Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new sporanox research articles will be listed here shortly after becoming available to us.
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Medical research on sporanox
Int J Pharm. 2008 May 14;
Yang W, Tam J, Miller DA, Zhou J, McConville JT, Johnston KP, Williams RO
A nebulized dispersion of amorphous, high surface area, nanostructured aggregates of itraconazole (ITZ):mannitol:lecithin (1:0.5:0.2, w/w) yielded improved bioavailability in mice. The ultra-rapid freezing (URF) technique used to produce the nanoparticles was found to molecularly disperse the ITZ with the excipients as a solid solution. Upon addition to water, ITZ formed a colloidal dispersion suitable for nebulization, which demonstrated optimal aerodynamic properties for deep lung delivery and high lung and systemic levels when dosed to mice. The ITZ nanoparticles produced supersaturation levels 27 times the crystalline solubility upon dissolution in simulated lung fluid. A dissolution/permeation model indicated that the absorption of 3mum ITZ particles is limited by the dissolution rate (BCS Class II behavior), while absorption is permeation-limited for more rapidly dissolving 230nm particles. The predicted absorption half-life for 230nm amorphous ITZ particles was only 15min, as a result of the small particle size and high supersaturation, in general agreement with the in vivo results. Thus, bioavailability may be enhanced, by decreasing the particle size to accelerate dissolution and increasing permeation with (1) an amorphous morphology to raise the drug solubility, and (2) permeability enhancers.
Spherules, Hyphae, and Air-Crescent Sign.
Am J Med Sci. 2008 Jun; 335(6): 504-506
Tonelli AR, Khalife WT, Cao M, Young VB
Coccidioidomycosis is endemic in the southwestern United States, resulting in 100,000 infections annually. The majority of these infections are asymptomatic or manifest as community-acquired pneumonia. In rare cases, patients can present with a mononuclear-cell predominant pyopneumothorax. The presence of spherules in tissue specimens is pathognomonic of this condition. A 72-year-old man born in Arizona with a heavy smoking history, presented with a 1-month history of weakness, night sweats, exertional dyspnea, and left pleuritic chest pain. The physical examination was remarkable for decreased breath sounds and dullness to percussion at the left lung base. His initial laboratory examination showed leukocytosis, eosinophilia, and elevated C-reactive protein. Computed tomography of the chest revealed a left lower lobe infiltrate, a cavity with air-crescent sign and hydropneumothorax. The pleural fluid was sampled and revealed an eosinophilic exudate with normal pH. Bacterial and fungal cultures of the pleural fluid were negative. Biopsy of the cavity wall showed chronic inflammation, fungal hyphae, and rare spherule-like structures. The surgical specimen culture grew Coccidioides immitis. Complement fixation for coccidioidomycosis performed on a serum sample was positive at a titer of 1:2 but a latex agglutinin test was negative. The patient was diagnosed with chronic fibrocavitary pneumonia with pyopneumothorax secondary to C. immitis infection and discharged on itraconazole for 1 year. Coccidioidomycosis can present in a variety of forms and should be part of the differential diagnosis in patients presenting with cavitation, air-crescent sign, eosinophilic pleural effusion, and hyphae and spherules on the tissue specimen. Chronic fibrocavitary pneumonia should be especially considered in patients who lived in endemic areas and have risk factors such as diabetes mellitus or pulmonary fibrosis related to smoking.
In vitro antifungal drug susceptibilities of dermatophytes microconidia and arthroconidia.
J Antimicrob Chemother. 2008 Jun 13;
Coelho LM, Aquino-Ferreira R, Maffei CM, Martinez-Rossi NM
Objectives Arthroconidia have been considered as the primary cause of infection by dermatophytes. However, the in vitro antifungal testing evaluates the responses mainly of microconidia or hyphae, and dermatophytes in vivo often produce arthroconidia, a cellular structure presumably more resistant to antifungals. The aim of this study was to compare the in vitro susceptibility of microconidia and arthroconidia of Trichophyton rubrum, Trichophyton tonsurans and Trichophyton equinum to griseofulvin, itraconazole, terbinafine, fluconazole, amphotericin B and hygromycin B. Methods Microconidia and arthroconidia were produced in vitro, and their susceptibility to each drug was evaluated by assessing the CLSI M38-A broth microdilution method. Results Arthroconidia of all strains analysed appeared to be more resistant to fluconazole, griseofulvin and itraconazole than microconidia. The MIC of terbinafine was the same for microconidia and arthroconidia for all strains, and the MIC of amphotericin B for microconidia and arthroconidia was the same for isolates of T. equinum and T. tonsurans, but differed for T. rubrum. Finally, the level of resistance of microconidia for all strains towards the antibiotic hygromycin B was from 25 to 400 mg/L. Conclusions The difference in the susceptibility between microconidia and arthroconidia depends on the drug and on the strain, and may be one of the causes of therapeutic failure. Also, the level of resistance to the antibiotic hygromycin B presented by microconidia of these isolates will allow the use of hygromycin resistance as a dominant marker in fungal transformation procedures in future studies of gene function.
