Dilek Yeşim Metin

In-situ gel formulations of econazole nitrate: preparation and in-vitro and in-vivo evaluation

Objectives  This study describes the in‐situ gelling of econazole nitrate containing thermosensitive polymers composed of poloxamer 407 and 188 as a novel treatment platform for vaginal candidiasis.

Onychomycosis in primary school children: association with socioeconomic conditions.

Onychomycosis in childhood is reported to be unusual. The aim of this study was to determine the prevalence of onychomycosis in primary school children and to make comparison between different socioeconomic status in the rural and urban areas of the city. Hand and foot nails of 23235 children aged 7–14 were examined. Onychomycosis was suspected and nail scrapings for mycological examination were taken in 116 of them. Hyphae or spores were seen in 41 (0.18%) by direct microscopic examination, and mycological cultures were positive in 24 (0.1%) of them. Toenails were affected in all of the fungal culture positive cases. Trichosporon spp, Trichophyton rubrum, Candida albicans and Candida glabrata grew in 11, 6, 5 and 2 of the cultures repectively. Onychomycosis prevalence was significantly higher in the children living in the rural areas (p = 0.016) [Odds ratio = 3.43 (%95 CI 1.11

The efficacy of two different lipid-based amphotericin B in neonatal Candida septicemia

Abstract Background : Fungal sepsis is becoming more frequent in neonatal intensive care units (NICU) and has a high mortality rate due to the invasive nature of the disease and to the insufficiency of low doses and high incidence of renal problems with effective doses of amphotericin B. New generation lipid formulated amphotericin B preparations may be more efficient because they are less toxic to be applied in target doses. However, there is limited experience in neonates and preterm infants.

Evaluation of Antifungal Susceptibility Testing with Microdilution and Etest Methods of Candida Blood Isolates

Candida species that show an increasing number of clinical and/or microbiological resistance to several antifungals and are the most common agents of invasive fungal infections. The aim of this study was to investigate the in vitro susceptibility of Candida blood isolates to antifungal agents (amphotericin B, fluconazole, itraconazole, and voriconazole) by comparative use of the CLSI reference microdilution method and Etest. Four hundred Candida blood isolates (215 Candidaalbicans, 185 non-albicansCandida strains) were included in the study. The broth microdilution test was performed according to the CLSI M27 A2 document. Etest was carried out according to the manufacturer’s instructions. The MIC results obtained with reference microdilution were compared with those obtained with the Etest by using percent and categorical agreements. According to MIK90 values, voriconazole was the most active and itraconazole was the least active drug in vitro against all Candida species. Other than voriconazole, statistically significant differences were found when the susceptibility of Candida albicans and non-albicans Candida spp. to amphotericin B, fluconazole, and itraconazole were compared. These antifungal agents were found to be more active to C. albicans. Among the non-albicansCandida species, the lowest MIC values were obtained for Candida parapsilosis isolates. When the standard method was compared with Etest, the total agreement was higher for C. albicans than for non-albicans species, especially for fluconazole and voriconazole. In view of the findings, it was concluded that itraconazole showed the lowest activity against all Candida species. Etest could be an alternative method in assessing the in vitro antifungal susceptibility of Candida spp., but it is more convenient to use the microdilution method for studying in vitro susceptibility of non-albicans species, in particular for those possessing high MIC values against azoles.

Terbinafine hydrochloride loaded liposome film formulation for treatment of onychomycosis: in vitro and in vivo evaluation.

Abstract Onychomycosis is a fungal infection of nail unit that is caused by dermatophytes. Oral Terbinafine hydrochloride (TBF-HCl) is being used for the treatment of onychomycosis since 24 years. The side effects caused by the systemic application and limitations of topical administration of this drug regarding the diffusion through nail lead to the development of a new formulation based on, TBF-HCl-loaded liposome. The newly obtained film formulations were prepared and characterized via several parameters, such as physical appearance, drug content, thickness, bioadhesive properties and tensile strength. In vitro and ex vivo permeation studies were performed to select an optimum film formulation for antifungal activity to show the efficiency of formulations regarding the treatment of onychomycosis. The in vitro release percentages of drug were found 71.6 ± 3.28, 54.4 ± 4.26, 56.1 ± 7.48 and 46.0 ± 2.43 for liposome loaded pullulan films (LI-P, LII-P) and liposome loaded Eudragit films (LI-E, LII-E), respectively. The accumulated drug in the nail plates were found 31.16 ± 4.22, 24.81 ± 5.35, 8.17 ± 1.81 and 8.92 ± 3.37 for LI-P, LII-P, LI-E and LII-E, respectively, which within therapeutic range for all film formulations. The accumulated drug in the nail plate was found within therapeutic range for all film formulations. The efficacy of the selected TBF-HCl-loaded liposome film formulation was compared with TBF-HCl-loaded liposome, ethosome, liposome poloxamer gel and ethosome chitosan gel formulations. It was found that TBF-HCl-loaded liposome film formulation had better antifungal activity on fungal nails which make this liposome film formulation promising for ungual therapy of fungal nail infection.

