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Anidulafungin

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https://www.readbyqxmd.com/read/28180946/new-developments-and-directions-in-the-clinical-application-of-the-echinocandins
#1
REVIEW
C C Chang, M A Slavin, S C-A Chen
The echinocandins-caspofungin, anidulafungin and micafungin-are semi-synthetic cyclic hexapeptide antimicrobial agents with modified N-linked acyl lipid side chains which anchor the compounds to the phospholipid bilayer of the fungal cell membrane, thereby inhibiting synthesis of fungal cell wall glucan. Over the last 10 years, echinocandins have become the first-line antifungal treatment of candidaemia and other forms of invasive candidiasis (IC). Echinocandins are generally well tolerated, but their use is limited by their requirement for daily intravenous dosing, lack of oral formulation and limited spectrum...
February 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28150341/invasive-infections-due-to-saprochaete-and-geotrichum-species-report-of-23-cases-from-the-fungiscope-registry
#2
Luisa Durán Graeff, Danila Seidel, Maria J G T Vehreschild, Axel Hamprecht, Anupma Kindo, Zdenek Racil, Judit Demeter, Sybren De Hoog, Ute Aurbach, Maren Ziegler, Hilmar Wisplinghoff, Oliver A Cornely
Saprochaete and Geotrichum spp. are rare emerging fungi causing invasive fungal diseases in immunosuppressed patients and scarce evidence is available for treatment decisions. Among 505 cases of rare IFD from the FungiScope(™) registry, we identified 23 cases of invasive infections caused by these fungi reported from 10 countries over a 12-year period. All cases were adults and previous chemotherapy with associated neutropenia was the most common co-morbidity. Fungaemia was confirmed in 14 (61%) cases and deep organ involvement included lungs, liver, spleen, central nervous system and kidneys...
February 2, 2017: Mycoses
https://www.readbyqxmd.com/read/28137817/pharmacokinetics-of-the-novel-echinocandin-cd101-in-multiple-animal-species
#3
Voon Ong, Kenneth D James, Steven Smith, B Radha Krishnan
CD101 is a novel semi-synthetic echinocandin with antifungal activity against Candida and Aspergillus spp. The PK of CD101 administered intravenously to mice, rats, dogs, cynomolgus monkeys, and chimpanzees are presented. CD101 consistently exhibited very low clearance, modest volume of distribution, and long half-life across all species tested. In mouse, rat, dog, cynomolgus monkey, and chimpanzee, CD101 clearance [mL/min/kg] was 0.10, 0.47, 0.30, 0.41, and 0.06; Vss [mL/kg] was 206, 1390, not determined, 597, and 400; and t1/2 [h] was 25, 39, 53, 40, and 81, respectively...
January 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28115858/cost-effectiveness-analysis-of-combination-antifungal-therapy-with-voriconazole-and-anidulafungin-versus-voriconazole-monotherapy-for-primary-treatment-of-invasive-aspergillosis-in-spain
#4
Santiago Grau, Jose Ramon Azanza, Isabel Ruiz, Carlos Vallejo, Josep Mensa, Johan Maertens, Werner J Heinz, Jon Andoni Barrueta, Carmen Peral, Francisco Jesús Mesa, Miguel Barrado, Claudie Charbonneau, Darío Rubio-Rodríguez, Carlos Rubio-Terrés
OBJECTIVE: According to a recent randomized, double-blind clinical trial comparing the combination of voriconazole and anidulafungin (VOR+ANI) with VOR monotherapy for invasive aspergillosis (IA) in patients with hematologic disease or with hematopoietic stem cell transplant, mortality was lower after 6 weeks with VOR+ANI than with VOR monotherapy in a post hoc analysis of patients with galactomannan-based IA. The objective of this study was to compare the cost-effectiveness of VOR+ANI with VOR, from the perspective of hospitals in the Spanish National Health System...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/28088767/pharmacokinetic-study-of-anidulafungin-in-icu-patients-with-intra-abdominal-candidiasis
#5
H Dupont, L Massias, B Jung, N Ammenouche, P Montravers
BACKGROUND: Only limited pharmacokinetic data are available for anidulafungin in ICU patients, especially in patients treated for severe intra-abdominal infection (IAI). METHODS: This was a prospective multicentre observational study in ICU patients with suspected yeast IAI. All patients received an intravenous loading dose of 200 mg of anidulafungin, followed by 100 mg/day. Thirteen blood samples were drawn between day 1 and day 5 for pharmacokinetic analysis...
