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At least 1,423 records · Page 79Linked to original sources
PubMed2001

Pharmacokinetic and pharmacodynamic modeling of anidulafungin (LY303366): reappraisal of its efficacy in neutropenic animal models of opportunistic mycoses using optimal plasma sampling.

The compartmental pharmacokinetics of anidulafungin (VER-002; formerly LY303366) in plasma were characterized with normal rabbits, and the relationships between drug concentrations and antifungal efficacy were assessed in clinically applicable infection models in persistently neutropenic animals. At intravenous dosages ranging from 0.1 to 20 mg/kg of body weight, anidulafungin demonstrated linear plasma pharmacokinetics that fitted best to a three-compartment open pharmacokinetic model. Following administration over 7 days, the mean (+/- standard error of the mean) peak plasma concentration (C(max)) increased from 0.46 +/- 0.02 microg/ml at 0.1 mg/kg to 63.02 +/- 2.93 microg/ml at 20 mg/kg, and the mean area under the concentration-time curve from 0 h to infinity (AUC(0-infinity)) rose from 0.71 +/- 0.04 to 208.80 +/- 24.21 microg. h/ml. The mean apparent volume of distribution at steady state (V(ss)) ranged from 0.953 +/- 0.05 to 1.636 +/- 0.22 liter/kg (nonsignificant [NS]), and clearance ranged from 0.107 +/- 0.01 to 0.149 +/- 0.00 liter/kg/h (NS). Except for a significant prolongation of the terminal half-life and a trend toward an increased V(ss) at the higher end of the dosage range after multiple doses, no significant differences in pharmacokinetic parameters were noted in comparison to single-dose administration. Concentrations in tissue at trough after multiple dosing (0.1 to 10 mg/kg/day) were highest in lung and liver (0.85 +/- 0.16 to 32.64 +/- 2.03 and 0.32 +/- 0.05 to 43.76 +/- 1.62 microg/g, respectively), followed by spleen and kidney (0.24 +/- 0.65 to 21.74 +/- 1.86 and <0.20 to 16.92 +/- 0.56, respectively). Measurable concentrations in brain tissue were found at dosages of > or =0.5 mg/kg (0.24 +/- 0.02 to 3.90 +/- 0.25). Implementation of optimal plasma sampling in persistently neutropenic rabbit infection models of disseminated candidiasis and pulmonary aspergillosis based on the Bayesian approach and model parameters from normal animals as priors revealed a significantly slower clearance (P < 0.05 for all dosage groups) with a trend toward higher AUC(0-24) values, higher plasma concentrations at the end of the dosing interval, and a smaller volume of distribution (P < 0.05 to 0.193 for the various comparisons among dosage groups). Pharmacodynamic modeling using the residual fungal tissue burden in the main target sites as the primary endpoint and C(max), AUC(0-24), time during the dosing interval of 24 h with plasma drug concentration equaling or exceeding the MIC or the minimum fungicidal concentration for the isolate, and tissue concentrations as pharmacodynamic parameters showed predictable pharmacokinetic-pharmacodynamic relationships in experimental disseminated candidiasis that fitted well with an inhibitory sigmoid maximum effect pharmacodynamic model (r(2), 0.492 to 0.819). However, no concentration-effect relationships were observed in experimental pulmonary aspergillosis using the residual fungal burden in lung tissue and survival as parameters of antifungal efficacy. Implementation of optimal plasma sampling in discriminative animal models of invasive fungal infections and pharmacodynamic modeling is a novel approach that holds promise of improving and accelerating our understanding of the action of antifungal compounds in vivo.

Anidulafungin↗
PubMed1995

Endemic mycoses in AIDS: a clinical review.

Histoplasmosis and coccidioidomycosis are serious opportunistic infections in patients with AIDS who reside in areas of endemicity of the United States and Central and South America. Blastomycosis, although less common, also must be recognized as an opportunistic infection in patients with AIDS. Prompt diagnosis requires knowledge of the clinical syndromes and diagnostic tests as well as a high index of suspicion. Histoplasmosis and blastomycosis respond well to antifungal treatment, but relapse is common without chronic suppressive therapy. Improvements in treatment are needed in coccidioidomycosis. Research is needed to identify preventive strategies for patients at risk. These strategies may include use of prophylactic antifungal therapy or vaccination.

AIDS-Related Opportunistic Infections↗
PubMed1982

Gluteal abscess caused by Phialophora hoffmannii and review of the role of this organism in human mycoses.

