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Annette W Fothergill

Publications and source records attributed to Annette W Fothergill.

17 recordsLinked to original sources
PubMed2006

Posaconazole prophylaxis in experimental systemic zygomycosis.

Three isolates of zygomycetes belonging to two different genera (Rhizopus oryzae and Absidia corymbifera) were used to produce a systemic infection in neutropenic mice. On days -2 and -1 and at 2 h prior to infection, the mice received either posaconazole (POS) at doses ranging from 20 to 80 mg/kg of body weight/day or amphotericin B (AMB) at 1 mg/kg/day. Antifungal drug efficacy was assessed by determination of the prolongation of survival, determination of the percentage of infected organs (brain, lung, spleen, and kidney), and histological examination for the number of infection foci and their sizes in brain and kidney tissues. AMB significantly prolonged the survival of mice infected with all isolates. POS significantly prolonged the survival of mice infected with zygomycetes. Cultured organs from mice infected with R. oryzae were all positive, while treated mice challenged with A. corymbifera generally showed lower percentages of infected organs compared with the percentages for the controls. Zygomycete isolates established an active infection (the presence of hyphae) in the brains and the kidneys of all controls. In mice challenged with R. oryzae, both antifungal drugs were effective at reducing the number and the size of infection foci in the kidneys. Only AMB reduced the numbers, but not the sizes, of infection foci in the brain. Finally, both drugs significantly reduced the numbers and the sizes of infection foci in both tissues of mice infected with A. corymbifera. Our data suggest that prophylaxis with POS has some potential to prevent zygomycosis.

Absidia↗
PubMed2006

Antifungal susceptibility testing.

Antifungal susceptibility testing has been in routine use now for more than 15 years and has become a useful tool for clinicians who are faced with difficult treatment decision. Although most clinicians order susceptibility testing, much confusion still exists regarding the use of the results. Sufficient data have been generated to determine susceptibility trends for specific fungi against specific agents, but correlation data are minimal. Despite the lack of correlation data, antifungal susceptibility testing continues to provide useful information to assist with patient care.

Antifungal Agents↗
PubMed2006

Miconazole: a historical perspective.

Miconazole is an imidazole that has been successfully used for over 30 years for the treatment of superficial and cutaneous disease. This agent is distinguished from other azoles by possessing two mechanisms of action. The first mechanism is shared with other azoles and involves the inhibition of ergosterol synthesis. Another mechanism involves inhibition of peroxidases, which results in the accumulation of peroxide within the cell resulting in cell death. Susceptibility patterns for miconazole demonstrate that yeast fungi remain largely susceptible even in light of repeated exposures. Despite the release of newer azoles and other classes of antifungals, miconazole remains a highly prescribed treatment for vaginal candidiasis.

Animals↗
PubMed2005

In vitro activities of new and established triazoles against opportunistic filamentous and dimorphic fungi.

The in vitro activities of three new triazoles were determined and compared to those of itraconazole and fluconazole against 306 clinical isolates of Blastomyces dermatitidis, Cladophialophora carrionii, Coccidioides immitis, Fonsecaea pedrosoi, Fusarium spp., Histoplasma capsulatum, Paecilomyces lilacinus, Pseudallescheria boydii and Sporothrix schenckii. Minimum inhibitory concentrations (MIC) were determined by a broth macrodilution method of the National Committee for Clinical Laboratory Standards M38-A procedure. Itraconazole (geometric mean MIC, 0.16-0.65 microg/ml), voriconazole (geometric mean MIC, 0.18-1.44 microg/ml), ravuconazole (geometric mean MIC, 0.18-1.09 microg/ml), and posaconazole (geometric mean MIC, 0.18-1.38 microg/ml), had relatively uniform values showing potent in vitro inhibitory activity against B. dermatitidis, C. carrionii, C. immitis, F. pedrosoi, H. capsulatum, and S. schenckii. The in vitro activity was variable with strains of P. boydii, P. lilacinus and Fusarium spp.

Antifungal Agents↗
PubMed2005

Efficacy of caspofungin against Aspergillus terreus.

We investigated the in vitro and in vivo activities of caspofungin against Aspergillus terreus. The drug increased survival and reduced tissue fungal burden in neutropenic mice. Therefore, our data support the role of caspofungin in treating systemic infections due to this emerging pathogen.

Animals↗
PubMed2005

Caspofungin in combination with amphotericin B against Candida glabrata.

The effects of caspofungin combined with amphotericin B were investigated with Candida glabrata. Although in vitro experiments showed an indifferent interaction, the combination regimen was the only therapeutic approach yielding organ sterilization in a murine candidemia model.

Amphotericin B↗
PubMed2005

Scedosporium apiospermum soft tissue infection successfully treated with voriconazole: potential pitfalls in the transition from intravenous to oral therapy.

