PubMed Health⌕ Search

Biomedical subjects

Elizabeth Dodds Ashley

Publications and source records attributed to Elizabeth Dodds Ashley.

5 recordsLinked to original sources

Cost savings with implementation of PNA FISH testing for identification of Candida albicans in blood cultures.

Antifungal expenditures are substantial for many hospitals. Using caspofungin for the treatment of candidemia accounts for a sizable proportion of the costs. A cost minimization study that used a decision analytic model was done to compare in-hospital diagnosis and treatment costs using the Candida albicans peptide nucleic acid fluorescence in situ hybridization (PNA FISH) test versus the C. albicans screen test for differentiating C. albicans from non-albicans Candida species bloodstream infections. Assuming physician notification of yeast identity concurrent with blood culture positivity, potential savings resulting from use of the C. albicans PNA FISH test compared with the C. albicans screen test averaged $1837 per patient treated, although laboratory costs for doing the C. albicans PNA FISH test ($82.72) exceeded those for the C. albicans screen test ($2.83). Savings were realized through a decrease in antifungal drug costs, particularly caspofungin. Incorporating the C. albicans PNA FISH test as part of the initial identification algorithm for yeasts recovered from blood can result in substantial savings for hospitals.

Antifungal Agents↗

Inhaled azithromycin therapy.

The treatment of pulmonary infectious diseases with pharmaceutical aerosols is an attractive option considering the accessibility of the lungs for topical drug delivery. Aerosols have been targeted to the lungs for the treatment of asthma with great success. Current therapies for other diseases, including Pseudomonas aeruginosa, Pneumocystis jirovecii (formerly Pneumocystis carinii), and mycobacterial infections, remain suboptimal due to the efficacy/safety profile. This may be improved by aerosol targeted pulmonary drug delivery. Azithromycin is a broad spectrum antibiotic that acts by inhibiting protein synthesis. It is associated with side effects that might be avoided by aerosol delivery to the lungs. In the present study three concentrations of azithromycin (10, 50, and 100 mg/mL) were delivered from three nebulizers (Acorn II, Updraft, and LC Plus) operated at 8 L/min. Particles size analyses were conducted by inertial impaction and laser diffraction. In addition, emitted doses were determined. A linear proportionality existed across the concentration range between nominal dose and both fine particle dose/fraction and emitted dose, with R2 > 0.999 in all cases. The mass median aerodynamic diameter increased from 1.4 to 1.9 microm between 10 and 100 mg/mL of azithromycin solution concentration for the Acorn II. The particle size distributions were not all log-normally distributed. The median particle size delivered from the devices was largest for the Updraft (2.8 microm) and smallest for the Acorn II (1.9 microm) for 100 mg/mL azithromycin solution concentrations. The efficiencies of small particle delivery (%<4.7 microm) were as follows, LC Plus = Acorn II (85%) > UpDraft (75%). However, the emitted dose from the LC Plus (55 mg/min) was higher than the Acorn II (31 mg/min) to maximize lung exposure to the aerosol, small median diameters and broad particle size distributions would be most effective. This study demonstrates that the dose delivered to the lungs will be maximized, under the current operating conditions by adopting the LC Plus, and high (100 mg/mL) azithromycin concentrations.

Administration, Inhalation↗

Design of aerosolized amphotericin b formulations for prophylaxis trials among lung transplant recipients.

BACKGROUND: Emphasis has been placed on the need for antifungal prophylaxis when transplanted organs are directly exposed to the environment. In lung transplantation, one strategy for prevention has been aerosolization of polyenes into the lung. Despite widespread use of amphotericin B aerosols, there are still few studies on how to validate their effectiveness or optimize pharmacokinetics. METHODS: We compared results of several of our own studies of lung transplant recipients receiving formulations of amphotericin B with results of other studies. RESULTS: Recent aerosol studies suggest that aerosols of a lipid formulation of amphotericin B are safe and better tolerated than is amphotericin B deoxycholate. Their use in prophylaxis is associated with very few pulmonary fungal infections. CONCLUSION: This safe drug delivery at a local body site to directly protect the transplanted organ without systemic antifungal drug exposure is attractive from a cost and toxicity standpoint. However, careful multicenter, comparative studies are still needed to ensure that this strategy is consistently successful.

Aerosols↗

Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients.

BACKGROUND: Aerosolized administrations of amphotericin B deoxycholate (AmBd) and amphotericin B lipid complex (ABLC) in lung transplant recipients were compared for safety and tolerability. The incidence of invasive fungal infections in patients receiving aerosolized amphotericin B formulations as sole prophylaxis was determined. METHODS: A prospective, randomized (1:1), double-blinded trial was conducted with 100 subjects. AmBd and ABLC were administered postoperatively by nebulizer at doses of 25 mg and 50 mg, respectively, which were doubled in mechanically ventilated patients. The planned treatment was once every day for 4 days, then once per week for 7 weeks. Treatment-related adverse events and invasive fungal infections were quantitated for 2 months after study drug initiation. RESULTS: Intent-to-treat analysis revealed study drug was discontinued for intolerance in 6 of 49 (12.2%) and 3 of 51 (5.9%) patients in the AmBd- and ABLC-treated groups, respectively (p=0.313). Subjects receiving AmBd were more likely to have experienced an adverse event (odds ratio 2.16, 95% confidence interval 1.10, 4.24, p=0.02). Primary prophylaxis failure within 2 months of study drug initiation was observed in 7 of 49 (14.3%) AmBd-treated patients and 6 of 51 (11.8%) ABLC-treated patients. No fungal pneumonias were observed. Only two (2%) patients experienced documented primary prophylaxis failure with Aspergillus infections within the follow-up period. CONCLUSIONS: Both aerosol AmBd and ABLC appear to be associated with a low rate of invasive pulmonary fungal infection in the early posttransplant period. Patients receiving ABLC were less likely to experience a treatment-related adverse event.

Adolescent↗

Aspergillus fumigatus empyema, arthritis, and calcaneal osteomyelitis in a lung transplant patient successfully treated with posaconazole.

A 64-year-old male with Aspergillus fumigatus infection that had disseminated from the lung to the ankle and adjacent bone was treated successfully with posaconazole after therapy with itraconazole and amphotericin B lipid complex failed. Marked clinical improvement occurred within 6 weeks of initiation of posaconazole therapy; after 6 months, infection had resolved at all sites. The patient has had no recurrence of infection.

Antifungal Agents↗