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DOI: 10.1055/s-2005-872501
© Georg Thieme Verlag Stuttgart · New York
Diagnose und Therapie von Pilzinfektionen und der Pneumozystis-Pneumonie bei Kindern und Jugendlichen mit neoplastischen Erkrankungen
Diagnosis and Management of Fungal Infections and Pneumocystis Pneumonitis in Pediatric Cancer PatientsPublication History
Publication Date:
15 November 2005 (online)
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Zusammenfassung
Invasive Pilzinfektionen sind eine wichtige Ursache von Morbidität und Mortalität krebskranker Kinder und Jugendlicher mit intensiv chemotherapeutisch behandelten hämatologischen Neoplasien und nach allogener hämatopoetischer Stammzelltransplantation. Die vorliegende Arbeit enthält umfassende Empfehlungen der Arbeitsgruppe „Infektionen bei immunsupprimierten Kindern” der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI) und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) zu Diagnose und Behandlung invasiver und oberflächlicher Pilzinfektionen sowie der Pneumocystis-jiroveci-Pneumonie. Sie basieren auf der speziellen Pharmakologie und dem Zulassungsstatus bei pädiatrischen Patienten sowie klinischen Studien, Fallserien und Expertenmeinungen analog den Evidenz-Kriterien der Infectious Diseases Society of America (IDSA). Die Empfehlungen für die häufigsten klinischen Entitäten sind hier zusammengefasst. Optionen zur Initialtherapie der unkomplizierten Candidämie umfassen Deoxycholat Amphotericin B (DAMB), Fluconazol (FLC), liposomales Amphotericin B (LAMB), die Kombination von DAMB plus FLC sowie Voriconazol (VCZ) für Patienten > 11 Jahre. Bei akuter disseminierter Candidiasis wird unverändert die Kombination von DAMB und Fluzytosin empfohlen. Zentralvenöse Katheter gelten als infektiöser Fokus und sollten wann immer möglich entfernt werden. Initialtherapie der Wahl bei vermuteten bzw. nachgewiesenen invasiven Aspergillus-Infektionen ist bei Patienten ab einem Alter von 12 Jahren VCZ. Alternativen sind DAMB und LAMB. Die Optionen für Patienten unter 12 Jahren sind im Wesentlichen auf DAMB und LAMB beschränkt. Aufgrund der bislang fehlenden Evidenz einer besseren Wirksamkeit und der noch nicht abgeschlossenen Dosisfindung von Caspofungin (CAS) sollte eine Kombinationstherapie (LAMB plus CAS bzw. VCZ plus CAS) nur bei fulminanten bzw. massiven, akut lebensbedrohlichen Infektionen erwogen werden. Bei Granulozytopenie wird die Gabe Kolonie-stimulierender Faktoren (G-CSF) empfohlen. Bei Immunsuppression sollten, wenn möglich, Glukokortikosteroide reduziert bzw. abgesetzt werden. Chirurgische Interventionen sind auf spezielle Indikationen beschränkt. Zygomykosen sind eine Indikation für hochdosiertes LAMB. Validierte Initialtherapie der Kryptokokken-Meningoenzephalitis ist die Kombination von DAMB plus Fluzytosin. Zur Behandlung der Pneumocystis jiroveci-Pneumonie wird Trimethoprim/Sulfamethoxazol bzw. Pentamidin empfohlen. Der Beitrag enthält über die genannten Entitäten hinaus eine Übersicht zur Pharmakokinetik und Dosierung antimykotischer Substanzen bei Kindern und Jugendlichen sowie detaillierte Diskussionen bzw. Empfehlungen zur empirischen antimykotischen Therapie, zur Resistenztestung, zur Diagnose und Therapie von oberflächlichen Pilzinfektionen, von invasiven Infektionen durch seltene und außereuropäische Pilzerreger und zu supportiven Therapiemaßnahmen auf der Basis der publizierten Literatur.
Abstract
Invasive fungal infections are important causes of morbidity and mortality in pediatric cancer patients with hematological malignancies and following allogeneic hematopoietic stem cell transplantation. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for diagnosis and treatment of fungal infections including Pneumocystis jiroveci. They are based on specific pediatric pharmacological and regulatory considerations and on the results of clinical trials, case series and expert opinions using the evidence criteria set forth by the Infectious Diseases Society of America (IDSA). Recommendations for the most frequent clinical entities are summarized here. Options for initial therapy of uncomplicated candidemia include deoxycholate amphotericin B (DAMB), fluconazole (FLC), liposomal amphotericin B (LAMB), the combination of DAMB plus FLC as well as voriconazole (VCZ) for patients > 11 years. For acute disseminated candidiasis, the combination of DAMB plus flucytosine is recommended. Indwelling central venous catheters serve as infectious nidus and should be removed whenever feasible. First-line therapy for presumed or proven invasive Aspergillus infections in patients 12 years and older is VCZ with DAMB and LAMB serving as alternatives. Choices for patients < 12 years of age are essentially limited to DAMB and LAMB. Due to the yet lacking evidence for enhanced antifungal efficacy and the ongoing dosage finding of caspofungin (CAS) in pediatric patients, combination therapies (LAMB plus CAS or VCZ plus CAS) should only be considered for fulminant or massive, life threatening infections. In granulocytopenic patients, adjunctive therapy with colony-stimulating factors (G-CSF) is recommended. In patients under immunosuppressive therapy, glucocorticosteroids ought to be reduced or discontinued, if feasible. Surgical interventions are restricted to specific indications. Zygomyces infections are an indication for high-dose LAMB. The combination of DAMB plus flucytosine is the initial treatment of choice of cryptococcal mengoencephalitis, and for treatment of Pneumocystis jiroveci pneumonitis, trimethoprim/sulfamethoxazol or intravenous pentamidine is recommended. Beyond the listed entities, the article provides a brief review on the pharmacokinetics and dosing of antifungal agents in children and adolescents as well as detailed discussions and evidence-based recommendations for empirical antifungal therapy, diagnosis and treatment of superficial fungal infections, of invasive infections by previously rare fungal pathogens and endemic moulds and for adjunctive immunomodulatory and surgical interventions.
Schlüsselwörter
maligne Erkrankungen - Stammzelltransplantation - Mykosen - Candida - Aspergillus - Zygomyces - Cryptococcus - Pneumozystis - Diagnose - Therapie - Amphotericin - Anidulafungin - Caspofungin - Fluconazol - Fluzytosin - Itraconazol - Micafungin - Posaconazol - Ravuconazol - Voriconazol
Key words
cancer - stem cell transplantation - mycoses - candida - aspergillus - zygomyces - cryptococcus - pneumocystis - diagnosis - treatment - amphotericin - anidulafungin - caspofungin - fluconazole - flucytosine - itraconazole - micafungin - posaconazole - ravuconazole - voriconazole - children
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