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 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pattern of amphotericin B toxicity was assessed retrospectively in a group of 20 children with cancer who had received one or more courses of the drug for treatment of systemic fungal infection. Azotemia was the most frequent complication, developing during 23 of 24 treatment courses. Other major toxic effects, in decreasing order of frequency, were anemia, hypokalemia, thrombocytopenia, and neutropenia. Infusion side effects, including drug-related fever, chills, and nausea, were also frequently seen. Seventeen of 20 patients were treated for disseminated histoplasmosis. Nineteen of 20 patients had acute leukemia. Although interaction with other agents could not be excluded, amphotericin B appeared to be the major causative agent for the toxic reactions noted. In no patient, however, was administration of amphotericin B stopped because of drug toxicity.
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PMID:Toxicity of amphotericin b in children with cancer. 46 22

Flucytosine is an antifungal agent useful in combination with amphotericin B in the treatment of several deeply invasive mycoses. The potentially dose-limiting, hematologic, gastrointestinal, and hepatic toxicities of flucytosine lead to a reluctance to use it in myelosuppressed patients. To investigate the safety and tolerability of flucytosine in this setting, we evaluated its use in 17 patients with cancer or aplastic anemia during a 2 1/2-year period at our institution and reviewed the literature describing mechanisms of action, resistance, in vitro and in vivo antifungal activity, clinical antifungal activity, pharmacokinetics, and toxicity. The combination of amphotericin B plus flucytosine eradicated the mycosis in 12 (71%) of 17 patients, whereas 3 (18%) of 17 died of progressive fungal infection. Serial serum levels of flucytosine measured by a creatinine iminohydrolase assay permitted reliable dosage adjustment. During therapy, only 2 (12%) of 17 patients had elevated mean serum levels of flucytosine (> 100 micrograms/mL) and 3 (18%) other patients had transiently elevated levels. Paired serum samples (n = 45) obtained at steady state during therapy with orally administered flucytosine showed similar peak and trough levels. Adverse effects of flucytosine therapy included one case each of reversible nausea, diarrhea, elevated transaminase levels, and thrombocytopenia. No cases of bone marrow aplasia, enterocolitis, hepatitis, or death due to flucytosine toxicity were encountered. We conclude that flucytosine in combination with amphotericin B is well tolerated in myelosuppressed patients when serum flucytosine levels are serially monitored.
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PMID:Evolving role of flucytosine in immunocompromised patients: new insights into safety, pharmacokinetics, and antifungal therapy. 145 31

A total of 43 patients, comprising 41 patients with oral candidiasis and 2 with esophageal candidiasis, were treated with miconazole (MCZ) gel to assess its efficacy and safety in treating upper digestive tract mycosis. The efficacy of the drug was evaluable in 33 of them, consisting of 32 patients with oral candidiasis and 1 with esophageal candidiasis. The clinical efficacy rate of the drug against oral candidiasis was 87.5% (28/32 patients), and the clinical response was good in the 1 evaluable patient with esophageal candidiasis. The safety of the drug was assessed in 40 patients. In 3 (7.5%) of them, nausea occurred as an adverse event, but was not particularly serious in any of them. No abnormal laboratory test values caused by the drug were observed. The results suggested that MCZ gel would be a very useful drug in treating oral and esophageal candidiasis.
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PMID:[Clinical effect of miconazole gel against upper digestive tract mycosis]. 188 Sep 14

During a period of 32 months (August 1986 until April 1989) 108 patients (74 women, 34 men; mean age 53 years) with neoplastic diseases (59 patients with solid tumors, 45 patients with lymphomas, two patients with acute leukaemias, one patient with chronic myelogenous leukaemia, one patient with aplastic anaemia) were studied in the Department of Internal Medicine of the University Erlangen-Nuremberg. Most were treated with a cytostatic chemotherapy. In order to prevent a mycotic infection in these immunocompromised patients, itraconazole, a new broad-spectrum antimycotic drug of the azole group, was given in an oral dosage of 100 mg day-1 (mean duration of prophylactic treatment 24 months). Localized Candida infections involving the oropharynx and the female genital organs were diagnosed in 16 patients (14.8%). Candida endophthalmitis occurred in one patient (0.9%). The serum concentration of Candida antibodies was significantly elevated in one patient (0.9%) without evidence of fungemia. Itraconazole had to be discontinued in four cases (3.7%) due to minor side effects of the drug (nausea, stomach complaints). Itraconazole appears to be a safe and effective antimycotic drug in long-term use in neutropenic patients.
Mycoses 1990 Jun
PMID:Prophylaxis of fungal infections with itraconazole in immunocompromised cancer patients. 217 92

