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For this review, 78 publications for use of fluconazole in children below 1 year of age were evaluated with a total of 726 patients. The range of fluconazole dosage was 2-50 mg/kg/day with 162 days as maximum duration of treatment. According to the present experience, fluconazole seems to be an efficacious and well tolerated therapy against systemic candidosis and candidemia in children below 1 year of age, including neonates and very low birth-weight infants (VLBWI). The recommended daily dosage is 6 mg/kg. In patients with impaired renal function, the daily dose should be reduced in accordance with the guidelines given for adults. In neonates during the first two weeks of life, this dosage should be administered only every 72 hours. In weeks two to four of life, the same dose should be given every 48 hours. After that daily dosing is appropriate. This posology is derived from the age-related pharmacokinetics of fluconazole with a higher volume of distribution and a prolonged plasma elimination half life especially during the first month of life. Drug monitoring during treatment should be performed to ensure therapeutic plasma concentrations of fluconazole within a range between 4 and 20 micrograms/ml. The benefit of fluconazole should be investigated in prospective studies for treatment of systemic candidosis with administration of higher dosages as well as for early empiric therapy in VLBWI.

Zusammenfassung. Aus der Hefepilzkolonisation des Darmtraktes ergeben sich fur die therapeutische und prophylaktische Anwendung von Polyenantimykotika (Nystatin, Amphotericin B) unterschiedliche Konsequenzen: Abwehrgeschadigten, neutropenischen Patienten sollten sie langfristig wahrend erhohter Mykoserisiken verabreicht werden. Die Dosierung richtet sich nach dem Alter, der Funktionstuchtigkeit des Gastrointestinaltraktes und dem Grundleiden des Patienten. Beim abwehrkompetenten Menschen sollte dagegen die kommensale Hefepilzfiora nicht ohne klinische Indikation medikamentos unterdruckt werden, da eine dauerhafte Eradikation von Hefen im Darmtrakt nicht moglich ist. Die Pilze treten — wenn auch zunachst in geringer Menge — etwa 5–14 Tage nach Therapieende erneut in den Faeces auf. Der Einflus oral applizierter Polyenantimykotika last sich im Darmlumen nach kurzer Zeit beobachten. Nystatin- und Amphotericin-B-Spiegel liegen ab 2., spatestens 3. Tag kontinuierlich wahrend der Verabreichung und maximal 10 Tage nach Therapieende in effektiven Konzentrationen im Stuhl vor. Parallel dazu ist das Vorkommen von Hefen in den Faeces deutlich vermindert oder unter die Nachweisgrenze von Pilzkulturen gesunken. Eine langfristige orale Anwendung von Polyenantimykotika bei unklaren klinischen Beschwerden abwehrkompetenter Patienten ohne massiven intestinalen Hefepilzbefall ist nicht gerechtfertigt. Summary. On the basis of intestinal yeast colonization different consequences for therapeutic and prophylactic administration of polyene antimycotics have to be drawn. Immunocompromised neutropenic patients should orally receive polyene antifungal drugs (nystatin or amphotericin B) for a long time during the period of increased risk for systemic candidosis. The level of daily dosing is dependent on age, physiological status of the gastrointestinal tract, and underlying disease of the patient. In immunocompetent persons the normal commensal yeast flora should not be suppressed by antifungal chemoprophylaxis if no clinical indications are present, because permanent eradication of yeast in the intestinal tract ist not attainable. About 5 to 15 days after finishing the administration of polyene antimycotics the fungi are detectable again in the faeces in low quantities. The influence of orally administered polyene drugs in the intestinal tract may be detected shortly after starting the application. Thus efficient concentrations of nystatin and amphotericin B are continuously present in the faeces 24 to 48 hours after beginning until 2 to 10 days after finishing the administration. During this time the quantity of yeast in the faeces is evidently reduced or not longer detectable by fungal culture. The oral administration of polyene antimycotics for a long