Infections caused by members of the Phialophora hoffmannii (Beyma) Schol-Schwarz fungal aggregate (a group of related taxa, especially species of uncertain circumscription) are not reported frequently. This case report concerns the development of a gluteal abscess after multiple intramuscular injections of antimicrobial agents. Microbiological examination of the abscess material yielded a pure growth of the mold P. hoffmannii. Hyphal elements in the purulent exudate were only demonstrated when the specimen was digested by an N-acetyl cysteine-NaOH digestion-decontamination procedure or in stained paraffin block sections of the exudate. Other cases of disease caused by members of this fungal aggregate and the status of the mycology of this organism are reviewed.

Abscess↗
PubMed1998

Detection of antigen in sera of patients with invasive aspergillosis: intra- and interlaboratory reproducibility. The Dutch Interuniversity Working Party for Invasive Mycoses.

The intra- and interlaboratory reproducibilities of a commercial sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of Aspergillus galactomannan in serum (Platelia Aspergillus; Sanofi Diagnostics Pasteur, Marnes-La-Coquette, France) were evaluated in six laboratories of university hospitals. Twenty serum samples were obtained from 12 neutropenic patients including 6 with invasive aspergillosis. These samples were blinded and sent to each center together with eight blinded ELISA-negative serum samples spiked with known concentrations of galactomannan. The centers were provided with ELISA microtiter plates from a single batch and a detailed protocol. Ten clinical samples showed ELISA reactivity, while 10 samples were ELISA negative. The mean coefficient of variation (CV) of the optical density values was 4.24% within a single assay and 25.6% between runs. The interassay CV of the ratios for the serum samples tested was 18.6%. Analysis of ordinal interpretation of the ELISA result (i.e., negative, gray zone, or positive) showed excellent reproducibility. Recalculation of the cutoff values for positive and negative samples suggested that the cutoff level recommended by the manufacturer could be lowered from 1.0 to 0.8 for negative samples and from 1.5 to 1.0 for positive samples. The intra- and interlaboratory reproducibilities were excellent when the ELISA results were interpreted as ordinal data, but considerable variation in optical density values and, to a lesser extent, in the ratios for the serum samples tested, was observed between runs. High assay variability was also found for serum samples spiked with known concentrations of galactomannan. Therefore, antigen titers in serum samples from a single patient, measured in different runs, should be compared with caution.

Antigens, Fungal↗
PubMed2005

Development of a DNA microarray for detection and identification of fungal pathogens involved in invasive mycoses.

Invasive fungal infections have emerged as a major cause of morbidity and mortality in immunocompromised patients. Conventional identification of pathogenic fungi in clinical microbiology laboratories is time-consuming and, therefore, often imperfect for the early initiation of an adequate antifungal therapy. We developed a diagnostic microarray for the rapid and simultaneous identification of the 12 most common pathogenic Candida and Aspergillus species. Oligonucleotide probes were designed by exploiting the sequence variations of the internal transcribed spacer (ITS) regions of the rRNA gene cassette to identify Candida albicans, Candida dubliniensis, Candida krusei, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida guilliermondii, Candida lusitaniae, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, and Aspergillus terreus. By using universal fungal primers (ITS 1 and ITS 4) directed toward conserved regions of the 18S and 28S rRNA genes, respectively, the fungal ITS target regions could be simultaneously amplified and fluorescently labeled. To establish the system, 12 pre-characterized fungal strains were analyzed; and the method was validated by using 21 clinical isolates as blinded samples. As the microarray was able to detect and clearly identify the fungal pathogens within 4 h after DNA extraction, this system offers an interesting potential for clinical microbiology laboratories.

Aspergillosis↗
PubMed1995

Thoracic mycoses from endemic fungi: radiologic-pathologic correlation.

The endemic fungi Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis are primary human pathogens whose major portal of entry is the respiratory tract. Their clinical manifestations are categorized as acute, chronic or chronic progressive, or disseminated fungal disease. Most acute pulmonary infections are self-limited, and many are asymptomatic. Chronic, progressive, or disseminated disease is much less common and most often occurs in immunocompromised patients. The radiologic manifestations of these disorders are protean. They include interstitial or air-space opacities, solitary or multiple pulmonary nodules, parenchymal masses, cavities, and hilar or mediastinal adenopathy. The diagnosis of a thoracic mycosis requires familiarity with the epidemiology of the fungus in question, the various modes of clinical presentation, and the full spectrum of radiologic manifestations. Although skin and serologic tests can be useful, definitive diagnosis requires culture of the fungus from infected tissue or demonstration of the organism at microscopic examination.

AIDS-Related Opportunistic Infections↗
PubMed1982

Epidemiology and the prevention of peripartal mycoses.

