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F C Odds

Publications and source records attributed to F C Odds.

At least 73 records · Page 4Linked to original sources

Intraconazole--a new oral antifungal agent with a very broad spectrum of activity in superficial and systemic mycoses.

Itraconazole is a triazole-derivative antifungal agent with an extremely broad spectrum of action in vitro, in experimental animals in vivo and in clinical trials. When taken orally, itraconazole achieves high and sustained levels of active drug in many tissues, including skin, nail and most deep organs. Its clinical value has been proved in all forms of mycosis affecting the skin and mucous membranes and in onychomycosis. In systemic infections, clinical trials have led to recommendations that itraconazole is the current drug of choice for blastomycosis, histoplasmosis, paracoccidioidomycosis, lymphocutaneous sporotrichosis, chronic disseminated aspergillosis and many cases of phaeohyphomycosis. It is also finding application in deep-seated Candida infections and in cryptococcosis. Its safety profile is extremely good, with very few non-trivial adverse experiences noted in a large series of patients treated and monitored. Itraconazole therefore represents a useful therapeutic advance for the management of most forms of fungal infection.

Administration, Oral↗

Resistance of yeasts to azole-derivative antifungals.

There are relatively few antifungal agents available for the treatment of systemic mycoses. The incidence of these infections, particularly among the immunocompromised, has increased significantly in recent years. Amphotericin B, flucytosine and the azole-derivatives--fluconazole, itraconazole and ketoconazole--are the only drugs of value in the treatment of systemic yeast infections currently available. To date resistance among individual yeast species or strains has only been a serious problem with flucytosine. However, resistance among Candida spp. to orally administered azole-derivatives has been observed. The frequency with which resistance has been described in clinical practice among yeasts differs considerably between the three azole antifungal agents. Fluconazole has been implicated in emergent resistance more frequently than ketoconazole, and ketoconazole more often than itraconazole. It must be a matter for concern that, by analogy with the known emergence of antibiotic-resistance among bacteria, that the widespread use of a drug inactive against a particular species may lead to an increased incidence of such infections. An international epidemiological survey is required to establish the extent and degree of resistance to the azole antifungals.

Antifungal Agents↗

Effects of temperature on anti-Candida activities of antifungal antibiotics.

The relative growth (percentage of growth relative to control growth) of 767 Candida isolates representing five species was measured in microcultures at 25 and 37 degrees C. In the presence of 10(-4) M flucytosine, the distribution of relative yeast growth data indicated that Candida albicans isolates were less susceptible at 25 degrees C than at 37 degrees C, while the opposite was found with 4 x 10(-5) M amorolfine for most of the isolates tested. Repetition of the experiments at four different temperatures with 99 C. albicans isolates and five antifungal agents confirmed a direct relationship between growth inhibition and increasing temperature from 25 to 40 degrees C with amphotericin B, flucytosine, and terconazole; a strong inverse relationship between inhibition and temperature with amorolfine; and a weak inverse relationship with terbinafine. However, these relationships were not always noted with other Candida spp.: in particular, the growth of C. glabrata and C. parapsilosis isolates tended to be greater at 37 degrees C than at 25 degrees C in the presence of the azole-derivative antifungal agents itraconazole and terconazole. These findings stress the species-specific individuality of yeast susceptibility to azole antifungal agents. The results with C. albicans and amorolfine and terbinafine accord with their known in vivo efficacy in mycoses involving low-temperature superficial sites and poor activity against mycoses involving deep body sites. The data also reinforce the need for control of experimental variables such as temperature in the design of standardized yeast susceptibility tests.

Antifungal Agents↗

Nomenclature of fungal diseases: a report and recommendations from a Sub-Committee of the International Society for Human and Animal Mycology (ISHAM).

The ISHAM Mycoses Nomenclature Committee has considered the present status of fungal disease names. It suggests that the traditional approach to mycoses nomenclature in which the name of a causative taxon is suffixed with '-asis', '-iasis', '-osis' or '-mycosis' leads to names that are frequently unstable with respect to subsequent taxonomic and clinico-epidemiological changes. It is therefore recommended that individual mycoses should be named as often as possible in the form 'pathology A due to/caused by fungus X' or '[adjectival] fungus X pathology A' in preference to construction of names based solely on fungal taxa. A list of recommended mycosis names retained for their long tradition or intrinsic convenience is provided, together with a combined index and list of rejected names.

