Aspergillosis
Meera Chand, John Holton in Case Studies in Infection Control, 2018
Regarding invasive pulmonary aspergillosis, which of the following are true? Most cases are caused by Aspergillus flavus.Voriconazole is the first choice antifungal therapy.Diagnosis can only be made on the basis of positive culture.A positive culture of Aspergillus from bronchiolar lavage always indicates infection.It is more likely in a patient with HIV who takes antiretrovirals and whose CD4 count is 450 than in a patient taking 20 mg prednisolone each day as part of their rheumatoid arthritis treatment.
Newer antifungal agents in pediatrics
Mahmoud A. Ghannoum, John R. Perfect in Antifungal Therapy, 2019
Voriconazole is available in IV, oral tablet, and oral suspension formulations. In adults, its oral bioavailability is greater than 90%; however, its oral bioavailability is more modest in children, ranging from 44%–65% [4,5]. Pharmacokinetic modeling suggests that this difference can be accounted for by intestinal first pass metabolism occurring in children but not adults [6]. Voriconazole is extensively distributed to tissues, including the CNS, and has been used successfully to treat CNS fungal infections [7,8]. Voriconazole undergoes extensive hepatic metabolism by the cytochrome P450 system and dose adjustment is recommended in individuals with hepatic impairment. High inter-patient variability has been observed in voriconazole drug concentrations over a range of doses and coincides in part with genetic polymorphisms in the CYP enzymes [9]. As a result of genetic polymorphisms in the gene encoding Cyp2C19, some individuals are poor metabolizers, and some are extensive metabolizers [10]. About 5% of white people and 15%–20% of non-Indian Asians have a slow metabolizer phenotype.
Antifungals
Sarah H. Wakelin, Howard I. Maibach, Clive B. Archer in Handbook of Systemic Drug Treatment in Dermatology, 2015
Most imidazole antifungal drugs are only formulated for topical use (clotrimazole, miconazole, econazole) to treat the skin and nails. Ketoconazole is the exception, but is no longer recommended for systemic use due to the risk of hepatotoxicity. Triazoles (itraconazole, fluconazole, voriconazole, posaconazole) are used systemically and have a higher specificity against fungal cytochrome P450 (CYP450) than imidazoles and less human toxicity. Fluconazole has good activity against fungal yeast forms but lacks activity against moulds, whereas itraconazole has a wider spectrum of action, but less reliable bioavailability. Vorioconazole and posaconazole are used for invasive fungal infections. The adverse effects of voriconazole include hepatitis, hair loss, nail changes, phototoxicity and squamous cell carcinoma.
Topically applied 1% voriconazole induces dysplastic changes on the ocular surface: animal study
Published in Cutaneous and Ocular Toxicology, 2018
Gul Arikan, Ezgi Karatas, Banu Lebe, Ziya Ayhan, Canan Asli Utine, Oya Eren Kutsoylu, Uzeyir Gunenc, Osman Yilmaz
Voriconazole is a second-generation antifungal agent having broad spectrum activity and less toxicity compared to other antifungals. It can be used as a first line therapy to treat many fungal infections related to eye both topically and systemically. However, voriconazole eye drop preparation is not commercially avaliable in our country. So voriconazole eye drops are manufactured by diluting the intravenous formulation of 200 mg lyophilized voriconazole powder to get a solution at a concentration of 10 mg/mL (1%). In the management of fungal keratitis, voriconazole eye drops are typically administered with a dosing frequency of one drop every 0.5, 1.0 or 2.0 h initially and then tapered in time depending on the clinical condition. Length of therapy vary widely and may be as long as a year. As the aim of our study was not to treat any fungal infection, but only to expose the ocular surface to the voriconazole eye drop, the experiment was scheduled in noninflamed healthy eyes. In this experimental study voriconazole eye drops were administered 17 times a day for two months.
The effect of topical voriconazole on conjunctiva in rats as revealed by histopathology and immunohistochemistry
Published in Journal of Chemotherapy, 2019
Cumali Degirmenci, Melis Palamar, Hüseyin Aktug, Gürkan Yigittürk, Ali Veral, Ayşe Yagcı
Voriconazole has been used efficiently for the prophylaxis and treatment of fungal infections after the approval of Food and Drug Administration in 2002. Though voriconazole is an effective drug in the treatment of serious fungal infections, there are important adverse effects and risks including visual disturbances such as abnormal vision, colour vision change and photophobia (30%), hepatic enzyme abnormalities (13.4%), photosensitivity and skin reactions (6%).8,17 All these adverse effects are reversible with drug discontinuation. Recently, several reports claimed skin squamous neoplasia as a side effect of voriconazole treatment.5,6 Duration of voriconazole treatment was revealed as a risk factor for squamous neoplasia. However, the mechanism of the development of squamous neoplasia is not clear. In addition, Palamar et al.11 reported a case of squamous neoplasia of the conjunctiva under topical 1% voriconazole treatment, and to our knowledge that report was the first for topical voriconazole use. Also Arıkan et al.18 demonstrated a relationship between topical adminisration of voriconazole and ocular surface dysplasia. This experimental study was designed to demonstrate the effects of voriconazole on conjunctiva by impression cytology, histopathology and immunohistochemistry.
An Observational Study of the Efficacy and Safety of Voriconazole in a Real-Life Clinical Setting
Published in Journal of Chemotherapy, 2019
Sara Blanco-Dorado, Cristina Cea-Arestin, Alba González Carballo, Ana Latorre-Pellicer, Olalla Maroñas Amigo, Gema Barbeito Castiñeiras, María Luisa Pérez del Molino Bernal, Manuel Campos-Toimil, Anxo Fernández-Ferreiro, María J. Lamas
The number of drugs available has recently increased. However, therapeutic success in managing these infections remains a challenge.9 Voriconazole is an effective broad-spectrum antifungal agent with potent activity against significant pathogens, including species of the genus Aspergillus, Candida, Fusarium and Scedosporium.10–12 Voriconazole is available in oral and intravenous formulations. The intravenous formulation is solubilized in sulfobutyl ether beta-cyclodextrin (SBECD). The SBECD vehicle present in the intravenous formulation may accumulate in renally impaired patients and studies in animals indicate that accumulation of SBECD can result in renal toxicities as a result of massive cytoplasmic vacuolation. Available data in humans with impaired renal function and those undergoing renal replacement therapies also indicates an accumulation of SBECD, but toxic effects have not been observed.13–16 Given the uncertainty in its safety, intravenous voriconazole should be avoided when creatinine clearance is less than 50 ml/min.10 Adverse events of voriconazole treatment include liver enzyme abnormalities, skin reactions, hallucinations or confusion and visual disturbances. Azole therapy has been associated with QTc prolongation; for this reason, it should be used with caution in patients with proarrhythmic conditions.17–20
Related Knowledge Centers
- Antifungal
- Aspergillosis
- Candidiasis
- Fungal Infection
- Fusarium
- Histoplasmosis
- Coccidioidomycosis
- Talaromycosis
- Oral Administration
- Intravenous Therapy