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A Fothergill

Publications and source records attributed to A Fothergill.

30 records · Page 2Linked to original sources
PubMed2000

A head-on comparison of the in vitro antifungal activity of conventional and lipid-based amphotericin B: a multicenter study.

A comparative study of conventional amphotericin B, Abelcet and AmBisome was performed using a microdilution format of the NCCLS M27-A methodology for susceptibility testing against 300 fungal isolates (152 yeasts, 148 filamentous fungi) in both RPMI-1640 and antibiotic medium #3 (AB3). The clinical isolates included Candida albicans (n=54), Candida glabrata (n=25), Candida parapsilosis (n=23), Candida krusei (n=19), Candida lusitaniae (n=14), Cryptococcus neoformans (n=5), Candida tropicalis (n=12), Aspergillus flavus (n=34), Aspergillus fumigatus (n=46) and 68 other filamentous fungi encompassing 22 different genera. The minimal inhibitory concentrations (MIC) for all drugs were defined as the lowest concentrations in which there was no visible growth. MICs were determined after 48 h for yeasts and 72 h for filamentous fungi. The mean MICs +/- standard error (microg/ml) for yeasts and filamentous fungi, respectively, were: Abelcet, 0.51+/-0.21, 4.34+/-0.61; AmBisome, 1.28+/-0.24, 5.68+/-0.57; amphotericin B, 0.29+/-0.11, 1.12+/-0.19, respectively. Overall, against both yeasts and filamentous fungi Abelcet proved to have more potent antifungal activity than AmBisome. Using AB3 as opposed to RPMI-1640 generally produced lower MIC values but did not have any effect on the order of relative activity with all of the antifungal agents tested. In conclusion, our data shows that Abelcet is more active than AmBisome against pathogenic yeast and filamentous fungi when assayed in AB3 in vitro. Comparison of the activities of these antifungals in experimental animal models is necessary to determine whether these in vitro findings are correlated with in vivo efficacy.

Amphotericin B↗
PubMed1999

Race, ethnicity and disasters in the United States: a review of the literature.

In this paper we synthesise past disaster research that addresses issues of race and ethnicity in the United States. Using an eight-stage typology to organise the findings, this literature review presents the results from a wide range of studies. The synthesis shows how various racial and ethnic groups perceive natural hazard risks and respond to warnings, how groups may be differentially affected, both physically and psychologically, and how disaster effects vary by race and ethnicity during the periods of emergency response, recovery and reconstruction. We show that studies have important findings, many illustrating that racial and ethnic communities in the US are more vulnerable to natural disasters, due to factors such as language, housing patterns, building construction, community isolation and cultural insensitivities. By presenting these studies together, we are able to witness patterns of racial and ethnic inequalities that may be more difficult to see or interpret in individual studies that take place in one specific time and place. We conclude the review with policy and research recommendations.

Disaster Planning↗
PubMed1999

Activities of sordarins in murine histoplasmosis.

Sordarins are new antifungals which inhibit fungal protein synthesis by blocking elongation factor 2. Three compounds were evaluated in a murine model of histoplasmosis. Immune-competent mice were infected intravenously with 10(6) to 10(8) CFU of Histoplasma capsulatum yeast cells. Mice were treated either orally with sordarins or fluconazole from day 2 through 8 after infection or intraperitoneally with amphotericin B during the same period. Protection was measured by increased rates of survival for 30 days after infection or reduction of lung or kidney tissue counts 9 days after infection. All three of the antifungal drugs tested were protective compared with controls. Sordarins were effective at doses as low as 2 mg/kg of body weight/day. This novel class of drugs compared favorably with amphotericin B and fluconazole for the treatment of histoplasmosis.

Amphotericin B↗
PubMed1998

KY-62, a polyene analog of amphotericin B, for treatment of murine candidiasis.

KY-62 is a water-soluble analog of amphotericin B. In vitro testing of five clinical isolates of Candida albicans showed KY-62 to have potency similar to that of amphotericin B. KY-62 was administered to mice infected intravenously with C. albicans. In vivo, KY-62 was effective in immunocompetent mice, with potency similar to that of amphotericin B. KY-62 was well tolerated up to 30 mg/kg of body weight per dose, an amount that would be lethal with amphotericin B. KY-62 was less effective in mice rendered neutropenic with 5-fluorouracil. The addition of flucytosine had little effect. KY-62 may have potential for clinical development.

Amphotericin B↗
PubMed1997

Treatment of murine Candida krusei or Candida glabrata infection with L-743,872.

L-743,872 is a broad-spectrum pneumocandin antifungal drug developed by Merck Research Co., and in the present work it was evaluated in vivo in murine models of Candida krusei and Candida glabrata infection. Mice were infected intravenously with two isolates of C. krusei and treated with fluconazole or L-743,872. Fluconazole was beneficial only in immune-competent mice infected with isolate 94-2696. At > 0.5 mg/kg of body weight/day, L-743,872 was effective against both infecting isolates in immune-competent and immune-suppressed mice. Against C. glabrata, L-743,872 was effective, at doses > or = 0.5 mg/kg, in reducing fungal cell counts in the kidneys but not in the spleen. L-743,872 has significant potential for clinical development.

Animals↗
PubMed1997

Multicenter evaluation of proposed standardized procedure for antifungal susceptibility testing of filamentous fungi.