Zusammenfassung. Es wird der Verlauf einer Meningoenzephalitis durch Cryptococcus neoformans bei einer 14jahrigen Patientin dargelegt. Die mykologischen Untersuchungsbefunde wiesen anfangs einen massiven Befall des Liquors mit Cryptococcus neoformans (ca. 10000 Hefezellen/ml) und wochenlang sehr hohe Cryptococcus-Antigentiter (maximal 1:2048) aus. Eine HIV-Infektion oder andere schwerwiegende Immundefekte konnten ausgeschlossen werden. Die Behandlung der Cryptococcose erfolgte mit der Dreifachkombination Amphotericin B, Flucytosin und Fluconazol. Der Liquor konnte saniert werden. Trotzdem kam es zu erheblichen Lasionen am Gehirn. Die Patientin ist an den Folgen der Pilzinfektion am 74. Behandlungstag verstorben. Der geschilderte Krankheitsverlauf ist Anlas, auf die Differentialdiagnose, Cryptococcus neoformans-Infektion“bei der chronischen lymphozytaren Liquorpleozytose, verbunden mit Hirndruck- und Augensymptomen, hinzuweisen. Summary. Case report on a lethal meningo-encephalitis due to Cryptococcus neoformans in a 14-year-old girl without serious immunodeficiency inclusive HIV-infection. The detection of high quantities of cells of Cryptococcus neoformans (about 10000/ml) and high levels of Cryptococcus antigen (up to 1:2048) in the cerebrospinal fluid are remarkable. The patient was treated with a triple combination of amphotericin B, flucytosine and fluconazole. After 18 days the cerebrospinal fluid was sterile. Nevertheless considerable lesions of the brain arised. The patient died from the Cryptococcus infection on day 74 of the antimycotic therapy. Cryptococcosis should be included into the differential diagnosis of the chronic lymphocytic pleocytosis of the cerebrospinal fluid connected with symptoms of intracranial pressure and ocular symptoms.

Case report on a lethal meningo-encephalitis due to Cryptococcus neoformans in a 14-year-old girl without serious immunodeficiency inclusive HIV-infection. The detection of high quantities of cells of Cryptococcus neoformans (about 10,000/ml) and high levels of Cryptococcus antigen (up to 1:2048) in the cerebrospinal fluid are remarkable. The patient was treated with a triple combination of amphotericin B, flucytosine and fluconazole. After 18 days the cerebrospinal fluid was sterile. Nevertheless considerable lesions of the brain arised. The patient died from the Cryptococcus infection on day 74 of the antimycotic therapy. Cryptococcosis should be included into the differential diagnosis of the chronic lymphocytic pleocytosis of the cerebrospinal fluid connected with symptoms of intracranial pressure and ocular symptoms.

On the basis of intestinal yeast colonization different consequences for therapeutic and prophylactic administration of polyene antimycotics have to be drawn. Immunocompromised neutropenic patients should orally receive polyene antifungal drugs (nystatin or amphotericin B) for a long time during the period of increased risk for systemic candidosis. The level of daily dosing is dependent on age, physiological status of the gastrointestinal tract, and underlying disease of the patient. In immunocompetent persons the normal commensal yeast flora should not be suppressed by antifungal chemoprophylaxis if no clinical indications are present, because permanent eradication of yeast in the intestinal tract ist not attainable. About 5 to 15 days after finishing the administration of polyene antimycotics the fungi are detectable again in the faeces in low quantities. The influence of orally administered polyene drugs in the intestinal tract may be detected shortly after starting the application. Thus efficient concentrations of nystatin and amphotericin B are continuously present in the faeces 24 to 48 hours after beginning until 2 to 10 days after finishing the administration. During this time the quantity of yeast in the faeces is evidently reduced or not longer detectable by fungal culture. The oral administration of polyene antimycotics for a long time in persons without immunodepression and without heavy intestinal yeast colonization is not justified.

The aim of this study was to determine the efficacy of orally administered amphotericin B (Ampho B) on the elimination and suppression of yeasts in the orointestinal tract and on the clinical success regarding the Ampho B concentrations in faeces and serum. A total of 23 newborns at risk suffering from oral and/or cutaneous candidosis and massive colonization of yeasts in the orointestinal tract received Ampho-Moronal suspension (Squibb-Heyden, München) for 10 days: newborns1500 g 4 x 20 mg Ampho B/d and newborns1500 g 4 x 40 mg/d. Ampho B was detected in concentrations between 0.6 and 20 micrograms/g in the faeces of all patients 24 hours after beginning and 2-6 days after the end of the application. During this time Ampho B concentrations between 0.06 and 0.58 microgram/ml were also detected in the serum of the newborns. During the administration of Ampho-Moronal suspension for 10 days the initial available yeasts were eliminated in 18 patients (78%) out of the faeces. In 7 out of 17 patients (41%) the oral and cutaneous candidosis was cured. After finishing the administration of Ampho-Moronal Candida albicans was isolated again from the faeces during the following 5 days in half of the newborns who had reached negative mycological findings during the prophylaxis. For that reason Ampho-Moronal should be prophylactically administered for a longer time during the period of increased risk for systemic mycosis.