The prophylactic and therapeutic effects of the oral administration of amphotericin B (AMPH) to patients with deep mycosis associated with hematologic diseases were evaluated in an investigation including determination of serum concentrations of the antibiotic. Prophylactic effects were examined in 111 subjects, and the efficacy rates averaged 83.8% at daily doses from 1,200 to 4,800 mg. The efficacy was significantly higher at a dose of 2,400 mg/day than at a dose of 1,200 mg/day (P less than 0.05). The efficacy rate tended to be higher when the length of administration period was 1 month or more. The percentage of the number of days of fever by neutrophil count was significantly less at a daily dose of 2,400 mg than at 1,200 mg in patients with neutrophil count of 1,000 cells/mm3 or less (P less than 0.001). The safety was evaluated in 131 subjects, and adverse effects were found in only 2 cases of nausea for an incidence rate of 1.5%. Therapeutic effects were studied in 12 cases, and efficacy rates averaged 58.3% at daily doses from 2,400 to 7,200 mg. Adverse effects consisted of 1 case of diarrhea among 15 subjects who were evaluated for the safety for an incidence rate of 6.7%. The serum concentrations of the antibiotic were examined in 60 of the prophylactic and therapeutic subjects. Average concentrations of AMPH at 4 hours after the first daily dose of 1,200, 2,400 and 4,800 mg were 0.040, 0.053 and 0.078 micrograms/ml, respectively. Concentrations gradually increased thereafter and reached averages of 0.089, 0.090 and 0.132 micrograms/ml, respectively, for the 3 dose levels on the 7th day. These results indicated that there were no serious adverse effects and serum concentrations were above the Candida MIC values at daily prophylactic and therapeutic doses of 1,200 to 7,200 mg of AMPH. Based on these findings, this drug can be expected to show prophylactic and therapeutic effects with safety in cases of deep mycosis.
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PMID:Prophylactic and therapeutic effects of oral administration of amphotericin B in mycosis associated with hematologic diseases. Study Group of Mycosis in Hematologic Disease. 219 13

Fluconazole, a novel triazole antifungal agent, was given orally or intravenously to 10 patients with pulmonary mycosis (7 patients with primary pulmonary cryptococcosis and 3 with pulmonary aspergillosis). Routes of administration were changed in some patients depending on their condition. Two patients from whom foci was removed by surgical operations were excluded from the efficacy assessment. Clinical efficacies in the remaining 8 patients were good in 2 cases and fair in 3 cases of pulmonary cryptococcosis; excellent in 1 case of pneumonia due to Aspergillus; and fair in 1 case and poor in the other case of pulmonary aspergilloma. Side reactions developed in 9 patients who received intravenous drip infusion were nausea or loss of appetite in 3 patients, fever and/or feverish sensation in 3, vascular pain in 1 and diarrhea and eruption in 1. In the patient who reported fever the drug was discontinued and in the patient who complained of pain at the site of injection, dosing was changed to the oral route but was discontinued due to elevated GOT, GPT, Al-P and gamma-GTP. Seven patients who received the drug orally did not report side effects except 2 patients. None of these side effects reported was serious and from the above results, fluconazole was considered to be a useful agent for the treatment of pulmonary mycosis.
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PMID:[Clinical efficacy of fluconazole in the patient with pulmonary mycosis]. 254 Mar 59

