Scopulariopsis brevicaulis is a common soil saprobic mould. Occasionally, S. brevicaulis has been reported as an etiologic agent of human disease. The spectrum of human mycoses includes toenail infection, hypersensitivity pneumonitis, fungus ball formation in a preformed pulmonary cavity, and, most recently, documented deep tissue infections in immunocompromised hosts. A case of invasive hyalohyphomycosis of the great toe caused by S. brevicaulis is reported in an allogeneic bone-marrow transplant recipient.

Adult↗

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Comparison of D0870 and fluconazole in the treatment of murine cryptococcal meningitis.

Cryptococcal meningitis is a common infection in patients with AIDS. Using a murine cryptococcosis model, we compared treatment with a new triazole, D0870, and fluconazole. Groups of ICR (Institute for Cancer Research) mice were infected intracerebrally with eight different isolates of Cryptococcus neoformans variety neoformans with different in vitro susceptibilities to fluconazole. For survival studies mice were challenged with two to four times LD(50) or six to nine times LD(50). Treatment was given for 10 days. Mice were observed through to day 30. To assess the effect of treatment on fungal tissue burden, mice received a three to five times LD(50) inoculum and treatment for 10 days. They were sacrificed on day 12 and serial dilutions of brain homogenates were cultured. Fluconazole prolonged survival primarily in isolates which were susceptible in vitro. D0870 prolonged survival in all isolates except one, which was also resistant in vitro to D0870 and fluconazole. Both drugs reduced colony counts of all isolates. D0870 warrants further development for use in cryptococcosis, and appears effective for isolates relatively resistant to fluconazole. There is a relative correlation of in vivo and in vitro susceptibility to D0870 as well as fluconazole.

Animals↗

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Problems in the diagnosis of invasive fungal diseases.

Invasive mycoses are escalating in frequency in contemporary medicine; most dramatic is the rise in the prevalence of opportunistic fungal infections among immunocompromised hosts. Despite increased awareness among physicians and greater mycologic acumen, morbidity and mortality remain substantial. In part, this situation is due to the difficulties encountered in the diagnosis of fungal infections by both the clinician and the laboratorian. Some of the factors contributing to these difficulties include the abrogation of the immune response associated with improved medical technology, the impact of AIDS, the invasion of the immunocompromised host by fungi previously considered to be saprobic, and the minimal mycologic training of medical personnel. Research efforts are under way that may be expected to improve the diagnosis and treatment of invasive mycotic diseases in the near future. For the present, it is recommended that mycologic training be encouraged and improved for all health care professionals.

Acquired Immunodeficiency Syndrome↗

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Invasive aspergillosis.

Invasive fungal disease of humans caused by species of the genus Aspergillus Micheli ex Linnaeus has become a significant and prevalent problem in contemporary medicine, particularly with regard to the compromised host. This review addresses the current status of invasive aspergillosis, including microbiological, clinical, and pathologic aspects. Diagnostic and therapeutic considerations are discussed with a view toward early and aggressive intervention in order to prevent the high mortality rate associated with aspergillosis.

Antifungal Agents↗

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Mycoses caused by Candida lusitaniae.

Candida lusitaniae, a fungus with a low incidence of infection in immunocompetent people, is emerging as an opportunistic pathogen in immunocompromised hosts. This yeast is generally resistant to amphotericin B and may present therapeutic difficulties. C. lusitaniae may be misidentified as one of several other fungal species, including Candida tropicalis, Candida parapsilosis, and even Saccharomyces cerevisiae. As judged by in vitro antifungal susceptibility testing, minimal inhibitory concentrations of antifungal agents other than amphotericin B are achievable, but fungicidal levels are not. When encountered in blood or other body sites, C. lusitaniae should be carefully considered as a potential pathogen.

Aged↗

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Determination of SCH 39304 by megabore capillary gas-liquid chromatography.

A gas-liquid chromatographic procedure for determination of SCH 39304 at low nanogram concentrations in serum, cerebrospinal fluid, and urine is presented. The methodology combines a high selectivity and sensitivity nitrogen-specific detector, a gas chromatograph equipped with a capillary "megabore" column, and an internal standard that is very similar in chemical structure to the drug being assayed. This method is suitable for both pharmacokinetic studies as well as for monitoring drug levels in patients receiving SCH 39304 for antifungal treatment.

Antifungal Agents↗

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The relationship of oral Candida tropicalis infection to systemic candidiasis in a patient with leukemia.

