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 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A retrospective review of therapeutic failures of miconazole in three patients is presented. Miconazole, a new imidazole derivative, is a broad-spectrum antifungal agent purportedly effective topically, orally, and parenterally against a number of species of fungi. Three patients with the following culturally proven deep fungal infections were treated with miconazole: (i) destructive arthritis (Sporothrix schenckii), (ii) meningoencephalitis (Cryptococcus neoformans), and (iii) disseminated aspergillosis (Aspergillus fumigatus). All the organisms were susceptible in vitro to 1.56 mug or less of miconazole per ml using a broth dilution technique. In each patient, miconazole administered intravenously in dosages of 30 mg/kg per day failed to control or eradicate infection. Miconazole serum levels ranged from <0.5 to 4.35 mug/ml as determined by radial diffusion bioassay. Cerebrospinal fluid levels were virtually undetectable. In one patient (C. neoformans), miconazole was given intraventricularly in doses of 15 mg without response. Therapeutic failures were attributed to suboptimal body fluid levels of miconazole. The reason(s) for such low levels of activity was not clear, but may have been poor penetrance into tissues, in vitro inactivation, and/or unusually rapid excretion. Untoward reactions from miconazole included fever, chills, nausea, vomiting, and phlebitis.
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PMID:Therapeutic failures with miconazole. 35 23

This paper presents a case of successful treatment of candida meningitis with miconazole. A 55-year-old woman was admitted due to high fever, vomiting and urinary incontinence on November 11, 1986. Four months prior to this episode, she had been treated for a ruptured aneurysm with neck-clipping and V-P shunt for NPH. Candida albicans was cultured from her CSF. The shunt system was immediately removed and an Ommaya's reservoir was installed for external drainage and intrathecal administrations. Combination therapy (amphotericin B and flucytosine) was initiated. However, it was discontinued after ten days because of high fever and chills after intrathecal injection of amphotericin B. Treatment with miconazole intrathecally (10-90 mg/week, total 565 mg) and intravenously (200-1200 mg/day, total 70.4 g) was begun on November 23. Clinical and CSF findings were improved soon. No side effect of miconazole was observed. After V-P shunt revision, she was discharged without neurological deficit on March 12, 1987. Reports of mycosis in central nervous system are recently increasing, especially for candidosis. Cryptococcosis is noted frequently as an opportunistic infection of AIDS. The administration of amphotericin B and flucytosine has been the main therapy for mycotic meningitis. Unfortunately, however, Amphotericin B has many toxic effects, including renal dysfunction, and flucytosine can induce the emergent resistance. Miconazole has been used to successfully treat cryptococcosis, aspergillosis or coccidiosis, and was effective in our case of candida meningitis. Few side effects have been reported with its use. The intrathecal injection of miconazole is recommended for meningitis, because the drug is taken up minimally into CSF space after intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Successful treatment of Candida meningitis with miconazole]. 224 81

Laboratory and clinical study was carried out on miconazole (MCZ), a new synthetic imidazole. The antifungal activity of MCZ was studied and expressed as MICs for clinical isolates. The drug proved to have the highest activity against Cryptococcus neoformans, with MICs of no more than 0.16 micrograms/ml for all isolates of this species. MICs of Torulopsis glabrata were 0.08-5 micrograms/ml for all isolates and those of Candida albicans and Candida tropicalis were 5-20 micrograms/ml for more than 90% of the isolates. Most of other strains were less than 10 micrograms/ml. When 3 healthy adult men were administered each with 200 mg of MCZ by intravenous drip infusion for 1.25 hours, the mean serum MCZ concentration was 1.39 micrograms/ml at the end of the infusion, then decreased rapidly to 0.49 microgram/ml in following 30 minutes, and then decreased gradually to 0.17 microgram/ml 6 hours later. The mean cumulative urinary excretion rate of the drug was as low as 3.0% at this stage. A total of 25 patients with ages of 30-78 years, comprising 17 men and 8 women, were treated with 200-1,800 mg of MCZ daily for 3-93 days. The clinical effectiveness was ascertained in 19 cases among the patients; 9 cases with candidiasis, 3 with cryptococcosis and 7 with aspergillosis. Clinical responses were excellent in 2, good in 9 and poor in 8 cases, and its efficacy rates was 58%. The efficacy rate of the combination therapy with other antifungal agents was 60% in comparison with 57% of MCZ alone. Adverse reactions to the drug such as nausea, vomiting and anorexia were observed in 3 cases (12%). Abnormal changes in laboratory parameters were also observed: 3 patients with elevations of GOT and GPT, and another with eosinophilia.
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PMID:[Laboratory and clinical study of intravenous miconazole]. 359 80