Animals↗

Effects of itraconazole on phagocytosis and killing of Candida glabrata by polymorphonuclear leucocytes from guinea pigs.

Itraconazole, a systemically active antifungal, was tested for its effects on microscopically assessed phagocytosis and killing of Candida glabrata 233 in vitro. Yeast cells were exposed to itraconazole in culture and guinea-pig peritoneal polymorphonuclear leucocytes were exposed to the drug injected intraperitoneally in vivo. At a concentration of 10(-7) M and with exposure times of 1 h, itraconazole pre-treatment of the leucocytes had no effect on the ability of PMNL to ingest or kill C. glabrata. However, pre-treatment of the growing C. glabrata cells under the same conditions significantly increased their vulnerability to both phagocytosis and intracellular killing. Longer exposures of the yeasts to itraconazole further increased their susceptibility to leucocyte phagocytosis, and it also rendered the cells vulnerable to killing merely by immersion in sodium deoxycholate solution. These findings indicate that short exposures of C. glabrata to low itraconazole concentrations damages the cells sublethally and renders them highly susceptible to leucocyte killing. Itraconazole had no direct effects on leucocyte function itself.

Animals↗

Expansion of the Candida albicans cell envelope in different morphological forms of the fungus.

Modes of cell envelope expansion were monitored in developing cells of Candida albicans 73/055 to which polystyrene beads were attached. Eight different conditions of culture medium, pH and temperature were used to promote growth in a variety of morphological forms. The cells were observed microscopically during growth in Sykes-Moore perfusion chambers, and sequential measurements of distances between the bead and the parent cell, and the bead and the apical tip were used to distinguish apical envelope expansion from general envelope expansion. Morphology index (Mi) was determined at each time point as an estimate of each cell's morphology. Calculations based on the measurements showed that general envelope expansion was inversely proportional to Mi, but that general expansion greater than 20% occurred only in cells with a final Mi less than 2.0, indicating that regulation of apical and general envelope expansion alone may be insufficient to determine the different morphologies seen in cells with higher Mi. The rate of expansion of the perimeter of cells was linearly proportional to the final Mi. This observation suggests that commitment to morphological development in C. albicans may in part involve commitment to a rate of envelope expansion, which itself helps determine the final morphology of a cell.

Candida albicans↗

Characterization of an azole-resistant Candida glabrata isolate.

A Candida (Torulopsis) glabrata strain (B57149) became resistant to fluconazole after a patient carrying the organism was treated with the drug at 400 mg once daily for 9 days. Growth of the pretreatment isolate (B57148) was inhibited by 50% with 0.67 microM ketoconazole, 1.0 microM itraconazole, and 43 microM fluconazole, whereas growth of B57149 was inhibited slightly by 10 microM ketoconazole but was unaffected by 10 microM itraconazole or 100 microM fluconazole. This indicates cross-resistance to all three azole antifungal agents. The cellular fluconazole content of B57149 was from 1.5- to 3-fold lower than that of B57148, suggesting a difference in drug uptake between the strains. However, this difference was smaller than the measured difference in susceptibility and, therefore, cannot fully explain the fluconazole resistance of B57149. Moreover, the intracellular contents of ketoconazole and itraconazole differed by less than twofold between the strains, so that uptake differences did not account for the azole cross-resistance of B57149. The microsomal cytochrome P-450 content of B57149 was about twice that of B57148, a difference quantitatively similar to the increased subcellular ergosterol synthesis from mevalonate or lanosterol. These results indicate that the level of P-450-dependent 14 alpha-demethylation of lanosterol is higher in B57149. Increased ergosterol synthesis was also seen in intact B57149 cells, and this coincided with a decreased susceptibility of B57149 toward all three azoles and amphotericin B. B57149 also had higher squalene epoxidase activity, and thus, more terbinafine was needed to inhibit the synthesis of 2,3-oxidosqualene from squalene. P-450 content and ergosterol synthesis both decreased when isolate B57149 was subcultured repeatedly on drug-free medium. This repeated subculture also fully restored the strain's itraconazole susceptibility, but only partly increased its susceptibility to fluconazole. The results suggest that both lower fluconazole uptake and increased P-450-dependent ergosterol synthesis are involved in the mechanism of fluconazole resistance but that only the increased ergosterol synthesis contributes to itraconazole cross-resistance.