A mucormycosis case presented with orbital apex syndrome and hemiplegia in a renal transplant patient.

Solid organ transplantation is a risk factor for mucormycosis. Mucormycosis is a necrotizing opportunistic fungal infection with high morbidity and mortality. We report a fatal mucormycosis case with rhino-orbital-cerebral involvement in a renal transplant patient, which presented with orbital apex syndrome and hemiplegia.

In Vitro Release—In Vivo Microbiological and Toxicological Studies on Ketoconazole Lipid Granules

In some multidrug therapy programs, ketoconazole (KTZ) may be administered with some antacids that could modify its dissolution rate and reduce its absorption, thus leading to therapeutic failures. The primary aim of this study was to evaluate the influence of Compritol HD5 ATO and Compritol 888 ATO on this interaction in comparison with commercial KTZ tablets. The second aim was to prepare lipid granules of KTZ that could be an alternative to the commercial formulation. Therefore, six KTZ sustained-release granules were prepared with different lipid concentrations, because they were found to be more suitable than tablets that are dissolved only in gastric medium. The results confirmed that the dissolution rate of KTZ granules was significantly reduced in the presence of antacids. The ideal formulation was selected as granules including 5% of Compritol lipids in relation to the suitability of the target profile. Therapeutic effects of orally administered, ideal KTZ granule formulations, and commercial tablets were evaluated in vivo by the experimental model of murine vulvo-vaginal candidiasis (VVC) with and without antacids. It was found that formulations were very effective on VVC, and the therapeutic effect decreased significantly in the presence of antacids. Histopathological studies were carried out for vagina, stomach, and liver tissues and hepatoxicity was also examined. The levels of reduced glutathione (GSH) were measured to assess the oxidative stress induced by KTZ and function of the liver. It was observed that orally administered formulations of KTZ were successful in treating candidiasis in mice without irritancy in stomach. However, liver tissues were damaged. The decreased GSH levels indicated toxicity in our study. This study suggested that in vitro release and in vivo microbiological-toxicological properties of KTZ were affected by antacids and drug-excipient interactions. Lipid granules of KTZ prepared with Compritol 888 ATO could be proposed as a new KTZ solid dosage form with optimum dissolution and therapeutic characteristics.

Skin infection on both legs caused by Acremonium strictum (case report).

Acremonium species are saprophytic molds widely distributed in nature, existing in soil and decaying vegetation. Penetrating wounds, intravascular catheters and immunosuppression are risk factors for invasive infections of Acremonium. The fungus can also cause cutaneous infections and mycetoma in the immunocompetent; such infections occur in extremities open to trauma. In this paper, a female patient with skin infection due to Acremonium strictum in both legs is described.

Effect of Isolation of Candida Species from Respiratory Specimens on Prognosis

Objective: Candida species are often isolated from respiratory specimens of patients with a history of long duration of hospitalization, immunosuppression, diabetes, alcoholism, history of wide spectrum antibiotic or corticosteroid usage. The aim of this retrospective study is to investigate the effect of isolation of Candida species from respiratory specimens on prognosis. Material and Method: Patients in the Department of Chest Disease in whom Candida species had been grown in ≥2 respiratory specimens obtained at the same or at different time periods within the last two years were enrolled in the study. Demographic features of the patients, risk factors for fungal infection, and the effect of this infection on prognosis were evaluated. Results: Out of 47 cases (mean age 67.6±14.6 yrs, 33 males) enrolled in the study, 29 were diagnosed as pneumonia at admission. The most frequent species isolated was C. albicans (68.1%). Fifty bacterial agents were isolated from respiratory specimens of 29 patients (61.7%) initially or on follow-up along with Candida species. Immunosuppression was detected in 28 patients (59.6%). Mean duration of hospitalization was 22.3±15.2 days and 26 patients (55.3%) died. Radiologically, multiple-zone involvement, C. tropicalis isolation, high APACHE II score, co-existing bacterial infection, low PaO 2 /FiO 2 ratio, and low albumin levels were found to be associated with mortality. Conclusion: This study showed that Candida species could also be isolated in respiratory specimens of non-immunosuppressed patients and mortality was high. It was concluded that bacterial co-infection and C. tropicalis isolation affected the prognosis negatively. (Tur Toraks Der 2011; 12: 153-7)