A multicenter study was conducted to expand the generation and analysis of data that supports the proposal of a reference method for the antifungal susceptibility testing of filamentous fungi. Broth microdilution MICs of amphotericin B and itraconazole were determined in 11 centers against 30 coded duplicate pairs of Aspergillus spp., Fusarium spp., Pseudallescheria boydii, and Rhizopus arrhizus. The effect of inoculum density (approximately 10(3) and 10(4) CFU/ml), incubation time (24, 48, and 72 h), and procedure of MIC determination (conventional and colorimetric [Alamar Blue] evaluation of growth inhibition) on intra- and interlaboratory agreement was analyzed. Based on intra- (97 to 100%) and interlaboratory (94 to 95%) agreement for both drugs, the overall optimal testing conditions identified were determination of colorimetric MICs after 48 to 72 h of incubation with an inoculum density of approximately 10(4) CFU/ml. These testing conditions are proposed as guidelines for a reference broth microdilution method.

Antifungal Agents↗
PubMed1997

Candida and Torulopsis: a blinded evaluation of use of pseudohypha formation as basis for identification of medically important yeasts.

Seventy yeast isolates representing species in the genera Candida and Torulopsis but excluding Candida albicans were examined in three laboratories for production of pseudohyphae in Dalmau cultures. The microscopic morphology of the isolates was scrutinized by four individuals experienced in yeast identification and three inexperienced persons, all of whom were blinded as to the putative identification of the yeasts. For 49 (70%) of the 70 isolates, the seven observers recorded comparable scores for morphology, but 5 (7%) of the isolates showed extreme variation in recorded morphologies, from true hyphae formed to no pseudohyphae formed. Isolates of Candida parapsilosis and Torulopsis glabrata consistently did and did not form pseudohyphae, respectively: however, other Candida and Torulopsis spp. did not always express their expected morphologies. In 48 (19%) of 252 readings (seven observers), 36 isolates of Candida spp. were scored as forming no pseudohyphae, and in 22 (9.2%) of 238 readings, 34 isolates of Torulopsis spp. were recorded as forming true hyphae or pseudohyphae. These results show that pseudohypha formation is not a reliable characteristic for identification of yeasts at the genus level; we suggest that the merger of Torulopsis spp. into the genus Candida should be finally accepted.

Candida↗
PubMed1996

Bleomycin therapy of experimental disseminated candidiasis in mice.

Bleomycin, an antineoplastic agent, was found to be very effective in vitro against a variety of fungi, including Candida albicans. Mice were infected with C. albicans intravenously and then treated with various doses of bleomycin. No efficacy was shown by either prolongation of survival or reduction of tissue counts.

Animals↗
PubMed1995

Comparative and collaborative evaluation of standardization of antifungal susceptibility testing for filamentous fungi.

The purpose of the study was to evaluate the interlaboratory agreement of broth dilution susceptibility methods for five species of conidium-forming (size range, 2 to 7 microns) filamentous fungi. The methods used included both macro- and microdilution methods that were adaptations of the proposed reference method of the National Committee for Clinical Laboratory Standards for yeasts (m27-P). The MICs of amphotericin B, fluconazole, itraconazole, miconazole, and ketoconazole were determined in six centers by both macro- and microdilution tests for 25 isolates of Aspergillus flavus, Aspergillus fumigatus, Pseudallescheria boydii, Rhizopus arrhizus, and Sporothrix schenckii. All isolates produced clearly detectable growth within 1 to 4 days at 35 degrees C in the RPMI 1640 medium. Colony counts of 0.4 x 10(6) to 3.3 x 10(6) CFU/ml (mean, 1.4 x 10(6) CFU/ml) were demonstrated in 90% of the 148 inoculum preparations. Overall, good intralaboratory agreement was demonstrated with amphotericin B, fluconazole, and ketoconazole MICs (90 to 97%). The agreement was lower with itraconazole MICs (59 to 79% median). Interlaboratory reproducibility demonstrated similar results: 90 to 100% agreement with amphotericin B, fluconazole, miconazole, and ketoconazole MICs and 59 to 91% with itraconazole MICs. Among the species tested, the MICs for S. schenckii showed the highest variability. The results of the study imply that it may be possible to develop a reference method for antifungal susceptibility testing of filamentous fungi.

Aspergillus↗
PubMed1994

Resistance of Candida albicans to fluconazole during treatment of oropharyngeal candidiasis in a patient with AIDS: documentation by in vitro susceptibility testing and DNA subtype analysis.

We describe a patient with recurrent episodes of oropharyngeal candidiasis who required progressively higher doses of fluconazole to control and infection. The patient was treated for 14 infections over a 2-year period with doses of fluconazole that ranged from 100 to 800 mg per day. Clinical response, two methods of in vitro susceptibility testing, and molecular epidemiologic techniques were evaluated for 12 of the 14 episodes. Ultimately, the patient became unresponsive clinically to a dose of 800 mg of fluconazole per day. In vitro susceptibility testing of isolates obtained during these successive episodes of infection revealed the development of resistance to fluconazole, and molecular epidemiologic techniques confirmed the persistence of the same Candida albicans strain throughout all 12 episodes.

AIDS-Related Opportunistic Infections↗
PubMed1994

Multisite reproducibility of colorimetric broth microdilution method for antifungal susceptibility testing of yeast isolates.

MICs of fluconazole and amphotericin B were determined independently for 100 coded yeast isolates by each of six laboratories to determine reproducibility of results by using a colorimetric oxidation-reduction-based broth microdilution test. In addition, each site tested five quality control isolates on at least four different occasions during the study. Results agreed within a three-dilution range (mode +/- 1 log2 dilution) for 96.2% of fluconazole tests and 92.7% of amphotericin B tests. Agreement among tests with the quality control isolates was 99.4% with fluconazole and 98.6% with amphotericin B. These results indicate that the colorimetric microdilution method is reproducible among laboratories.

Amphotericin B↗