Oropharyngeal candidiasis is an extremely common complication in patients receiving chemotherapy for leukemia. Candida tropicalis appears to be the major infectious agent when these patients develop candidemia. In this article, a case of C tropicalis fungemia with oropharyngeal manifestations is presented. The relationship of oropharyngeal candidiasis to oral candidal infection is discussed.

Adult↗

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A comparison between fluconazole tablets and clotrimazole troches for the treatment of thrush in HIV infection.

Fluconazole, a newly available triazole, has been evaluated extensively as a treatment for thrush. It has been effective in the treatment of this condition in patients with HIV infection. Clotrimazole troches have been a common treatment for thrush in patients with HIV infection for several years. This study compared the efficacy and safety of fluconazole 100 mg tablets once per day versus clotrimazole 10 mg troches five times per day in the treatment of thrush in patients with HIV infection. Patients were evaluated at baseline, day 7, 14, 28, and 42. The following parameters were evaluated: clinical cure, colonization at the end of treatment, relapse at day 28, and relapse at day 42. Side effects including liver enzyme values were also monitored. Clinical cure was superior with fluconazole tablets than with clotrimazole troches. Also, rates of colonization at the end of therapy and relapse at days 28 and 42 were less with fluconazole tablets than with clotrimazole troches. However, these differences were not statistically significant. Patient compliance with fluconazole was superior to that of clotrimazole. This difference was statistically significant. Both fluconazole tablets and clotrimazole troches are effective in treating thrush in patients with HIV infection. The avoidance of multiple-per-day dosing would appear to favor fluconazole.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

The epidemiology of non-albicans Candida in oropharyngeal candidiasis in HIV patients.

Oropharyngeal candidiasis (OPC) is the most common fungal infection in patients with HIV infection. Fluconazole has been proven to be very effective in treating this infection, but decreased susceptibility of Candida to this drug has emerged. Certain non-albicans species such as C. glabrata and C. krusei are commonly less susceptible to fluconazole than C. albicans and are being isolated with increased frequency in HIV patients. The purpose of this study was to determine if the presence of non-albicans Candida with OPC in HIV patients had an impact on clinical presentation. This study shows that late-stage HIV patients have a high prevalence of Candida with decreased susceptibility to fluconazole, especially non-albicans species. OPC episodes with non-albicans isolates were more likely to require higher doses of fluconazole to achieve clinical cure. Also, the presence of non-albicans Candida was more frequently associated with severe symptoms.

AIDS-Related Opportunistic Infections↗

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Treatment of mycotic rhinitis with itraconazole in three horses.

Itraconazole, a third-generation azole, was evaluated for treatment of resistant nasal mycotic infections in horses. Two horses with Aspergillus spp nasal granulomas and 1 horse with Conidiobolus coronatus nasal infection were treated with itraconazole (3 mg/kg PO bid). One of the horses with nasal aspergillosis was also treated by surgical resection of the nasal septum. The treatment time for the horses ranged from 3 to 4.5 months. No adverse effects were noted in any of the horses during the treatment period. Peak and trough serum itraconazole concentrations were < 0.5 micrograms/mL in all 3 horses. Itraconazole (3 mg/kg PO bid) appears to be effective in the treatment of nasal Aspergillus spp infections in horses because the fungal infection was eliminated in both horses. One horse still had excessive nasal sounds during exercise and was retired from training, whereas the other horse returned to normal. The nasal C. coronatus infection appeared resistant to itraconazole treatment in the affected horse because the granulomas were still present after 4.5 months of treatment.

Animals↗

PubMedDate not supplied

Treatment of blastomycosis with itraconazole in 112 dogs.

