The Effect of Cilofungin (LY 121019) in Combination with Amphotericin B or Flucytosine Against Candida Species: Die Wirkung von Cilofungin (LY 121019) in Kombination mit Amphotericin B oder Flucytosin auf Candida-Arten

Cilofungin was combined with amphotericin B or flucytosine to determine if synergistic inhibition or killing occurred against 50 strains of various Candida species. Synergistic inhibition of growth occurred only once with amphotericin B and cilofungin and only 2 times with flucytosine and cilofungin. Synergistic killing occurred in 5 strains with the amphotericin B-cilofungin combination and in 7 strains with the flucytosine-cilofungin combination. Antagonism occurred frequently with both the amphotericin B-cilofungin and the flucytosine-cilofungin combinations.     

In vitro and in vivo activity of antifungal agents in combination with fleroxacin, a new quinolone

The in vitro and in vivo interaction of fleroxacin with amphotericin B (Amph B), flucytosine (5-FC) and azoles against Candida albicans strains was tested. In vitro the interaction between fleroxacin and various antifungals was not dependent on the incubation time. Fleroxacin neither enhances nor antagonizes the in vitro activity of Amph B at high concentration (50-100 micrograms/ml). Fleroxacin has a synergistic effect with ketoconazole (KETO), but this is not observed with itraconazole (ITRA) or fluconazole (FLU). In no instance antagonism was observed. The activity of 5-FC was antagonized by fleroxacin being generally reduced by 2-4 dilution steps. In murine candidosis the efficacies of all antifungal drugs were not influenced by addition of 100 mg/kg fleroxacin. Therefore, the effects seen in in vitro tests are most probably not relevant for the clinical use of a combination of fleroxacin with antifungal drugs.     

酵母菌药敏试验常量与微量液体稀释法的比较

目的：采用常量和微量稀释法检测酵母样菌对四种抗真菌药物的最低抑菌浓度（MIC）,并将两种方法的MIC结果进行统计分析。方法：参照美国临床实验室标准化委员会（NCCLS）推荐的“酵母菌液体稀释法抗真菌药敏试验参考方法”,测定临床分离的20株酵母样菌,结果：两性霉素－B的两种方法对所有菌标的MIC值大多数落在两个稀释度范围内,但两种方法比较,多数MIC值≥两个稀释度。氟胞嘧啶对白色念珠菌、新型隐球菌和光滑球拟酵母菌两种方法中的MIC有90％得到相同的结果,两性霉素－B对有菌株、酮康唑对新型隐球菌两种方法有显著性差异（P＜0．05）。微量法中新型隐球菌在48h可以判定结果常量法要72h才能判定结果,结论：通过两种方法的比较及统计分析表明,微量法与常量法有较好的相关性,微量法操作简便,节省试剂和药物,适合临床实验室应用。     

A New Experimental Model of Localized Candidosis for the Study of Antifungal Chemotherapy Ein neues Experimentalmodell der lokalisierten Candidose zum Studium der antifungalen Chemotherapie

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed and was used to test the efficacy of various antifungal drugs. The results were similar regardless whether cortisone or cyclophosphamide was used for immunosuppression. The highest efficacy was shown by amphotericin B in relatively high doses (2 mg/kg s.c.). The new triazole derivatives also showed good chemotherapeutic activity (fluconazole, ICI 195, 739, SDZ 89-485). Flucytosine was also highly effective despite its short half-life. The model thus gives a valuable indication of the chemotherapeutic efficacy against Candida thrush in humans.     

Tödliche Meningoenzephalitis durch Cryptococcus neoformans var. neoformans bei einem Mädchen ohne schwerwiegende Immundefekte

Zusammenfassung. Es wird der Verlauf einer Meningoenzephalitis durch Cryptococcus neoformans bei einer 14jährigen 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 Läsionen am Gehirn. Die Patientin ist an den Folgen der Pilzinfektion am 74. Behandlungstag verstorben. Der geschilderte Krankheitsverlauf ist Anlaß, auf die Differentialdiagnose, Cryptococcus neoformans -Infektion"bei der chronischen lymphozytären 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.