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      Protocol for a systematic review of time to antibiotics (TTA) in patients with fever and neutropenia during chemotherapy for cancer (FN) and interventions aiming to reduce TTA

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          Abstract

          Background

          Fever and neutropenia (FN) is a common complication of chemotherapy for cancer. Prompt empiric broad-spectrum antibiotic therapy in FN is typically considered standard of care, but the definition of prompt is not clear. We seek to systematically review the available data on the association between time to antibiotics (TTA) administration and clinical outcomes in patients with FN being treated with chemotherapy. There have been several efforts to reduce TTA in patients with FN, by implementing specific interventions, presuming there will be a beneficial effect on patient-important outcomes. This systematic review will also collect data on such interventions and their effect to reduce TTA and potentially change clinical outcomes.

          Methods/design

          The search will cover MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CINAHL, CDSR, CENTRAL, and LILACS. A full-search strategy is provided. Lists of studies identified by references cited and forward citation searching of included articles will also be reviewed. Studies will be screened, and data extracted by one researcher and independently checked by a second. Confounding biases and quality of studies will be assessed with the risk of bias in non-randomised studies-of interventions (ROBINS-I) tool.

          Data will be presented in narrative and tabular forms; in addition, if appropriate data is available, random effects meta-analysis will be used to examine TTA.

          A detailed analysis plan, including an assessment of heterogeneity and publication bias, is provided.

          Discussion

          This study aims to evaluate the association between TTA and patient-important clinical outcomes. Additionally, it will identify, critically appraise, and synthesise information on performed interventions and its effect to reduce TTA as a way of gaining insight into the potential use of these approaches. This will provide better knowledge for an adjusted treatment approach of FN.

          Systematic review registration

          PROSPERO [ CRD42018092948]

          Electronic supplementary material

          The online version of this article (10.1186/s13643-019-1006-8) contains supplementary material, which is available to authorized users.

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          Most cited references19

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          Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia.

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            Management of febrile neutropaenia: ESMO Clinical Practice Guidelines.

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              Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update.

              Purpose To update a clinical practice guideline (CPG) for the empirical management of fever and neutropenia (FN) in children with cancer and hematopoietic stem-cell transplantation recipients. Methods The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group of experts in pediatric oncology and infectious diseases that includes a patient advocate. For questions of risk stratification and evaluation, we updated systematic reviews of observational studies. For questions of therapy, we conducted a systematic review of randomized trials of any intervention applied for the empirical management of pediatric FN. The Grading of Recommendation Assessment, Development and Evaluation approach was used to make strong or weak recommendations and to classify levels of evidence as high, moderate, low, or very low. Results Recommendations related to initial presentation, ongoing management, and empirical antifungal therapy of pediatric FN were reviewed; the most substantial changes were related to empirical antifungal therapy. Key differences from our 2012 FN CPG included the listing of a fourth-generation cephalosporin for empirical therapy in high-risk FN, refinement of risk stratification to define patients with high-risk invasive fungal disease (IFD), changes in recommended biomarkers and radiologic investigations for the evaluation of IFD in prolonged FN, and a weak recommendation to withhold empirical antifungal therapy in IFD low-risk patients with prolonged FN. Conclusion Changes to the updated FN CPG recommendations will likely influence the care of pediatric patients with cancer and those undergoing hematopoietic stem-cell transplantation. Future work should focus on closing research gaps and on identifying ways to facilitate implementation and adaptation.
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                Author and article information

                Contributors
                christa.koenig@insel.ch
                jess.morgan@york.ac.uk
                roland.ammann@insel.ch
                lillian.sung@sickkids.ca
                bob.phillips@york.ac.uk
                Journal
                Syst Rev
                Syst Rev
                Systematic Reviews
                BioMed Central (London )
                2046-4053
                3 April 2019
                3 April 2019
                2019
                : 8
                : 82
                Affiliations
                [1 ]ISNI 0000 0001 0726 5157, GRID grid.5734.5, Division of Pediatric Hematology/Oncology, Department of Pediatrics, Inselspital, Bern University Hospital, , University of Bern, ; Bern, Switzerland
                [2 ]ISNI 0000 0004 1936 9668, GRID grid.5685.e, Centre for Reviews and Dissemination, , University of York, ; York, UK
                [3 ]ISNI 0000 0001 2157 2938, GRID grid.17063.33, The Hospital for Sick Children, , University of Toronto, ; Toronto, Ontario Canada
                [4 ]Leeds Children’s Hospital, Leeds, UK
                Author information
                http://orcid.org/0000-0002-9965-5183
                Article
                1006
                10.1186/s13643-019-1006-8
                6446276
                30944024
                4408ca71-9ab0-4751-b1f7-35c3d634d5cd
                © The Author(s). 2019

                Open AccessThis 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.

                History
                : 16 July 2018
                : 25 March 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004361, Krebsliga Schweiz;
                Award ID: KFS-3645-02-2015
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000272, National Institute for Health Research;
                Categories
                Protocol
                Custom metadata
                © The Author(s) 2019

                Public health
                fever,neutropenia,cancer,time to antibiotics
                Public health
                fever, neutropenia, cancer, time to antibiotics

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