Antifungal Agents↗

Antifungal susceptibility testing of Candida spp. by relative growth measurement at single concentrations of antifungal agents.

The relative growth (percentage of growth relative to control growth) of 496 isolates representing six Candida species was assessed as a means of determining in vitro susceptibilities of the isolates in microdilution plate wells containing single concentrations of each of seven antifungal agents. The relative growth data were highly reproducible. With flucytosine and amorolfine they correlated well with MICs, but for an azole antifungal agent, terconazole, they did not correlate with MICs. Distributions of relative growth percentages for different Candida spp. showed significant differences in species susceptibility to individual agents. For example, C. albicans was less susceptible than the other species to amorolfine; C. parapsilosis isolates were particularly susceptible to terbinafine; and C. glabrata, C. guilliermondii, and C. krusei isolates were less susceptible than C. albicans to fluconazole and ketoconazole but equally susceptible as or more susceptible than C. albicans to itraconazole. Differential patterns of susceptibility to individual azole antifungal agents were noted for some individual strains as well as for Candida spp.

Antifungal Agents↗

Genetic similarity and maintenance of Candida albicans strains from a group of AIDS patients, demonstrated by DNA fingerprinting.

By using the computer-assisted Dendron system to analyze the patterns of Southern blots probed with the repetitive sequence Ca3, we have compared oral isolates of Candida spp. from a group of 11 nonhospitalized patients with AIDS suffering from recurrent episodes of oral thrush in Leicester, England, with oral isolates from a group of control individuals. Genetic diversity among the AIDS strains was significantly reduced compared with that of control strains. In addition, the same strains persisted through recurrent infections in patients with AIDS. Although AIDS strains were genetically less diverse than either control strains or oral commensal strains analyzed in previous studies, the majority did not form a genetically distinct group. The results of this study suggest that in the majority of patients with AIDS in this group from Leicester, original commensal strains were replaced, replacement occurred early in the manifestation of AIDS, and replacement occurred only once.

Acquired Immunodeficiency Syndrome↗

Candida strains from neonates in a special care baby unit.

Carriage and acquisition of Candida spp and Candida albicans biotypes were studied among 163 neonates and 90 staff in a neonatal intensive care and surgical unit during a 17 week period. Twenty one neonates carried yeasts in the mouth, rectum or groin when first sampled, and a further 25 were positive later. C albicans accounted for 94.7% of 431 yeast isolates from neonates but only 67.4% of 43 isolates from staff. The first isolated C albicans biotype persisted in 13 babies monitored longitudinally. Simultaneous colonisation with two Candida spp was found in 2/46 neonates and 5/33 staff. The prevalence of candida was significantly higher among babies of gestational age less than 28 weeks (65%) than those of higher gestational age (26%). Oral and/or crural candida infection was observed in 14 of the babies but none developed deep seated candidosis. Routine antifungal prophylaxis did not affect the frequency of yeasts among the neonates.

Adult↗

Quantification of Candida albicans morphology in vaginal smears.

The morphology index (Mi) of Candida albicans cells was determined by microscopic image analysis in vaginal smears from 26 patients. The morphology of the cells typically showed a broad distribution of forms, but the mean Mi was greater than 2.0 in 23/26 instances, indicating a preponderance of pseudohyphal and hyphal forms. No association could be found between Mi and the clinical assessment of signs or symptoms of Candida infection. Comparison of these 26 patients with 43 others who had Candida-positive vaginal smears but with fewer than 15 fungal cells in the smear revealed significantly lower scores for vulvovaginal symptoms among the latter.

Candida albicans↗

Fungal morphology after treatment with itraconazole as a single oral dose in experimental vaginal candidosis in rats.

The therapeutic effect of a single, oral dose of itraconazole was studied in rats inoculated intravaginally with Candida albicans and in which an established vaginal infection was present. We used light microscopy, transmission and scanning electron microscopy to document the structural alterations in the 3 days after treatment. The most important observations include the speed (within 24 hours) with which itraconazole inhibits the further penetration of the fungus into the vaginal squamous epithelium, the ability of the drug to reach and structurally alter intracellularly located fungal elements, and the prolonged drug effect of a single dose leading to complete eradication of the fungus from the vagina within 3 days.

Administration, Oral↗

Non-identity and authentication of two major reference strains of Candida albicans.