An immunocompromised patient with an invasive soft tissue infection due to Scedosporium apiospermum was successfully treated with voriconazole and surgical debridement. After transition from intravenous to oral therapy, successive adjustments of the oral dose were required to achieve complete resolution. For soft tissue infections due to molds characterized by thin, septate hyphae branching at acute angles, voriconazole should be considered a first-line antifungal agent. The potential usefulness of plasma voriconazole levels for guiding optimal therapy should be investigated.

Administration, Oral↗
PubMed2004

Candida glabrata is an emerging cause of oropharyngeal candidiasis in patients receiving radiation for head and neck cancer.

Oropharyngeal candidiasis (OPC) is relatively common in patients receiving radiation for head and neck cancer occurring in approximately 25% of patients. Candida albicans has been described as the primary infecting organism. Recently, other organisms, particularly Candida glabrata, have emerged as causative agents of OPC among immunocompromised patients. This study describes the characteristics of 6 patients with head and neck cancer treated with radiotherapy at our institution, who were found to have Candida glabrata-associated OPC and their responses to oral fluconazole. All 6 patients were successfully treated with oral fluconazole. However, most did not respond to the usual dose of 100 mg/day necessitating doses ranging from 200 to 800 mg/day to achieve clinical cure. All 3 patients receiving radiation only were successfully treated with up to 200 mg/day; 2 of 3 patients receiving concomitant chemoradiation required doses ranging from 400 to 800 mg/day. As with systemic infection, previous fluconazole use appears to be a risk factor for this infection, but not with all patients.

Adult↗
PubMed2004

In vitro activities of voriconazole in combination with three other antifungal agents against Candida glabrata.

Candida glabrata has recently emerged as a significant pathogen involved in both superficial and deep-seated infections. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of voriconazole (VOR) in combination with terbinafine (TRB), amphotericin B (AMB), and flucytosine (5FC) against 20 clinical isolates of C. glabrata. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or = 0.50, was observed in 75% of VOR-TRB, 10% of VOR-AMB, and 5% of VOR-5FC interactions. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. In particular, the MICs were reduced to < or = 1.0 microg/ml as a result of the combination for all isolates for which the AMB MIC at the baseline was > or = 2.0 microg/ml. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were greater that those produced by each drug alone. Finally, killing curves showed that VOR-AMB exhibited synergistic interactions, while VOR-5FC sustained fungicidal activities against C. glabrata. These studies demonstrate that the in vitro activity of VOR against this important yeast pathogen can be enhanced upon combination with other drugs that have different modes of action or that target a different step in the ergosterol pathway. Further studies are warranted to elucidate the potential beneficial effects of such combination regimens in vivo.

Amphotericin B↗
PubMed2004

Interlaboratory comparison of results of susceptibility testing with caspofungin against Candida and Aspergillus species.

Seventeen laboratories participated in a study of interlaboratory reproducibility with caspofungin microdilution susceptibility testing against panels comprising 30 isolates of Candida spp. and 20 isolates of Aspergillus spp. The laboratories used materials supplied from a single source to determine the influence of growth medium (RPMI 1640 with or without glucose additions and antibiotic medium 3 [AM3]), the same incubation times (24 h and 48 h), and the same end point definition (partial or complete inhibition of growth) for the MIC of caspofungin. All tests were run in duplicate, and end points were determined both spectrophotometrically and visually. The results from almost all of the laboratories for quality control and reference Candida and Aspergillus isolates tested with fluconazole and itraconazole matched the NCCLS published values. However, considerable interlaboratory variability was seen in the results of the caspofungin tests. For Candida spp. the most consistent MIC data were generated with visual "prominent growth reduction" (MIC(2)) end points measured at 24 h in RPMI 1640, where 73.3% of results for the 30 isolates tested fell within a mode +/- one dilution range across all 17 laboratories. MIC(2) at 24 h in RPMI 1640 or AM3 also gave the best interlaboratory separation of Candida isolates of known high and low susceptibility to caspofungin. Reproducibility of MIC data was problematic for caspofungin tests with Aspergillus spp. under all conditions, but the minimal effective concentration end point, defined as the lowest caspofungin concentration yielding conspicuously aberrant hyphal growth, gave excellent reproducibility for data from 14 of the 17 participating laboratories.

Antifungal Agents↗
PubMed2002

In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes.

In vitro antifungal susceptibility testing results of a new antifungal triazole, posaconazole (POS), were compared to results with amphotericin B (AMB), itraconazole (ITC), voriconazole (VRC), and fluconazole (FLC) against clinical agents of zygomycosis. The MICs of POS at which 50% and 90% of the isolates were inhibited were 0.25 and 4 microg/ml, respectively. POS was significantly more active than VRC and FLC and slightly more active than ITC. The results suggest that POS has significant potential for clinical development against the zygomycetes.

Amphotericin B↗
PubMed2002

In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp.