Antifungal Susceptibility for Common Pathogens of Fungal Keratitis in Shandong Province, China.
Am J Ophthalmol. 2008 Jun 9;
Xie L, Zhai H, Zhao J, Sun S, Shi W, Dong X
PURPOSE: To analyze common pathogens of fungal keratitis and results of antifungal drug sensitivity test in Shandong Province, China and provide guidance for appropriate choice of antifungal drugs in clinic. DESIGN: Retrospective, noncomparative study. METHODS: The pathogens isolated from 674 fungal keratitis patients between January 1, 2001 and December 31, 2006 were cultured and identified in Shandong Eye Institute, of which some common strains were tested for sensitivity to antifungal drugs. RESULTS: Fungi were positively cultured in 549 (81.5%) patients, in which the dominating pathogen was genus Fusarium (77.6%), with F. solani (37.3%), F. moniliforme (30.0%), and F. oxysporum (27.9%) being common species; Fusarium was mostly sensitive to natamycin, next to amphotericin B, and then to terbinafin. The second common pathogen was genus Aspergillus (10.8%), in which the main species were A. flavus (49.2%) and A. fumigatus (35.6%); Aspergillus was mostly sensitive to natamycin, next to terbinafin, and then to amphotericin B. Relatively, both Fusarium and Aspergillus were insensitive to ketoconazole, miconazole, itraconazole, fluconazole, and fluorocytosine. CONCLUSIONS: Fusarium is the most common pathogen of fungal keratitis, followed by Aspergillus, in Shandong Province, China. Natamycin is still the first choice in the treatment of hyphomycetic keratitis. Fusarium and Aspergillus are also sensitive to amphotericin B and terbinafin. Early diagnosis and treatments are vital to good prognosis in the treatment of fungal keratitis.
Kansenshogaku Zasshi. 2008 May; 82(3): 220-3
Horikawa K, Kudo H, Ishihara S, Miyakawa T, Kawaguchi T, Mitsuya H
Aspergillosis of the bone is rare and resistant to treatment. We report a case of Aspergillus infection of the masticator space including mandibular bone in a diabetic adult. After extraction of a posterior tooth, the patient began to suffer from facial pain. The pain worsened in spite of antibiotic treatment. The results of serum tests and biopsy showed an invasive aspergillosis of the left masticator space including the mandibular bone six months after the onset. Although invasive aspergillosis can be fatal, the infection in our case responded to itraconazole treatment. Even in diabetes mellitus, invasive aspergillosis may occur after surgical interventions such as tooth extraction.
Rev Soc Bras Med Trop. 2008 Mar-Apr; 41(2): 158-62
Silva PR, Rabelo RA, Terra AP, Teixeira DN
This study identified Cryptococcus neoformans varieties isolated from 35 patients at teaching hospital of the Federal University of the Triângulo Mineiro and evaluated the susceptibility to antifungal agents among these samples using the protocol M27-A2 from the National Committee for Clinical Laboratory Standards. The gattii variety was identified in 11.4% of the cases (n = 4). The minimum inhibitory concentration (mg/ml) of Cryptococcus neoformans neoformans isolates ranged from 0.062 to 2.000 (amphotericin B), 0.250 to 8.000 (fluconazole), 0.062 to 1.000 (itraconazole) and 0.125 to 1.000 (ketoconazole). The gattii variety presented a minimum inhibitory concentration range of 0.125 to 2.000 (amphotericin B), 0.250 to 16.00 (fluconazole), 0.062 to 1.000 (itraconazole) and 0.125 to 4.000 (ketoconazole). Two isolates resistant to itraconazole and two resistant to amphotericin B (one isolate of each variety per antifungal agent) were found. These data show the importance of determining the variety and minimum inhibitory concentration of Cryptococcus neoformans isolates, in order to monitor resistance development and enable better treatment for cryptococcosis.
Aspergillosis of a dog genital tract-Case report.
Anim Reprod Sci. 2008 May 2;
Siemieniuch MJ, Skarzynski DJ, Kozdrowski R
The information about aspergillosis locations in the reproductive organ is scarce. This short paper deals with aspergillosis in the dog genital tract with hyphae present in semen. There are two therapy schemes used in visceral mycoses, non-invasive treatment and surgical intervention. Considering the future reproductive career of the dog, we decided on antifungal drugs administration. Based on the microbiological results, we administered amoxycillin with clavulonate (Synulox((R)) 500mg, twice daily) orally. Itraconazole was used as an antimycological agent (Orungal((R)), 100mg, twice daily) every other week. In 8th week of therapy no Aspergillus spp. growth was noted, yet slight Penicillium growth was observed. After 12 weeks of treatment, no fungus growth was present. Neither spores or hyphae were seen in the microscopic examination. Three months after the termination of the therapy, the dog mated with two females. In one case, unifetal pregnancy was diagnosed by ultrasound examination on day 42 after mating. Due to purulent discharge on day 45 after mating, the owner decided to terminate the pregnancy. In the other case, severe pyometra appeared 12 days after the second mating and the owner decided to put the female to sleep. The pathogen eradication from the ejaculates may be treated as a serious success, yet the lack of litters after mating calls for an explanation and consequences of Aspergillus spp. infection need to be considered.
