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Rodrigo Almeida-Paes, Manoel Marques Evangelista Oliveira, Dayvison Francis Saraiva Freitas, Antônio Carlos Francesconi do Valle, Maria Clara Gutierrez-Galhardo, Rosely Maria Zancopé-Oliveira
Sporotrichosis is a subacute to chronic infection caused by members of the Sporothrix schenckii complex. Itraconazole is the first choice antifungal drug for treating this infection, with terbinafine and potassium iodide as alternatives and amphotericin B used in cases of severe infections. Correlation of antifungal susceptibility data with the clinical outcome of the patients is scarce. The aim of this study was to correlate clinical and mycological data in patients with refractory sporotrichosis. In this work, antifungal susceptibilities, determined according to the reference M38-A2 CLSI protocol, of 25 Sporothrix strains, isolated from seven human cases of sporotrichosis with adversities in the treatment, are presented...
October 22, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Jennifer Snaith, Kharis Burns, Jen Kok, Sharon Chen, N Wah Cheung
We document the first case of haematogenous cerebral spread in Rhizopus arrhizus rhino-orbital mucormycosis, and of posaconazole related adrenal insufficiency. A patient presenting with diabetic ketoacidosis and sinusitis was treated with right medial maxillectomy, ethmoidectomy and IV liposomal amphotericin. Orbital exenteration was performed after intraorbital spread of infection. IV caspofungin and posaconazole was added but complicated by adrenal insufficiency. MRI revealed a new left lentiform nucleus and thalamus rim-enhancing lesion indicating haematogenous cerebral spread...
September 2016: Medical Mycology Case Reports
Adela Martin-Vicente, Javier Capilla, Josep Guarro
Clinical and experimental data have shown discrepancies on the efficacy of combinations between triazoles and echinocandins. In this study, anidulafungin plus posaconazole have shown efficacy against a murine systemic infection by three strains of Aspergillus fumigatus The combination increased mice survival and reduced burden in the kidneys over the corresponding monotherapies and voriconazole. Clearance of kidneys was observed in 62% to 100% of animals (strain dependant). We observed good in vitro- in vivo correlation when a cutoff < 1 was indicative of synergy...
October 19, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
João Paulo Zen Siqueira, Deanna A Sutton, Dania García, Josepa Gené, Pamela Thomson, Nathan Wiederhold, Josep Guarro
Aspergillus section Versicolores includes species of clinical relevance and many others that have been poorly studied but are occasionally found in clinical samples. The aim of this study was to investigate, using a multilocus phylogenetic approach, the spectrum of species of the section Versicolores and to determine their in vitro antifungal susceptibility. The study was based on a set of 77 clinical isolates from different USA medical centres, which had been previously identified as belonging to this section...
November 2016: Fungal Biology
Alexandros Kourentas, Maria Vertzoni, Mira Symillides, Bart Hens, Joachim Brouwers, Patrick Augustijns, Christos Reppas
Biorelevant Gastrointestinal Transfer system (BioGIT) has been shown to be useful in reproducing concentrations of drugs in the fasted upper small intestine after their administration in the stomach. In the present investigation, we evaluated the impact of gastrointestinal transfer on luminal performance of commercially available products of two highly lipophilic weak bases, posaconazole (Noxafil(®) suspension) and itraconazole (Sporanox(®) hard gelatin capsules and Sporanox(®) oral solution) by comparing % solid fraction, concentrations and supersaturation in the duodenal compartment of BioGIT with recently reported data in the upper small intestine of healthy adults...
October 9, 2016: International Journal of Pharmaceutics
Daisuke Hagiwara, Akira Watanabe, Katsuhiko Kamei, Gustavo H Goldman
Invasive aspergillosis is a life-threatening mycosis caused by the pathogenic fungus Aspergillus. The predominant causal species is Aspergillus fumigatus, and azole drugs are the treatment of choice. Azole drugs approved for clinical use include itraconazole, voriconazole, posaconazole, and the recently added isavuconazole. However, epidemiological research has indicated that the prevalence of azole-resistant A. fumigatus isolates has increased significantly over the last decade. What is worse is that azole-resistant strains are likely to have emerged not only in response to long-term drug treatment but also because of exposure to azole fungicides in the environment...
