18.5% [95% CI = -32 to -5.0] for carbapenems and -14.7% [95% CI = -27.7 to -1.7] for glycopeptides), the overall antimicrobial cost (-33.9% [95% CI = -42.0 to -25.9]), and the hospital length of stay (-8.9% [95% CI = -12.8 to -5]) decreased. Among hospital pathogens, the implementation of ASPs was associated with a decrease in infections due to methicillin-resistant Staphylococcus aureus (risk difference [RD] = -0.017 [95% CI = -0.029 to -0.005]), imipenem-resistant Pseudomonas aeruginosa (RD = -0.079 [95% CI = -0.114 to -0.040]), and extended-spectrum beta-lactamase Klebsiella spp. (RD = -0.104 [95% CI = -0.153 to -0.055]). Notably, these improvements were not associated with adverse outcomes, since the all-cause, infection-related 30-day mortality and infection rates were not significantly different after implementation of an ASP (RD = -0.001 [95% CI = -0.009 to 0.006], RD = -0.005 [95% CI = -0.016 to 0.007], and RD = -0.045% [95% CI = -0.241 to 0.150], respectively). Hospital ASPs result in significant decreases in antimicrobial consumption and cost, and the benefit is higher in the critical care setting. Infections due to specific antimicrobial-resistant pathogens and the overall hospital length of stay are improved as well. Future studies should focus on the sustainability of these outcomes and evaluate potential beneficial long-term effects of ASPs in mortality and infection rates.
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                Author and article information

                Contributors
                Journal
                Infect Prev Pract
                Infect Prev Pract
                Infection Prevention in Practice
                Elsevier
                2590-0889
                19 February 2020
                June 2020
                19 February 2020
                : 2
                : 2
                : 100047
                Affiliations
                [a ]Department of Microbiology, St James's Hospital, Dublin, Ireland
                [b ]Pharmacy Department, St James's Hospital, Dublin, Ireland
                [c ]Department of Critical Care and Anaesthesia, St James's Hospital, Dublin, Ireland
                [d ]Department of Infectious Disease, Mater Misericordiae University Hospital, Dublin, Eccles St, Dublin, Ireland
                [e ]Department of Clinical Microbiology, Trinity College Dublin, Ireland
                Author notes
                []Corresponding author. Daniel Hare, Specialist Registrar in Clinical Microbiology, St. James's Hospital, Dublin. Ireland. danielhare5000@ 123456gmail.com
                Article
                S2590-0889(20)30011-1 100047
                10.1016/j.infpip.2020.100047
                8336030
                34368697
                269d14d8-a06d-4afb-886f-3b4575d3ada7
                © 2020 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 13 November 2019
                : 8 February 2020
                Categories
                Clinical Audits/Service Improvements

                antifungal stewardship,critical care,invasive fungal disease,fungal biomarkers,(1–3)-β-d-glucan

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