Empfehlungen zur Diagnostik und Therapie bei krebskranken Kindern mit Fieber und Neutropenie – Vergleich zweier aktueller Leitlinien

Zusammenfassung

Krebskranke Kinder und Jugendliche haben aufgrund der Beeinträchtigung ihres Immunsystems ein erhöhtes Risiko für Infektionen. Die Neutropenie ist der wichtigste Risikofaktor für infektiöse Komplikationen, und Fieber in der Neutropenie stellt einen pädiatrischen Notfall dar. Während für Erwachsene mit Fieber in der Neutropenie bereits seit langem Leitlinien existieren, finden sich eigene Leitlinien für Kinder und Jugendliche erst seit wenigen Jahren. Sie sind von Bedeutung, da pädiatrische Patienten sich von Erwachsenen in vielen Punkten wie Grunderkrankung, Komorbidität sowie verfügbare Arzneimittel unterscheiden. Im vorliegenden Artikel werden die wichtigsten Gemeinsamkeiten und Unterschiede der jüngst erschienenen interdisziplinären Leitlinie der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI) und Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) sowie einer Leitlinie eines internationalen Expertenpanels für Kinder mit Fieber und Neutropenie herausgearbeitet und diskutiert.

Abstract

Immunocompromised children and adolescents receiving treatment for cancer have a considerably increased risk for infection. Neutropenia is the most important single risk factor for infectious complications, and fever in neutropenia is considered as an emergency. Whereas guidelines for the management of fever in neutropenic adults have been established for decades, specific pediatric guidelines have not been developed until recently. As children differ in many aspects from adults such as in the underlying malignancy or in the availability and dosing of antimicrobial compounds, guidelines for pediatric patients are important. This article reviews similarities and differences between the recently published German interdisciplinary guideline of the German Societies of Pediatric Infectious Diseases and Pediatric Oncology and Hematology and a guideline developed by a panel of international experts for the management of fever in neutropenia in children and adolescents.

Schlüsselwörter

Kind - Krebserkrankung - Neutropenie Fieber - antimikrobielle Therapie

Key words

child - cancer - neutropenia - fever - antimicrobial therapy

• Literatur

• 1 Bodey GP, Buckley M, Sathe YS. et al. Quantitative relationships between circulating leukocytes and infections in patients with acute leukemia. Ann Intern Med 1966; 64: 328-340
• 2 Bosk A, Groll AH, Hufnagel M. et al. Leitlinie Sepsis bei Kindern jenseits der Neonatalperiode. AWMF Leitlinie 024 - 025 2015 DOI.
• 3 Brozek JL, Akl EA, Alonso-Coello P. et al. Grading quality of evidence and strength of recommendations in clinical practice guidelines. Part 1 of 3. An overview of the GRADE approach and grading quality of evidence about interventions. Allergy 2009; 64: 669-677
• 4 Burgos A, Zaoutis TE, Dvorak CC. et al. Pediatric invasive aspergillosis: a multicenter retrospective analysis of 139 contemporary cases. Pediatrics 2008; 121: e1286-e1294
• 5 Caselli D, Cesaro S, Ziino O. et al. A prospective, randomized study of empirical antifungal therapy for the treatment of chemotherapy-induced febrile neutropenia in children. Br J Haematol 2012; 158: 249-255
• 6 Groll AH, Castagnola E, Cesaro S. et al. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncol 2014; 15: e327-e340
• 7 Hughes WT, Armstrong D, Bodey GP. et al. Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. J Infect Dis 1990; 161: 381-396
• 8 Lehrnbecher T, Ethier MC, Zaoutis T. et al. International variations in infection supportive care practices for paediatric patients with acute myeloid leukaemia. Br J Haematol 2009; 147: 125-128
• 9 Lehrnbecher T, Foster C, Vazquez N. et al. Therapy-induced alterations in host defense in children receiving therapy for cancer. J Pediatr Hematol Oncol 1997; 19: 399-417
• 10 Lehrnbecher T, Koehl U, Wittekindt B. et al. Changes in host defence induced by malignancies and antineoplastic treatment: implication for immunotherapeutic strategies. Lancet Oncol 2008; 9: 269-278
• 11 Lehrnbecher T, Phillips R, Alexander S. et al. Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. J Clin Oncol 2012; 30: 4427-4438
• 12 Lehrnbecher T, Robinson P, Fisher B. et al. Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update. J Clin Oncol 2017; 35: 2082-2094
• 13 Lehrnbecher T, Robinson PD, Fisher BT. et al. Galactomannan, beta-D-Glucan, and Polymerase Chain Reaction-Based Assays for the Diagnosis of Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis. Clin Infect Dis 2016; 63: 1340-1348
• 14 Link H, Bohme A, Cornely OA. et al. Antimicrobial therapy of unexplained fever in neutropenic patients – guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO), Study Group Interventional Therapy of Unexplained Fever, Arbeitsgemeinschaft Supportivmassnahmen in der Onkologie (ASO) of the Deutsche Krebsgesellschaft (DKG-German Cancer Society). Ann Hematol 2003; 82 (Suppl. 02) S105-S117
• 15 Pizzo PA. Infectious complications in the child with cancer. I. Pathophysiology of the compromised host and the initial evaluation and management of the febrile cancer patient. J Pediatr 1981; 98: 341-354
• 16 Science M, Robinson PD, MacDonald T. et al. Guideline for primary antifungal prophylaxis for pediatric patients with cancer or hematopoietic stem cell transplant recipients. Pediatr Blood Cancer 2014; 61: 393-400
• 17 Simon A, Agyeman P, Ammann R. et al. Diagnostik und Therapie bei Kindern mit onkologischer Grunderkrankung, Fieber und Granulozytopenie (mit febriler Neutropenie) außerhalb der allogenen Stammzelltransplantation. AWMF Leitlinie 048/14 2016 DOI
• 18 Sung L, Phillips R, Lehrnbecher T. Time for paediatric febrile neutropenia guidelines – children are not little adults. Eur J Cancer 2011; 47: 811-813