About 30% of all pregnant women are affected by antepartal vaginal yeast contamination. During the past 40 years this incidence has remained unchanged throughout the world. Due to the close contact of the baby with the contaminated area during parturition, yeasts are transmitted to the skin surface of the newborn. Yeasts are still demonstrable in more than 10% of all newborn on the 5th day of life. All newborn presenting yeast contamination on the 7th day of life are likely to develop a clinically manifest thrush by the end of the 2nd week of life. If the yeast contamination is acquired at a later stage, the risk of infection is much lower. Extensive mycological examinations of the newborn nursing staff and of the environment of newborn have not indicated any causal relationship to contamination. The yeast reservoir of the maternal vagina may therefore, in the majority of cases, be regarded as the cause of perinatal thrush which affects about 13% of all newborn by the 4th week of life. A prophylaxis of neonatal thrush should thus be carried out before parturition. Both the incidence of vaginal and neonatal yeast contamination can be reduced by more than 60% by a general mycological examination of all pregnant women between the 34th and 36th week of pregnancy and treatment of a possible yeast contamination with a local antifungal.

Candidiasis, Oral↗
PubMed1980

Follow-up study after more than one year including 100 patients treated for superficial mycoses.

A total of 100 patients with dermatomycoses were treated with econazole nitrate 1% or with the same compound combined with triamcinolone acetonide 0.1%. The patients were supposed to undergo clinical and mycological follow-up examinations at an average of 15 months after cure had been obtained. Of the 100 patients, 83 were followed up: 78 (95%) reported neither relapses nor reinfections; 4 (5%) presented with clinical symptoms and positive mycological examination and in 1 patient the mycological examination was positive but no clinical symptoms were present. Generally speaking, the results can be considered excellent.

Adolescent↗
PubMed1989

A double-blind clinical trial of fenticonazole (2%) spray versus naftifine (1%) spray in patients with cutaneous mycoses.

A multi-centre, double-blind trial was carried out in 100 patients with cutaneous mycotic infections, confirmed by direct microscopy and/or culture, to compare the efficacy and tolerability of spray formulations of 2% fenticonazole and 1% naftifine. On entry, patients were allocated at random to receive once daily topical applications of one or other drug over a period of 2 to 4 weeks, treatment being stopped when patients had recovered or substantially improved. Clinical and mycological assessments were made before (baseline), at weekly intervals during treatment and, if possible, 2 to 3 weeks after the end of treatment (drug-free period). Treatment was continued for 19.25 days with fenticonazole and 19.62 days with naftifine. All patients had positive mycological findings on entry. The most frequently isolated pathogens were dermatophytes, mainly Trichophyton rubrum; however, Candida albicans was present in 33.3% of patients in the fenticonazole group and in 20.8% of those treated with naftifine. At the end of treatment, only 3 (6.3%) and 5 (10.4%) patients, respectively, of the 48 patients assessed in each group still had positive mycological findings. Assessments of symptoms indicated comparable, significant improvement in both groups, and at the end of treatment the overall opinion of doctors and patients was that about 90% of patients were cured or greatly improved. The end of the drug-free period evaluation showed that, of the patients assessed as cured or greatly improved at the end of treatment, only 1 (3.2%) patient who had received fenticonazole and 2 (6.3%) who had received naftifine were confirmed mycologically as having relapsed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1992

Disseminated mycoses in cattle. A study on nine autopsy cases.

Nine cases affected with disseminated mucormycosis (1.3% of all autopsy cases and 20.0% of systemic mycosis) were found among bovine systemic mycosis examined from 1975 to 1985. The disseminated lesions were found in the lungs (3 cattle), heart (2 cattle), liver (2 cattle), spleen (1 beef cattle), kidneys (1 cattle), central nervous system (1 cattle) and lymph node (1 cattle). Histological examination revealed granulomatous lesions, necrotic foci including infarcts, and thromboangiitis with the hyphae of a member of the Zygomycetes and neutrophil reaction. Granulomatous lesions with asteroid bodies were found in the liver. Metastatic foci were established from the primary lesions found in the alimentary organ (4 from the forestomach or abomasum and 1 from the tongue). One case resulted from uterine mucormycosis, and no primary lesion was found in the other 3 cattle. Complicated infection with respiratory aspergillosis occurred in 4 cases with alimentary mucormycosis. All of the 9 cattle had predisposing disorders. Six cattle had been manifested with prolonged debilitating conditions. Anemia was present in 4, leukopenia in 2 and lymphopenia in 1 cattle.

Animals↗