January 14, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28053212/multilocus-phylogeny-and-antifungal-susceptibility-of-aspergillus-section-circumdati-from-clinical-samples-and-description-of-a-pseudosclerotiorum-sp-nov
#6
J P Z Siqueira, D A Sutton, J Gené, D García, N Wiederhold, S W Peterson, J Guarro
A multilocus phylogenetic study was carried out to assess species identity of a set of 34 clinical isolates from Aspergillus section Circumdati from the USA, and to determine their in vitro antifungal susceptibility against eight antifungal drugs. The genetic markers used were ITS, BenA, CaM and RPB2, and the drugs tested were amphotericin B, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, and terbinafine. The most common species sampled was A. westerdijkiae (29.4%), followed by a novel species, which was described here as A...
January 4, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28052853/activity-of-a-long-acting-echinocandin-cd101-and-seven-comparator-antifungal-agents-tested-against-a-global-collection-of-contemporary-invasive-fungal-isolates-in-the-sentry-2014-antifungal-surveillance-program
#7
Michael A Pfaller, Shawn A Messer, Paul R Rhomberg, Mariana Castanheira
The activity of CD101 and comparators was evaluated against 606 invasive fungal isolates collected worldwide during 2014 using the CLSI method. All C. albicans (n=251), C. tropicalis (n=51), C. krusei (n=16), and C. dubliniensis (n=11) were inhibited by ≤0.12 μg/ml of CD101 and were susceptible or wild type to other echinocandins. Five C. glabrata (n=100) displayed CD101 MIC values of 1-4 μg/ml, elevated caspofungin (2->8 μg/ml), anidulafungin (2-4 μg/ml), and micafungin (2-4 μg/ml) MICs, and carried mutations on fks1/fks2 C...
January 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28031205/in-vitro-activity-of-posaconazole-against-talaromyces-marneffei-by-broth-microdilution-and-etest-methods-comparison-to-itraconazole-voriconazole-and-anidulafungin
#8
Susanna K P Lau, George C S Lo, Clare S K Lam, Wang-Ngai Chow, Antonio H Y Ngan, Alan K L Wu, Dominic N C Tsang, Cindy W S Tse, Tak-Lun Que, Bone S F Tang, Patrick C Y Woo
We determined the susceptibilities of 57 Talaromyces marneffei strains to anidulafungin, itraconazole, voriconazole and posaconazole, with MICs of 2-8, 0.002-0.004, 0.016-0.063 and 0.001-0.002 μg/ml by broth microdilution, and >32, ≤0.002-0.008, ≤0.002-0.008 and ≤0.002 μg/ml by Etest respectively at yeast phase; while MICs at mycelial phase for anidulafungin and posaconazole were 1-2 and 0.004-0.063 μg/ml respectively. The results suggest promising activities of posaconazole. Etest can be used for testing of azoles against T...
December 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28011902/ecil-6-guidelines-for-the-treatment-of-invasive-candidiasis-aspergillosis-and-mucormycosis-in-leukemia-and-hematopoietic-stem-cell-transplant-patients
#9
Frederic Tissot, Samir Agrawal, Livio Pagano, Georgios Petrikkos, Andreas H Groll, Anna Skiada, Cornelia Lass-Flörl, Thierry Calandra, Claudio Viscoli, Raoul Herbrecht
The European Conference on Infections in Leukemia (ECIL) provides recommendations for diagnostic strategies and prophylactic, pre-emptive or targeted therapy strategies for various types of infection in patients with hematological malignancies or hematopoietic stem cell transplantation recipients. Meetings are held every two years since 2005 and evidence-based recommendations are elaborated after evaluation of the literature and discussion among specialists of nearly all European countries. In this manuscript, the ECIL group presents the 2015-update of the recommendations for the targeted treatment of invasive candidiasis, aspergillosis and mucormycosis...
December 23, 2016: Haematologica
https://www.readbyqxmd.com/read/27919891/structure-activity-relationships-of-a-series-of-echinocandins-and-the-discovery-of-cd101-a-highly-stable-and-soluble-echinocandin-with-distinctive-pharmacokinetic-properties
#10
Kenneth D James, Christopher P Laudeman, Navdeep B Malkar, Radha Krishnan, Karen Polowy
Echinocandins are a first-line therapy for candidemia and invasive candidiasis. They are generally safe with few drug interactions, but the stability and pharmacokinetic properties of currently approved echinocandins are such that each was developed for daily intravenous infusion. We sought to discover a novel echinocandin with properties that would enable more flexible dosing regimens, alternate routes of delivery, and expanded utility. Derivatives of known echinocandin scaffolds were generated, and an iterative process of design and screening led to the discovery of CD101, a novel echinocandin that has since demonstrated improved chemical stability and pharmacokinetics...
February 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27904738/recent-developments-in-the-management-of-invasive-fungal-infections-in-patients-with-oncohematological-diseases
#11
REVIEW
Markus Ruhnke, Stefan Schwartz
Patients with hematological cancer have a high risk of invasive fungal diseases (IFDs). These infections are mostly life threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other non-Aspergillus molds are increasingly be identified in cases of documented IFDs. Important risk factors are long lasting granulocytopenia with neutrophil counts below 500/μl for more than 10 days or graft-versus-host disease resulting from allogeneic stem-cell transplantation...
