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.