One hundred twelve client-owned dogs with blastomycosis were treated with itraconazole, 5 or 10 mg/kg/d. The first group of 70 dogs treated in 1987 and 1988 received 10 mg/kg/d (group 1), and the second group of 42 dogs treated after October 1988 received 5 mg/kg/d (group 2). Even though the groups were treated at different times, the dogs were similar in age and gender distribution, number of sites involved, and percent and severity of pulmonary involvement. The proportion of dogs cured with a 60-day course of itraconazole was similar for both groups (53.6% versus 54.3%) and for a second historical control group treated with amphotericin B (57%); the recurrence rate was also similar, 20%, 21.4%, and 20%, respectively. Dogs treated with itraconazole had similar mortality rates (25.7% at 5 mg/kg/d; 25% at 10 mg/kg/day) to those treated with amphotericin B (23%). Seventeen of the 23 dogs that died (74%), did so during the first week of treatment; these early deaths were usually attributed to respiratory failure. The only site of infection that was significantly associated with failure (death or recurrence) was the brain. There was a marked difference in survival times between dogs without lung disease or with mild lung disease compared with dogs with moderate or severe lung disease. Serum itraconazole concentrations reached steady state by 14 days of treatment. Dogs receiving 5 mg/kg/d of itraconazole (group 2) had mean serum concentrations of 3.55 +/- 2.81 mg/mL (range, 0.67 to 10.8 micrograms/mL), whereas dogs receiving 10 micrograms/kg/d (group 1) had mean concentrations of 13.46 +/- 8.49 micrograms/mL (range, 1.8 to 28 micrograms/mL) (P < or = .001). There was no association between cure and serum itraconazole concentrations. Dogs in group 1 had significantly more adverse effects than dogs in group 2 (P = .046). Anorexia was the most common adverse effect, occurring in 14.9% of dogs in group 1. Only 8% of dogs in group 2 had adverse effects. Serum concentrations of itraconazole were positively correlated with serum alkaline phosphatase and alanine aminotransferase activities. Our findings indicate that itraconazole administered at a dose of 5 mg/kg/d is the drug of choice for blastomycosis in dogs.

Alanine Transaminase↗

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Parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS: experience with thirteen patients.

OBJECTIVE: Cryptococcus neoformans infections of the central nervous system affect up to ten percent of AIDS patients. Standard therapy with amphotericin B with or without 5-flucytosine has a high rate of failure, relapse, and toxicity. Fluconazole is a new triazole antifungal agent available in both oral and intravenous forms that has shown efficacy in the primary and maintenance treatment of cryptococcal meningitis in AIDS patients. In this open, noncomparative trial, we evaluated the safety and efficacy of intravenous fluconazole followed by oral fluconazole in the treatment of acute cryptococcal meningitis in AIDS patients. METHODS: Thirteen AIDS patients with acute cryptococcal meningitis, or relapse after successful primary therapy, received 400 mg of intravenous fluconazole daily for 12-16 days followed by oral fluconazole 400 mg/d for the duration of primary therapy. If cerebrospinal fluid (CSF) cultures converted to negative within 32 weeks of treatment, the fluconazole dose was decreased to 200 mg/d as maintenance therapy. RESULTS: Fluconazole therapy was successful in six patients (46 percent) and unsuccessful in seven (54 percent). Of the seven patients considered unsuccessful, one demonstrated clinical improvement but remained CSF-culture positive, five were clinical failure and were switched to amphotericin B therapy, and one died after two weeks secondary to cryptococcal meningitis. No patient experienced any adverse reactions necessitating discontinuation of therapy. CONCLUSIONS: In this small group of patients, moderate doses of parenteral and oral fluconazole for acute cryptococcal meningitis in AIDS patients demonstrated failure rates similar to those reported in other studies with fluconazole and with amphotericin B. As there was no difference in initial Karnofsky scores or the severity of disease in treatment successes versus failures, it is difficult to determine who might respond to fluconazole as initial therapy or who should be treated initially with another agent. Further studies and clinical experience are needed.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Itraconazole-didanosine excipient interaction.

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Adult↗

PubMedDate not supplied

Discrepancy between in vitro and in vivo antifungal activity of albendazole.

Albendazole has in vitro activity against Cryptococcus neoformans and reduced in vitro activity for albendazole when compared with Candida albicans. The major metabolite of albendazole, albendazole sulphoxide showed no in vitro activity against isolates of either fungus. Immunocompetent mice infected intravenously (i.v.) with C. albicans were treated with albendazole doses of 20-600 mg kg-1 per day in noble agar or sesame oil for per oral (PO) administration, or 80 mg kg-1 per day in DMSO for intraperitoneal (i.p.) and i.v. administration for 10 days, and were observed for survival. Mice infected with C. neoformans intracranially received albendazole in daily doses of 600 mg kg-1 prepared in DMSO (i.p.) or peanut butter/rat chow (PO) for 10 days and were observed for survival. Mortality was not different between the treated and control animals in any study. Plasma samples from uninfected mice dosed with similar formulations and doses of albendazole were analysed by HPLC for albendazole and albendazole sulphoxide. No albendazole could be detected in any sample, while concentrations of albendazole sulphoxide (286-8697 ng ml-1) were observed in all samples. These data suggest that the absence of in vivo activity for albendazole is due to rapid conversion to the inactive albendazole sulphoxide metabolite.

Albendazole↗