Common tinea infections in children.
Am Fam Physician. 2008 May 15; 77(10): 1415-20
Andrews MD, Burns M
The common dermatophyte genera Trichophyton, Microsporum, and Epidermophyton are major causes of superficial fungal infections in children. These infections (e.g., tinea corporis, pedis, cruris, and unguium) are typically acquired directly from contact with infected humans or animals or indirectly from exposure to contaminated soil or fomites. A diagnosis usually can be made with a focused history, physical examination, and potassium hydroxide microscopy. Occasionally, Wood's lamp examination, fungal culture, or histologic tissue examination is required. Most tinea infections can be managed with topical therapies; oral treatment is reserved for tinea capitis, severe tinea pedis, and tinea unguium. Topical therapy with fungicidal allylamines may have slightly higher cure rates and shorter treatment courses than with fungistatic azoles. Although oral griseofulvin has been the standard treatment for tinea capitis, newer oral antifungal agents such as terbinafine, itraconazole, and fluconazole are effective, safe, and have shorter treatment courses.
Trans Am Clin Climatol Assoc. 2007; 118: 175-85
Gallin JI, Zarember K
Chronic Granulomatous Disease (CGD) is a rare disorder caused by mutations in the NADPH oxidase. The CGD phenotype includes granuloma formation and susceptibility to infection with microorganisms including Aspergillus. The immune adjuvant interferon-gamma and the antifungal agent itraconazole have reduced the incidence of infections in CGD. Studies using CGD phagocytes have shown that reactive oxygen species (ROS), products of the NAPDH oxidase, are critical for killing Aspergillus hyphae. But despite lack of ROS production, CGD patients generally only get infected with Aspergillus after heavy exposure. To study why CGD patients are not infected with Aspergillus more frequently we studied host defense against this ubiquitous mold further. We found that neutrophil lactoferrin is fungistatic for Aspergillus fumigatus spores by chelation of iron, an essential growth factor. Thus, the neutrophil employs both nonoxidative (lactoferrin) and oxidative (hydrogen peroxide) defense mechanisms against A. fumigatus spores and hyphae, respectively.
Fatal Hepatitis After Long-Term Pulse Itraconazole Treatment for Onychomycosis (July/August).
Ann Pharmacother. 2008 Jun 3;
Tuccori M, Bresci F, Guidi B, Blandizzi C, Del Tacca M, Di Paolo M
OBJECTIVE: To report the occurrence of acute cytolytic hepatitis in a patient exposed to pulse itraconazole therapy for 24 weeks and provide a concise review of the literature on cases of itraconazole-induced hepatitis. CASE SUMMARY: A 61-year-old woman with no apparent risk factors for liver injury developed acute hepatitis one week after the final dose of a long-term course of pulse itraconazole therapy (200 mg orally twice daily, 1 wk on, 3 wk off, for 24 wk) for onychomycosis. Monitoring of liver enzymes was not performed during the treatment period. Serologic evaluations on presentation ruled out infectious diseases or other etiological factors. Liver function tests showed alanine aminotransferase 3330 U/L, aspartate aminotransferase 3250 U/L, and bilirubin 21 mg/dL. Liver function continued to deteriorate, and the patient underwent liver transplantation 17 days after admission. Her liver displayed reduced volume and there was a mild accumulation of ascitic fluid in the retroperitoneal cavity. Histologic evaluation showed massive panlobular necrosis. Complications occurred after transplantation and a rejection crisis worsened the clinical picture until the patient died about 4 months later. Use of the Naranjo probability scale showed the relationship of itraconazole therapy and the occurrence of acute hepatitis as probable. DISCUSSION: Itraconazole pulse therapy for onychomycosis appears to be at least as effective as and safer than a continuous treatment regimen, particularly from the perspective of potential liver damage. Only one case of severe symptomatic hepatitis occurring after pulse therapy with itraconazole for onychomycosis and requiring transplantation has been reported previously. In that case, as well as the one reported here, hepatitis symptoms occurred after completion of long-term treatment in patients who were asymptomatic both before and during therapy. CONCLUSIONS: Prolonged exposure to itraconazole, administered either continuously or intermittently, may precipitate severe and irreversible hepatotoxic events. Accordingly, careful monitoring of liver function parameters should be performed both during and after treatment when onychomycosis requires prolonged itraconazole administration, even in asymptomatic patients lacking apparent risk factors of hepatic injury.