The interaction between caspofungin acetate and voriconazole was studied in vitro by using 48 clinical Aspergillus spp. isolates obtained from patients with invasive aspergillosis. MICs were determined by the NCCLS broth microdilution method. Synergy, defined as a fractional inhibitory concentration (FIC) index of <1, was detected in 87.5% of the interactions; an additive effect, defined as an FIC index of 1.0, was observed in 4.2% of the interactions; and a subadditive effect, defined as an FIC index of 1.0 to 2.0, was found in 8.3% of the interactions. No antagonism was observed. Animal models are required to validate the in vivo significance of these in vitro data presented for the combination of caspofungin and voriconazole.

Anti-Bacterial Agents↗
PubMed2002

In vitro activities of terbinafine in combination with fluconazole, itraconazole, voriconazole, and posaconazole against clinical isolates of Candida glabrata with decreased susceptibility to azoles.

A checkerboard microdilution method, performed according to the recommendations of the National Committee for Clinical Laboratory Standards, was used to study the in vitro interaction of terbinafine (TRB) with fluconazole (FLU), itraconazole (ITRA), voriconazole (VRC), and posaconazole (PSZ) in 24 isolates of Candida glabrata with decreased susceptibility to azoles isolated from the oral cavities of human immunodeficiency virus patients. Synergy, defined as a fractional inhibitory concentration index of < or =0.5, was observed in 17% of TRB-FLU interactions, 21% of TRB-ITRA interactions, 33% of TRB-VRC interactions, and 12% of TRB-PSZ interactions. Where synergy was not achieved, there was still a decrease in the MIC of one or both drugs when used in combination. Antagonism was not observed in any drug combination. Clinical studies are warranted to elucidate the potential utility of these combination therapies.

Antifungal Agents↗
PubMed2002

Candida glabrata oropharyngeal candidiasis in patients receiving radiation treatment for head and neck cancer.

Candida glabrata colonization is common in patients receiving radiation treatment for head and neck cancer, but to our knowledge has never been described as the infecting organism with oropharyngeal candidiasis (OPC). This study presents the first three patients described with C. glabrata OPC in this patient population. Patient 1 developed C. glabrata OPC and required fluconazole, 800 mg/day, for clinical resolution. Antifungal susceptibility testing revealed a MIC of fluconazole of >64 microg/ml. Elapsed time from initial culturing to treatment decision was 7 days. Patients 2 and 3 developed C. glabrata OPC. They were patients in a study evaluating OPC infections, and cultures were taken immediately. CHROMagar Candida plates with 0, 8, and 16 microg of fluconazole/ml were employed for these cultures. Lavender colonies, consistent with C. glabrata, grew on the 0- and 8-microg plates but not on the 16-microg plate from patient 2 and grew on all three plates from patient 3. Based on these data, a fluconazole dose of 200 mg/day was chosen for patient 2 and a dose of 400 mg/day was chosen for patient 3, with clinical resolution in both. Elapsed time from initial culturing to treatment decision was 2 days. C. glabrata does cause OPC in head and neck radiation treatment patients, and the use of fluconazole-impregnated chromogenic agar may significantly reduce treatment decision time compared to that with conventional culturing and antifungal susceptibility testing.

Adult↗
PubMedDate not supplied

In vitro efficacy of lufenuron against filamentous fungi and blood concentrations after PO administration in horses.

Lufenuron is a benzoylphenyl urea-derived insecticide that has been recently introduced as a novel treatment for fungal infections in horses. The purposes of this study were to determine (1) the in vitro efficacy of lufenuron against Aspergillus and Fusarium spp. and (2) the ability of lufenuron to reach efficacious blood concentrations after PO administration in horses. Fungal colonies isolated from diseased equine corneas were tested against lufenuron solutions up to 700 microg/mL. Twenty-one adult horses received 1 of 3 PO lufenuron treatment regimens: 5 mg/kg body weight (BW) q24h for 3 days, 20 mg/kg BW q24h for 3 days, or 60 mg/ kg BW q24h for 1 day. Blood samples were collected up to 96 hours after drug administration and analyzed by high-performance liquid chromatography. Statistical analyses of lufenuron blood concentrations were performed by analysis of variance and Fischer's Least Significant Difference test, with statistical significance set at P < .05. Lufenuron showed no effect on the in vitro growth of Aspergillus or Fusarium spp. Lufenuron was detected in the blood of all but 1 horse and showed no adverse effects. The maximum blood lufenuron concentration (83.5 +/- 58.7 microg/L) was lower than the concentrations proven to be ineffective in vitro in this study. Further therapeutic use of lufenuron as an antifungal agent in horses should be based on proven efficacy against specific strains of clinically relevant fungi with pharmacokinetic data demonstrating sufficient lufenuron concentrations in target tissues.

Administration, Oral↗