A 4-year-old female German Shepherd Dog was examined to determine the cause of ataxia, progressive head tilt, anorexia, lethargy, and weight loss of 3 weeks' duration. A vestibular syndrome, generalized lymphadenopathy, bilateral uveitis, and chorioretinitis with complete detachment of the left retina were detected. Abnormal clinicopathologic findings were isosthenuria and hyperglobulinemia. The non-functional left eye was enucleated and fungal organisms resembling Aspergillus spp were identified on histologic examination. Microbial culture of a urine sample yielded Acremonium sp, which was initially considered a contaminant. The dog was considered to have systemic aspergillosis and was treated with itraconazole for 7 months, until it was euthanatized because of persistent vomiting and anorexia. Postmortem examination revealed multisystemic pyogranulomatous and necrotizing inflammation of the myocardium, pericardium, liver, and kidneys; and granulomatous splenitis, lymphadenitis, retinitis, endometritis, and meningoencephalitis. Fungal culture of affected organs yielded Acremonium sp. These findings indicated that Acremonium spp can be pathogenic and should not be ignored when cultured.
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PMID:Systemic mycosis caused by Acremonium sp in a dog. 825 22

Caspofungin is the first in a new class of antifungal agents, the glucan synthesis inhibitors, that interfere with fungal cell wall synthesis. Caspofungin exhibited in vitro and in vivo efficacy against a wide range of fungi and yeasts including Aspergillus and Candida species. A complete or partial response to caspofungin therapy was seen in 40.7% of immunocompromised adults with invasive aspergillosis who did not respond to, or did not tolerate, other antifungal agents in a noncomparative multicentre study. Caspofungin was effective in patients with oropharyngeal or oesophageal candidiasis, according to the preliminary results of 2 randomised double-blind trials. Caspofungin was generally well tolerated in a multicentre noncomparative trial involving patients with invasive aspergillosis. One or more drug-related clinical adverse effects were experienced by 13.8% of caspofungin recipients (the most common were fever, nausea, vomiting and complications associated with the vein into which caspofungin was infused). The tolerability of caspofungin appeared to be better than that of amphotericin B and similar to that of fluconazole in double-blind, randomised trials involving patients with mucosal candidiasis.
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PMID:Caspofungin. 1146 73

A 74-year-old man with diabetes mellitus type II, retinopathy and polyneuropathy suffered from exophthalmus, ptosis and diplopia. Magnetic resonance imaging and computer tomography showed a space-occupying process in the right orbital apex. An extranasal ethmoidectomy accompanied by an orbitotomia revealed the presence of septated hyphae. Aspergillus fumigatus was grown from the tissue. After surgical removal of the fungal masses, therapy with amphotericin B (1 mg kg(-1) body weight) plus itraconazole (Sempera, 200 mg per day) over 6 weeks was initiated. Five months later the patient's condition deteriorated again, with vomiting, nausea and pain behind the right eye plus increasing exophthalmus. Antifungal therapy was started again with amphotericin B and 5-fluorocytosine. Neutropenia did not occur. The patient became somnolent and deteriorated, a meningitis was suggested. Aspergillus antigen (titre 1:2, Pastorex) was detected in liquor. Anti-Aspergillus antibodies were not detectable. Both the right eye and retrobulbar fungal masses were eradicated by means of an exenteratio bulbi et orbitae. However, renal insufficiency and an apallic syndrome developed and the patient died. At autopsy, a mycotic aneurysm of the arteria carotis interna dextra was detected. The mycotic vasculitis of this aneurysm had caused a rupture of the blood vessel followed by a massive subarachnoidal haemorrhage. In addition, severe mycotic sphenoidal sinusitis and aspergillosis of the right orbit were seen, which had led to a bifrontal meningitis.
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PMID:Case report. Mycotic arteritis due to Aspergillus fumigatus in a diabetic with retrobulbar aspergillosis and mycotic meningitis. 1176 8

