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Islam Ghazi, Yukihiro Hamada, David P Nicolau
PURPOSE: The physical compatibility of commonly used agents that could be coadministered in the clinical setting with tedizolid phosphate during Y-site administration was evaluated. METHODS: Tedizolid phosphate vials were reconstituted to a final concentration of 0.8 mg/mL. All other drugs were prepared according to manufacturers' recommendations and diluted with 0.9% sodium chloride injection (where applicable) to the highest standard concentrations used clinically...
November 1, 2016: American Journal of Health-system Pharmacy: AJHP
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
Anna Prigitano, Caterina Cavanna, Marco Passera, Cristina Ossi, Eugenio Sala, Gianluigi Lombardi, Anna Grancini, Concetta De Luca, Simone Bramati, Marina Gelmi, Milvana Tejada, Romualdo Grande, Claudio Farina, Fabiola Lallitto, Anna Maria Tortorano
PURPOSE: The aim of this study was to monitor recent changes in the epidemiology of candidemia and in the antifungal susceptibility profiles of Candida isolates in one Italian region (Lombardy) in 2014-2015 in comparison with two other studies performed in the same area in 1997-1999 and in 2009. METHODS: A laboratory-based surveillance was conducted in 11 microbiology laboratories. Identification of Candida isolates from 868 episodes and antifungal susceptibility testing (YeastOne) was performed locally...
October 17, 2016: Infection
Pedro Llinares, Isabel Ruiz, Rafael Zaragoza, Ricard Ferrer, Alejandro H Rodríguez, Emilio Maseda, Santiago Grau
BACKGROUND: Although in the past decade the management of invasive fungal infections has improved, a number of controversies persist regarding empirical antifungal treatment in critically-ill hematology patients. AIMS: To identify key clinical knowledge to elaborate a set of recommendations, with a high level of consensus, necessary for the approach to fungal infections in critically-ill hematology patients. METHODS: A Spanish prospective questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists in fungal invasive infections from six scientific national societies; intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases...
October 14, 2016: Revista Iberoamericana de Micología
He Wang, Ying-Chun Xu, Po-Ren Hsueh
In the Asia-Pacific region, Candida albicans is the predominant Candida species causing invasive candidiasis/candidemia in Australia, Japan, Korea, Hong Kong, Malaysia, Singapore and Thailand whereas C. tropicalis is the most frequently encountered Candida species in Pakistan and India. Invasive isolates of C. albicans, C. parapsilosis complex and C. tropicalis remain highly susceptible to fluconazole (>90% susceptible). Fluconazole resistance (6.8-15%), isolates with the non-wild-type phenotype for itraconazole susceptibility (3...
October 18, 2016: Future Microbiology
Jinru Zhang, Nicholas Liu, Ralph A Cacho, Zhou Gong, Zhu Liu, Wenming Qin, Chun Tang, Yi Tang, Jiahai Zhou
Nonribosomal peptide synthetases (NRPSs) in fungi biosynthesize important pharmaceutical compounds, including penicillin, cyclosporine and echinocandin. To understand the fungal strategy of forging the macrocyclic peptide linkage, we determined the crystal structures of the terminal condensation-like (CT) domain and the holo thiolation (T)-CT complex of Penicillium aethiopicum TqaA. The first, to our knowledge, structural depiction of the terminal module in a fungal NRPS provides a molecular blueprint for generating new macrocyclic peptide natural products...
October 17, 2016: Nature Chemical Biology
Philippe Montravers, Pierre-François Perrigault, Jean-François Timsit, Jean-Paul Mira, Olivier Lortholary, Olivier Leroy, Jean-Pierre Gangneux, Didier Guillemot, Caroline Bensoussan, Sébastien Bailly, Elie Azoulay, Jean-Michel Constantin, Hervé Dupont
OBJECTIVE: To compare the clinical characteristics and prognosis of patients treated for Candida peritonitis (CP), according to the type of systemic anti-fungal therapy (SAT), empiric (EAF) or targeted (TAF) therapies, and the final diagnosis of infection. METHODS: ICU patients treated for CP were selected among the AmarCAND2 cohort, to compare patients receiving EAF for not confirmed suspicion of CP (EAF/nonCP), to those with suspected secondarily confirmed CP (EAF/CP), or with primarily proven CP receiving TAF...
October 13, 2016: Clinical Microbiology and Infection
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
Sumanun Suwunnakorn, Hironao Wakabayashi, Elena Rustchenko
Candida albicans is an important fungal pathogen with a diploid genome that can adapt to caspofungin, a major drug from the echinocandin class, by a reversible loss of one copy of chromosome 5 (Ch5). Here we explore a hypothesis that more than one gene for negative regulation of echinocandin tolerance is carried on Ch5. We constructed C. albicans strains that each lacked one of the following Ch5 genes: CHT2 for chitinase; PGA4 for glucanosyltransferase, and CSU51, a putative transcription factor. We demonstrate that independent deletion of each of these genes increased caspofungin and anidulafungin, another echinocandin, tolerance...