It has been suggested recently that the two most widely used reference strains of Candida albicans (NCPF 3153 and B311) were derived from the same parental strain. However, records maintained at the PHLS Mycological Reference Laboratory suggest otherwise. In an attempt to resolve this contradiction, assessments were made of biotypes, resistogram patterns, morphotypes and restriction fragment length polymorphisms (RFLP) for nine isolates of NCPF 3153 and six of B311, obtained from 11 different centres. Biotyping results showed that with one exception (isolate No. 3, putatively derived from NCPF 3153), only strains derived from B311 were resistant to flucytosine at 12.5 micrograms ml-1 in agar. Moreover, strain No. 3 differed from other NCPF 3153 derivatives in its resistogram and RFLP patterns, which were indistinguishable from B311 isolates. It was concluded that the two reference strains were not derived from the same parental strain, and that they could be distinguished from each other by biotype, resistogram and RFLP patterns. Strains designated as B311 resembled each other closely, in contrast to NCPF 3153 isolates, which had variable resistogram and RFLP patterns. The simplest screening procedure for distinguishing B311 isolates was their resistance to flucytosine. Since test isolate No. 3 differed consistently from other putative NCPF 3153 isolates, it was concluded that its status was uncertain and that its designation as = NCPF 3153 should be discontinued.

Candida albicans↗

Sabouraud('s) agar.

'Sabouraud glucose agar' is the name recommended for present-day versions of the medium originally designed by Raymond Sabouraud. The title 'Sabouraud glucose agar' implies a medium comprising 1% (w:v) peptone, 4% (w:v) glucose and 1.5-2.0% (w:v) agar with a final pH of 5.6 and should not be applied to any other formulation, in the interests of inter-laboratory reproducibility. Use of the word 'dextrose' as a synonym for 'glucose' is not recommended. The colony forms, microscopic characteristics and other physiological properties of fungi cultivated on Sabouraud glucose agar may vary considerably according to the type of peptone used in the medium. The type of agar chosen and the conditions of autoclave sterilization are further obstacles to true standardization of this widely used mycological culture medium.

Agar↗

Long-term laboratory preservation of pathogenic yeasts in water.

A total of 1583 yeast isolates, mostly Candida albicans, has been maintained under sterile distilled water for periods ranging from 1 to 18 years. Overall, 71 (4.5%) of the isolates were not recoverable at 37 degrees C. Survival of the yeasts was 97% in the first 5 years and 96% after 10 years. Isolates of Candida krusei and Saccharomyces cerevisiae were particularly unlikely to survive storage in water and these species should be preserved by other means if they are to be kept for more than a few years. All of the Candida guilliermondii (n = 19) and Candida parapsilosis isolates (n = 51) survived water storage. The water preservation method is inexpensive and simple and is recommended for maintenance of most yeasts isolated from clinical material.

Candida↗

Reaction of Candida albicans cells of different morphology index with monoclonal antibodies specific for the hyphal form.

Two monoclonal antibodies (MAbs), 3D9 with reported specificity for Candida albicans hyphae, and 3B7 with reported specificity for morphological forms of C. albicans found in vivo, were tested by indirect immunofluorescence with C. albicans cells that were grown in 12 different environments (four different culture media incubated at various temperatures) and whose cellular morphology was estimated in terms of morphology index (Mi). Both MAbs reacted strongly with cells with Mi greater than 3.0, i.e., with pseudohyphal and hyphal forms, but in Eagle's medium at 26 degrees C and in a modified Sabouraud's broth medium at 30 degrees C, some reactivity was also found with cells of lower Mi (i.e., yeast forms). Therefore, it was concluded that the hyphal phenotype and the epitopes reactive with the MAbs were co-expressed but that the epitopes could also be expressed independently of the hyphal phenotype. The results confirm the propensity of C. albicans for variation of its surface antigenic composition.

Antibodies, Fungal↗

Quantitative microculture system with standardized inocula for strain typing, susceptibility testing, and other physiologic measurements with Candida albicans and other yeasts.

A method for physiologic testing of Candida albicans and other yeasts is described in which inocula with reproducible cell concentrations are prepared from cultures in a glucose-limited medium and growth turbidities of test cultures in microplates are expressed quantitatively as a percentage of control growth. The method gave good within-plate and run-to-run reproducibilities and was applicable both to strain phenotype discrimination in C. albicans and to susceptibility tests of yeasts with azole antifungal agents.

Agar↗