OBJECTIVES: To evaluate the efficacy of low dose fluconazole treatment for the prevention of yeast colonization and infection in severely neutropenic patients. METHODS: An open randomized trial, comparing fluconazole (100 mg per day) with nystatin (800,000 IU per day), in a University Hospital setting. RESULTS: Antifungal prophylaxis was given during the period of neutropenia, defined as less than 500 polymorphonuclear cells (PMN)/mm3). Thirty-six patients were randomly assigned to fluconazole and 33 to nystatin treatment groups. New oropharyngeal colonizations were significantly reduced by fluconazole (P=0.005), and oropharyngeal infections occurred less frequently in the fluconazole group (3% versus 16%, P=0.07). Stool colonization was identical between both groups. Systemic fungal infections were rare; one fluconazole patient had pulmonary aspergillosis and one nystatin patient developped Candida pseudotropicalis fungemia. Empiric amphotericin B was given with the same frequency in both groups. No side effects were associated with fluconazole. However, the administration of nystatin became impossible for three patients because of vomiting and lack of compliance. CONCLUSIONS: Fluconazole (100 mg per day) is more effective than nystatin for the prevention of oropharyngeal yeast colonization. Comparison with results in the literature suggests that a 100-mg dose of fluconazole has similar effects to 200 or 400 mg per day.
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PMID:Antifungal Prophylaxis in Severely Neutropenic Patients: How Much Fluconazole is Necessary? 1186 17

Anidulafungin is a novel antifungal agent which, like other echinocandins, inhibits beta-(1,3)-D-glucan synthase and disrupts fungal cell-wall synthesis. It has marked antifungal activity against a broad spectrum of Candida spp. and Aspergillus spp., including amphotericin B- and triazole-resistant strains. In clinical trials, anidulafungin has primarily been evaluated in patients with oesophageal and invasive candidiasis. Preliminary data are emerging for other indications such as invasive aspergillosis. In a large, multicentre, double-blind, double-dummy, randomised trial in patients with oesophageal candidiasis, intravenous anidulafungin 50 mg/day was as effective as oral fluconazole 100 mg/day regarding end-of-treatment rates of endoscopic cure and clinical and microbiological success. Duration of treatment was approximately 2-3 weeks, and patients in both groups received a loading dose of study drug (twice the daily maintenance dose) on day 1. Anidulafungin is generally well tolerated. Across the dosage range 50-100 mg/day, adverse events appear not to be dose- or infusion-related. In the largest clinical trial to date, the most common treatment-related adverse events were phlebitis/thrombophlebitis, headache, nausea, vomiting and pyrexia.
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PMID:Anidulafungin. 1545 42

We conducted a multicenter postmarketing study to investigate the efficacy and safety of reinduction therapy with a high-dose cytarabine-containing regimen for pediatric patients with relapsed or refractory acute leukemia. Seven of 13 patients (53.8%) with ALL achieved complete or partial remission, and only 1 of 6 patients (16.7%) with AML achieved partial remission. The frequent non-hematologic adverse events were gastrointestinal toxicities, such as vomiting, diarrhea and abdominal pain, as well as pyrexia and headache. Infection appeared in 9 of 20 (45%) patients. There were two death during reinduction therapy. One died of invasive bronchopulmonary aspergillosis, and the other died of intracranial hemorrhage and renal failure. These results indicated that a high-dose cytarabine regimen is effective as reinduction therapy in pediatric patients with relapsed ALL, and supportive care is essential to prevent or control treatment-related adverse events, such as infection.
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PMID:[Effectiveness of remission induction with high-dose cytarabine for relapsed or refractory pediatric acute leukemia]. 2037 1

Antifungal prophylaxis during treatment for haematological malignancies has been studied for 50 years, yet it has not been wholly effective even when using antifungal drugs that exhibit potent activity in vitro against a broad range of fungal pathogens. Trials have demonstrated that it can reduce the incidence of invasive fungal diseases (IFD) and fungal deaths, but only two studies have had an impact on overall mortality. Furthermore, it has not significantly reduced the need for empirical antifungal therapy. Posaconazole was effective in preventing invasive aspergillosis in two studies of high-risk patients, and consensus guidelines grade it as a suitable choice for antifungal prophylaxis of invasive mould disease; however, its bioavailability was compromised by vomiting or diarrhoea so that an alternative parenteral antifungal drug was required. A recent trial of voriconazole prophylaxis after allogeneic stem cell transplantation failed to show superiority over fluconazole. With more accurate definitions of IFD, that utilize fungal biomarkers, such as galactomannan, together with computerized tomographic imaging, there is growing interest in a diagnostic-driven strategy, which could prove to be a more efficacious approach.
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PMID:Antifungal prophylaxis during treatment for haematological malignancies: are we there yet? 2150 22


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