October 10, 2016: Antimicrobial Agents and Chemotherapy
Francieli Chassot, Tarcieli Pozzebon Venturini, Fernanda Baldissera Piasentin, Janio Morais Santurio, Terezinha Inez Estivalet Svidzinski, Sydney Hartz Alves
We evaluated the in vitro antifungal activity of diphenyl diselenide and ebselen against echinocandin-susceptible and -resistant strains of Candida parapsilosis using the broth microdilution method. Diphenyl diselenide (MIC range=1-8μg/mL) and ebselen (MIC range=0.25-4μg/mL) showed in vitro activity against echinocandin-susceptible isolates. However, ebselen also showed the highest antifungal activity against echinocandin-resistant strains (MIC range=0.06-4μg/mL). This study demonstrated that the antifungal potential of diphenyl diselenide and ebselen deserves further investigation using in vivo experimental protocols...
September 13, 2016: New Microbiologica
Andrée F Maheux, Adnane Sellam, Yves Piché, Maurice Boissinot, René Pelletier, Dominique K Boudreau, François J Picard, Hélène Trépanier, Marie-Josée Boily, Marc Ouellette, Paul H Roy, Michel G Bergeron
Successful treatment of a Candida infection relies on 1) an accurate identification of the pathogenic fungus and 2) on its susceptibility to antifungal drugs. In the present study we investigated the level of correlation between phylogenetical evolution and susceptibility of pathogenic Candida spp. to antifungal drugs. For this, we compared a phylogenetic tree, assembled with the concatenated sequences (2475-bp) of the ATP2, TEF1, and TUF1 genes from 20 representative Candida species, with published minimal inhibitory concentrations (MIC) of the four principal antifungal drug classes commonly used in the treatment of candidiasis: polyenes, triazoles, nucleoside analogues, and echinocandins...
October 3, 2016: Journal of Microbiological Methods
Fabio Araujo Motta, Libera Maria Dalla-Costa, Marisol Dominguez Muro, Mariana Nadal Cardoso, Gledson Luiz Picharski, Gregory Jaeger, Marion Burger
OBJECTIVE: To evaluate risk factors associated with death due to bloodstream infection caused by Candida spp. in pediatric patients and evaluate the resistance to the main anti-fungal used in clinical practice. METHODS: This is a cross-sectional, observational, analytical study with retrospective collection that included 65 hospitalized pediatric patients with bloodstream infection by Candida spp. A univariate analysis was performed to estimate the association between the characteristics of the candidemia patients and death...
October 3, 2016: Jornal de Pediatria
Wolfgang Hüttel
Echinocandins are an important group of cyclic non-ribosomal peptides with strong antifungal activity produced by filamentous fungi from Aspergillaceae and Leotiomycetes. Their structure is characterized by numerous hydroxylated non-proteinogenic amino acids. Biosynthetic clusters discovered in the last years contain up to six oxygenases, all of which are involved in amino acid modifications. Especially, variations in the oxidation pattern induced by these enzymes account for a remarkable structural diversity among the echinocandins...
October 5, 2016: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
Rasmus Hare Jensen
Antifungal drug resistance is a multifaceted clinical challenge, and when present, a primary cause of treatment failure in patients with severe fungal infections. Changing epidemiology, increasing resistance rates and a narrow antifungal armamentarium may further underline the required attention on resistance particularly within the most prevalent invasive fungal infections caused by Candida yeasts and Aspergillus moulds. In Denmark, the resistance epidemiology remains to be fully elucidated. This thesis sought to address this demand as well as provide insight into the landscape of underlying molecular resistance mechanisms...
October 2016: Danish Medical Journal
Elizabeth J Polvi, Anna F Averette, Soo Chan Lee, Taeyup Kim, Yong-Sun Bahn, Amanda O Veri, Nicole Robbins, Joseph Heitman, Leah E Cowen
Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health...
October 2016: PLoS Genetics
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
Cristina Rueda, Mireia Puig-Asensio, Jesús Guinea, Benito Almirante, Manuel Cuenca-Estrella, Oscar Zaragoza
OBJECTIVES: Paradoxical growth (PG) and trailing effect (TE) are frequently observed during antifungal susceptibility testing (AFST). These two phenomena interfere with the determination of the Minimal Inhibitory Concentration (MIC). The aim of this study was to assess the clinical impact of TE and PG. MATERIAL AND METHODS: We analysed the frequency of TE and PG of 690 Candida isolates collected from a population-based study performed in Spain (CANDIPOP) and correlated the results clinical outcome of the patients...
September 24, 2016: Clinical Microbiology and Infection
Costanza Furlanetto, Sonia Merluzzi, Stefano Palcic
Biofilms pose a serious problem for public health. Penetration of pharmacological agents within a biofilm is hampered by the morphological structure of such microbial communities. A biofilm infection therefore entails adverse outcomes both in the field of cost management and patient prognosis. The problem is further complicated if the drugs available to combat a biofilm-related fungal infection versus a bacterial one are compared: in the case of a fungal infection, the drugs available are less efficacious than antibiotics used to counteract a bacterial infection...
September 1, 2016: Le Infezioni in Medicina
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
Taissa Vila, Kelly Ishida, Sergio Henrique Seabra, Sonia Rozental
Candida spp. can adhere to and form biofilms over different surfaces, becoming less susceptible to antifungal treatment. Resistance of biofilms to antifungal agents is multifactorial and the extracellular matrix (ECM) appears to play an important role. Among the few available antifungals for treatment of candidaemia, only the lipid formulations of amphotericin B (AmB) and the echinocandins are effective against biofilms. Our group has previously demonstrated that miltefosine has an important effect against Candida albicans biofilms...
September 12, 2016: International Journal of Antimicrobial Agents
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