2016: Frontiers in Microbiology
Michaela Döring, Karin Melanie Cabanillas Stanchi, Hartwig Klinker, Melinda Eikemeier, Judith Feucht, Franziska Blaeschke, Carl-Philipp Schwarze, Martin Ebinger, Tobias Feuchtinger, Rupert Handgretinger, Werner J Heinz
Invasive fungal infections are one of the major complications in pediatric patients during prolonged neutropenia after chemotherapy. Evaluation of the efficacy and safety of the triazole posaconazole in these patients is missing. This multicenter survey analyzed trough concentrations of 33 pediatric patients with a median age of 8 years during 108 neutropenic episodes who received prophylactic posaconazole oral suspension. A total of 172 posaconazole trough levels were determined to median 438 ng/ml (range 111-2011 ng/ml; mean 468 ± 244 ng/ml)...
October 4, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Soraya Eugenia Morales-López, Constanza G Taverna, María Eugenia Bosco-Borgeat, Ivana Maldonado, Walter Vivot, Wanda Szusz, Guillermo Garcia-Effron, Susana B Córdoba
The presence of the cryptic species belonging to the Candida glabrata complex has not been studied in Argentina. We analyzed a collection of 117 clinical isolates of C. glabrata complex belonging to a National Culture Collection of Instituto Nacional de Microbiología "Dr. Carlos G. Malbrán" from Argentina (40 isolates from blood samples, 18 from other normally sterile sites, 20 from vagina, 14 from urine, 7 from oral cavity, 3 from catheter, 1 from a stool sample and 14 isolates whose clinical origin was not recorded)...
September 28, 2016: Mycopathologia
Elham Rezazadeh, Azar Sabokbar, Maryam Moazeni, Mohammad Sadegh Rezai, Hamid Badali
BACKGROUND: Candida species, as opportunistic organisms, can cause various clinical manifestations, ranging from mild cutaneous infections to systemic candidiasis in otherwise healthy individuals. Remarkably, the incidence and mortality rates of candidemia have significantly increased worldwide, even after advances in medical interventions and the development of novel antifungal drugs. OBJECTIVES: Given the possible resistance to antifungal agents, susceptibility testing can be useful in defining the activity spectrum of antifungals and determining the appropriate treatment regime...
July 2016: Jundishapur Journal of Microbiology
Andrea G Varon, Simone A Nouér, Gloria Barreiros, Beatriz Moritz Trope, Tiyomi Akiti, Marcio Nucci
Hematologic patients with superficial skin lesions on admission growing Fusarium spp. are at high risk to develop invasive fusariosis during neutropenia. We evaluated the impact of primary prophylaxis with a mold-active azole in preventing the occurrence of invasive fusariosis in these patients. From August 2008 to December 2014, patients with acute leukemia, aplastic anemia, or recipients of hematopoietic cell transplantation were screened on admission with dermatologic examination and direct exam and fungal culture of superficial skin lesions...
September 26, 2016: Antimicrobial Agents and Chemotherapy
Duhita G Sant, Santosh G Tupe, Chepuri V Ramana, Mukund V Deshpande
Increase in invasive fungal infections over past few years especially in immunocompromised patients prompted the search for new antifungal agents with improved efficacy. Current antifungal armory includes very few effective drugs like Amphotericin B, new generation azoles including voriconazole and posaconazole, echinocandins like caspofungin, micafungin, to name a few. Azole class of antifungals which target fungal cell membrane are first choice of treatment for many years because of their effectiveness. As fungal cell membrane is predominantly made up of sterols, glycerophospholipids and sphingolipids, the role of lipids in pathogenesis and target identification for improved therapeutics were largely pursued by researchers during last few years...
September 26, 2016: Journal of Applied Microbiology
Alessandro Busca, Anna Candoni, Ernesta Audisio, Roberto Passera, Benedetto Bruno, Federico Monaco, Nicola Mordini, Adriana Vacca, Mario Delia, Franco Aversa, Livio Pagano
Patients with acute myeloid leukemia (AML) during induction chemotherapy and those who receive allogeneic hematopoietic stem cell transplantation (HSCT) are at higher risk of invasive fungal infections (IFI). In the present study, we investigated whether the risk of IFI in AML patients receiving HSCT might be affected by the antifungal prophylaxis with posaconazole administered during the induction/salvage chemotherapy treatment. Between August 2001 and April 2015, 130 patients with AML received itraconazole/fluconazole (group A) and 99 received posaconazole (group B) as antifungal prophylaxis after induction/salvage chemotherapy at 7 Italian centers and all patients received fluconazole as antifungal prophylaxis after HSCT...
