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      Guideline for Antibacterial Prophylaxis Administration in Pediatric Cancer and Hematopoietic Stem Cell Transplantation

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          Abstract

          Background

          Bacteremia and other invasive bacterial infections are common among children with cancer receiving intensive chemotherapy and in pediatric recipients of hematopoietic stem cell transplantation (HSCT). Systemic antibacterial prophylaxis is one approach that can be used to reduce the risk of these infections. Our purpose was to develop a clinical practice guideline (CPG) for systemic antibacterial prophylaxis administration in pediatric patients with cancer and those undergoing HSCT.

          Methods

          An international and multidisciplinary panel was convened with representation from pediatric hematology/oncology and HSCT, pediatric infectious diseases (including antibiotic stewardship), nursing, pharmacy, a patient advocate, and a CPG methodologist. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to generate recommendations based on the results of a systematic review of the literature.

          Results

          The systematic review identified 114 eligible randomized trials of antibiotic prophylaxis. The panel made a weak recommendation for systemic antibacterial prophylaxis for children receiving intensive chemotherapy for acute myeloid leukemia and relapsed acute lymphoblastic leukemia (ALL). Weak recommendations against the routine use of systemic antibacterial prophylaxis were made for children undergoing induction chemotherapy for ALL, autologous HSCT and allogeneic HSCT. A strong recommendation against its routine use was made for children whose therapy is not expected to result in prolonged severe neutropenia. If used, prophylaxis with levofloxacin was recommended during severe neutropenia.

          Conclusions

          We present a CPG for systemic antibacterial prophylaxis administration in pediatric cancer and HSCT patients. Future research should evaluate the long-term effectiveness and adverse effects of prophylaxis.

          Abstract

          This clinical practice guideline presents recommendations for systemic antibacterial prophylaxis administration in pediatric cancer and hematopoietic stem cell transplantation patients. The recommendations were developed by an international panel based on the results of a systematic review of 114 randomized trials.

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          Most cited references27

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          Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas.

          The role of prophylactic antibacterial agents after chemotherapy remains controversial. We conducted a randomized, double-blind, placebo-controlled trial in patients who were receiving cyclic chemotherapy for solid tumors or lymphoma and who were at risk for temporary, severe neutropenia (fewer than 500 neutrophils per cubic millimeter). Patients were randomly assigned to receive either 500 mg of levofloxacin once daily or matching placebo for seven days during the expected neutropenic period. The primary outcome was the incidence of clinically documented febrile episodes (temperature of more than 38 degrees C) attributed to infection. Secondary outcomes included the incidence of all probable infections, severe infections, and hospitalization but did not include a systematic evaluation of antibacterial resistance. A total of 1565 patients underwent randomization (784 to placebo and 781 to levofloxacin). The tumors included breast cancer (35.4 percent), lung cancer (22.5 percent), testicular cancer (14.4 percent), and lymphoma (12.8 percent). During the first cycle of chemotherapy, 3.5 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 7.9 percent in the placebo group (P<0.001). During the entire chemotherapy course, 10.8 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 15.2 percent of patients in the placebo group (P=0.01); the respective rates of probable infection were 34.2 percent and 41.5 percent (P=0.004). Hospitalization was required for the treatment of infection in 15.7 percent of patients in the levofloxacin group and 21.6 percent of patients in the placebo group (P=0.004). The respective rate of severe infection was 1.0 percent and 2.0 percent (P=0.15), with four infection-related deaths in each group. An organism was isolated in 9.2 percent of probable infections. Among patients receiving chemotherapy for solid tumors or lymphoma, the prophylactic use of levofloxacin reduces the incidence of fever, probable infection, and hospitalization. Copyright 2005 Massachusetts Medical Society.
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            Considerations when prescribing trimethoprim-sulfamethoxazole.

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              Effect of Levofloxacin Prophylaxis on Bacteremia in Children With Acute Leukemia or Undergoing Hematopoietic Stem Cell Transplantation

              Bacteremia causes considerable morbidity among children with acute leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). There are limited data on the effect of antibiotic prophylaxis in children.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press (US )
                1058-4838
                1537-6591
                01 July 2020
                02 November 2019
                02 November 2019
                : 71
                : 1
                : 226-236
                Affiliations
                [1 ] Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
                [2 ] Division of Infectious Diseases, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
                [3 ] Leeds Children’s Hospital, Leeds General Infirmary , Leeds Teaching Hospitals, NHS Trust, Leeds , United Kingdom
                [4 ] Centre for Reviews and Dissemination, University of York, Leeds West Yorkshire , United Kingdom
                [5 ] Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada
                [6 ] Division of Pediatric Hematology/Oncology, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
                [7 ] Columbia University/Herbert Irving Cancer Center, Pediatric Oncology , New York, New York, USA
                [8 ] Pediatric Oncology Institute, GRAACC/Federal University of Sao Paulo , Sao Paulo, Brazil
                [9 ] Infectious Diseases Unit, Department of Pediatrics, Istituto Giannina Gaslini, Genova, Italy
                [10 ] High Tor Limited, Nassau, Bahamas
                [11 ] Department of Pharmacy, The Hospital for Sick Children, and Leslie Dan Faculty of Pharmacy, University of Toronto , Toronto, Ontario, Canada
                [12 ] Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada
                [13 ] Infectious Disease Research Program, Center for Bone Marrow Transplantation, Department of Pediatric Hematology/Oncology, University Children’s Hospital, Muenster, Germany
                [14 ] Department of Infectious Diseases and Infection Prevention, Peter MacCallum Cancer Centre , Melbourne, Victoria, Australia
                [15 ] The Sir Peter MacCallum Department of Oncology, National Centre for Infections in Cancer, University of Melbourne, Melbourne, Victoria, Australia
                [16 ] Department of Pediatrics, Hospital Luis Calvo Mackenna, Faculty of Medicine, Universidad de Chile, Santiago, Chile
                [17 ] Duke University Medical Center, Pediatric Infectious Diseases, Durham, North Carolina, USA
                [18 ] Department of Pediatric Oncology, Princess Maxima Centre, Utrecht, Netherlands
                [19 ] Division of Infectious Diseases, St Jude’s Children’s Research Hospital, Memphis, Tennessee, USA
                [20 ] Pediatric Oncology Group of Ontario, Toronto, Ontario, Canada
                Author notes
                Correspondence: L. Sung, Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G1X8 Canada ( lillian.sung@ 123456sickkids.ca ).
                Article
                ciz1082
                10.1093/cid/ciz1082
                7312235
                31676904
                92c3e334-f579-4c3e-b4bc-152ed38b3b5b
                © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 26 August 2019
                : 29 October 2019
                : 22 October 2019
                : 13 December 2019
                Page count
                Pages: 11
                Funding
                Funded by: Pediatric Oncology Group of Ontario, DOI 10.13039/501100000163;
                Funded by: Canada Research Chair in Pediatric Oncology Supportive Care;
                Categories
                Review Article
                AcademicSubjects/MED00290

                Infectious disease & Microbiology
                practice guideline,bacterial infection,prevention,pediatric oncology,hematopoietic stem cell transplantation

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