Fluconazole is a novel antifungal agent, available in oral and intravenous forms, which was developed by Pfizer Central Research. It is characterized by its long serum half-life (approximately 30 hours) to allow once-a-day dosing and favorable safety profile. Fluconazole was administered orally or intravenously to 166 patients with deep-seated mycosis and it was possible to evaluate clinical efficacies in 99 patients. Clinical cures were obtained in 41 (87.2%) out of 47 cases of candidiasis, in 10 (66.7%) out of 15 cases of cryptococcosis, in 17 (48.6%) out of 35 cases of aspergillosis and in 1 case each (100%) of mucormycosis and mycosis due to an unspecified yeast. Side effects were observed in 10 cases (rash 2, fever 2, abdominal discomfort 1, nausea 1, edema 1, edema/pleural effusion/oliguria 1, finger stiffness 1, hiccup 1) with incidence rate of 6.0%. Drug administrations were discontinued in 4 cases. In general, however, fluconazole was well tolerated. Abnormal changes in laboratory test values due to the drug were observed in 32 cases and incidence rate was 19.3%. These were, however, slight and temporary changes and most of them were in parameters of liver function. It is not clear if these changes were related to the fluconazole administration, because other drugs were concomitantly administered to these cases. These results indicate that fluconazole is an agent with very good potential for the treatment of the systemic deep-seated mycoses.
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PMID:[Clinical study of fluconazole on deep-seated fungal infections]. 254 Mar 69

The metabolic effects of the anti-fungal drug fluconazole were investigated in 18 women, 10 of whom were taking oral contraceptives, to examine whether this steroid antagonist has any effects primarily on hormone systems. The women, aged 29-40, took 50 mg fluconazole orally from Day 1 of their menstrual cycle for 21-28 days. Subjects kept a symptom diary, were tested weekly for hematological and liver function, and were checked for compliance by analyzing blood for drug by GLC. 5 women reported side effects: somnolence, dizziness, fatigue, increased appetite, headache (1) and nausea (1). No effects on liver function or menses were noted. The only significant findings were increases in serum thyroxine and testosterone in fluconazole-only subjects, and increases in insulin and apo-lipoprotein B in fluconazole-oral contraceptive subjects. Pills containing levonorgestrel were used by 9 women, desogestrel by 1. No significant differences were seen in estradiol, progesterone, sex-hormone-binding globulin, thyroid function, cortisol, glucose, C-peptide, cholesterol, triglycerides, lipoproteins. Thus it is unlikely that the short-term use of fluconazole for treatment of superficial mycoses, such as vulvovaginal candidiasis, will adversely affect steroid metabolism in women.
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PMID:Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives. 254 10

Between 1984 and 1987 14 patients with acute non-lymphocytic leukemia were treated with sequential high-dose cytosine arabinoside in combination with asparaginase. Twelve patients were suffering from refractory leukemia; in these patients complete remissions were achieved in 58%. The efficacy of this schedule was much better in patients with substantial leukemia cell reduction due to antecedent conventional therapy and no more than 25% blast cells in the bone marrow. In this subgroup complete remissions were achieved in 75% and 86% respectively, taking into account only the completed treatment courses. Beside the well-known side-effects such as alopecia, nausea, vomiting and hepatotoxicity, we observed an increase in severe infections. Three patients died of pulmonary mycosis.
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PMID:[Sequential high-dose cytarabine therapy in combination with asparaginase in acute myeloid leukemia]. 307 62

The ascites retention as a complication after ventriculo-peritoneal shunting (V-P shunt) is very rare. In this paper, a case of central nervous cryptococcosis giving rise to ascites after a V-P shunt is presented. A 45-year-old female was referred to Prefectural Gifu Hospital complaining of nausea and disturbance of recent memory. She had no remarkable medical history. CT scan films on admission showed enlarged ventricles except for the fourth ventricle, indicating an obstructed hydrocephalus. Lumbar cerebrospinal fluid (CSF) examinations revealed an increase in cell counts (mostly lymphocytes) and protein content, and positive Pandy and Nonne-Apelt reactions. Based on this information, it was tentatively suggested that she had a certain infection in the central nervous system such as mycosis or tuberculosis etc. Continuous ventricular drainage was performed for about three weeks. During this period, several lumbar and ventricular CSF cultures were negative. Therefore, a V-P shunt operation was performed. However, about seven weeks after the V-P shunt, she developed abdominal distention without any peritoneal signs. Abdominal CT scan films showed an abnormal ascites retention. Laboratory tests revealed positive CRP and increased ESR values. Again, it was suggested that she had not only a central nervous but also a peritoneal infection giving rise to ascites. From samples of ventricular CSF and ascites, cryptococcus neoformans was cultured. The lumbar CSF revealed positive latex agglutination titer for cryptococcal antigen, although the culture was negative. The ascites examination revealed an increase in cell counts (mostly lymphocytes) and protein content, and positive Rivalta and Runneberg reactions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Central nervous cryptococcosis giving rise to ascites after ventriculo-peritoneal shunting--a case report]. 322 72


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