September 22, 2016: Biology of Blood and Marrow Transplantation
Marut Tangwattanachuleeporn, Nanthakan Minarin, Saranya Saichan, Pornsuda Sermsri, Ruthairat Mitkornburee, Uwe Groß, Ariya Chindamporn, Oliver Bader
Occurrence of azole-resistant Aspergillus fumigatus (ARAF) in the environment is an emerging problem worldwide, likely impacting on patient treatment. Several resistance mutations are thought to have initially arisen through triazole-based fungicide use in agriculture and subsequently being propagated in a similar manner. Here we investigated the prevalence of ARAF in the environment of Thailand and characterized their susceptibility profiles toward clinically used azole compounds along with underlying resistance mutations...
September 24, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Diego H Cáceres, Juan David Zapata, Sinar D Granada, Luz E Cano, Tonny W Naranjo
BACKGROUND: Colombia currently does not have a specialised service for measuring antifungal levels in serum, which is of prime importance for the proper treatment and correct management of invasive fungal infections. AIMS: To standardise and validate a simple, sensitive, and specific protocol, based on high performance liquid chromatography, complying with the parameters recommended by the Food and Drug Administration, to detect, identify, and quantify serum concentrations of posaconazole...
September 20, 2016: Revista Iberoamericana de Micología
Alessandro Busca, Livio Pagano
Invasive fungal infections (IFI) represent a major hindrance to the success of hematopoietic stem cell transplantation (HSCT), contributing substantially to morbidity and infection-related mortality. During the most recent years several reports indicate an overall increase of IFI among hematologic patients, in particular, invasive aspergillosis, that may be explained, at least partially, by the fact that diagnoses only suspected in the past, are now more easily established due to the application of serum biomarkers and early use of CT scan...
2016: Mediterranean Journal of Hematology and Infectious Diseases
Monica Cal, Jean-Robert Ioset, Matthia A Fügi, Pascal Mäser, Marcel Kaiser
Total clearance of the T. cruzi infection - referred to herein as "sterile cure" - seems to be a critical prerequisite for new drug candidates for Chagas disease, ensuring long-term beneficial effects for patients in the chronic indeterminate stage. This requirement is notably supported by the recent findings of clinical studies involving posaconazole and fosravuconazole, where the majority of patients treated eventually relapsed after an apparent clearance of parasitaemia at the end of treatment. We have adapted an in vitro system to predict the ability of a compound to deliver sterile cure...
August 26, 2016: International Journal for Parasitology, Drugs and Drug Resistance
Anne Mette Dybro, Per Damkier, Torsten Bloch Rasmussen, Maja Hellfritzsch
A 47-year-old woman had been treated with high-dose simvastatin for several years. After systemic treatment with the antifungal agent itraconazole, she developed muscle pain and highly elevated levels of creatine kinase and myoglobin. Muscle biopsy was compatible with statin-associated rhabdomyolysis, probably caused by a drug-drug interaction between simvastatin and itraconazole. The patient made full recovery. Three commonly used statins-simvastatin, atorvastatin and lovastatin-are metabolised by the liver enzyme CYP3A4...
2016: BMJ Case Reports
Aaron N Pham, Joseph S Bubalo, James S Lewis
We describe our experience using the posaconazole delayed-release tablet formulation 400 mg once daily dosing in 20 hematologic malignancy or hematopoietic stem cell transplant patients who were unable to attain pre-specified target minimum serum (trough) concentrations for invasive fungal infection treatment or prophylaxis. The higher dose allowed the majority of patients to achieve pre-specified target trough concentrations without incurring additional toxicities.
September 6, 2016: Antimicrobial Agents and Chemotherapy
Martha F Mushi, Gustave Buname, Oliver Bader, Uwe Groß, Stephen E Mshana
BACKGROUND: Suppurative otitis media (SOM) is a major public health concern worldwide and is associated with increased morbidity. Cases of fungal suppurative otitis media were studied to establish the effect of fungi in otitis media. METHODS: Ear swabs from 410 patients were collected aseptically using sterile cotton swabs from discharging ear through perforated tympanic membrane. Swabs were subjected to microscopic and culture investigations. The species of fungal growing on Sabouraud's agar were identified using MALDI-TOF MS...
2016: BMC Infectious Diseases
Christian Steuer, Andreas R Huber, Luca Bernasconi
BACKGROUND: As LC-MS/MS techniques are becoming more accessible even outside of highly specialized clinical laboratories, pre-analytical issues such as drug stability during specimen storage should be critically evaluated before implementing therapeutic drug monitoring. Our study investigated the influence of physico-chemical properties of different drugs in regard to their interaction with gel separators used in commercial available collection tubes. METHODS: Drug spiked blood samples were analyzed after storage in different commercial gel- and non-gel based serum tubes...
November 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
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