December 2016: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/27902377/comparison-of-susceptibility-patterns-using-commercially-available-susceptibility-testing-methods-performed-on-prevalent-candida-spp
#12
COMPARATIVE STUDY
David Cretella, Katie E Barber, S Travis King, Kayla R Stover
The rising rates of invasive fungal infections caused by non-albicans Candida and the increasing emergence of antifungal resistance complicate the management of invasive candidiasis. Accurate and timely antifungal susceptibility testing is critical to targeting antifungal therapy. The purpose of this study was to compare commercially available susceptibility testing methods using prospectively collected Candida isolates. Susceptibility testing was performed on 74 Candida isolates collected from July 2014 to March 2015 using broth microdilution according to the Clinical and Laboratory Standards Institute method, Etest, Vitek 2 (YS-05) and Sensititre...
December 2016: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27872072/pharmacokinetics-of-anidulafungin-in-critically-ill-intensive-care-unit-patients-with-suspected-or-proven-invasive-fungal-infections
#13
R J M Brüggemann, V Middel-Baars, D W de Lange, A Colbers, A R J Girbes, P Pickkers, E L Swart
Echinocandins, such as anidulafungin, are the first-line treatment for candidemia or invasive candidiasis in critically ill patients. There are conflicting data on the pharmacokinetic properties of anidulafungin in intensive care unit (ICU) patients. Adult ICU patients (from 3 hospitals) receiving anidulafungin for suspected or proven fungal infections were included in the present study. Patients were considered evaluable if a pharmacokinetic curve for day 3 could be completed. Twenty-three of 36 patients (7 female and 16 male) were evaluable...
February 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27872063/in-vitro-exposure-to-increasing-micafungin-concentrations-easily-promotes-echinocandin-resistance-in-candida-glabrata-isolates
#14
María Ángeles Bordallo-Cardona, Pilar Escribano, Elia Gómez G de la Pedrosa, Laura Judith Marcos-Zambrano, Rafael Cantón, Emilio Bouza, Jesús Guinea
We assessed the in vitro susceptibility of five echinocandin-susceptible Candida glabrata isolates after exposure to micafungin. The direct exposure to plates at different micafungin concentrations resulted in the inhibition of growth at 0.062 μg/ml. The progressive exposure was performed on plates using 0.031 μg/ml of micafungin and sequential propagation on plates containing the next 2-fold concentration; the MICs of micafungin and anidulafungin increased sequentially, and all the isolates became echinocandin resistant, showing fks2 mutations...
February 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27799221/frequency-of-the-paradoxical-effect-measured-using-the-eucast-procedure-with-micafungin-anidulafungin-and-caspofungin-against-candida-species-isolates-causing-candidemia
#15
Laura Judith Marcos-Zambrano, Pilar Escribano, Carlos Sánchez-Carrillo, Emilio Bouza, Jesús Guinea
We report data on the frequency of the paradoxical effect of echinocandins against Candida spp. (n = 602 incident isolates) using the EUCAST definitive document EDef 7.2 procedure. The paradoxical effect for one or more echinocandins was observed in 16% of the isolates. However, differences between species were found, and the paradoxical effect was more common in Candida tropicalis (P < 0.001). Caspofungin was the drug in which the paradoxical effect was most common, followed by anidulafungin and micafungin (P < 0...
January 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27799206/multicenter-study-of-method-dependent-epidemiological-cutoff-values-for-detection-of-resistance-in-candida-spp-and-aspergillus-spp-to-amphotericin-b-and-echinocandins-for-the-etest-agar-diffusion-method
#16
A Espinel-Ingroff, M Arendrup, E Cantón, S Cordoba, E Dannaoui, J García-Rodríguez, G M Gonzalez, N P Govender, E Martin-Mazuelos, M Lackner, C Lass-Flörl, M J Linares Sicilia, M A Rodriguez-Iglesias, T Pelaez, R K Shields, G Garcia-Effron, J Guinea, M Sanguinetti, J Turnidge
Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C...
January 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27760829/synergistic-effect-of-anidulafungin-combined-with-posaconazole-in-experimental-aspergillosis
#17
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
https://www.readbyqxmd.com/read/27751781/epico-3-0-empirical-antifungal-therapy-in-critically-ill-hematology-patients
#18
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 2016: Revista Iberoamericana de Micología
https://www.readbyqxmd.com/read/27750452/epidemiology-of-candidemia-and-antifungal-susceptibility-in-invasive-candida-species-in-the-asia-pacific-region
#19
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 2016: Future Microbiology
https://www.readbyqxmd.com/read/27746090/-epidemiology-risk-factors-and-in-vitro-susceptibility-in-candidaemia-due-to-non-candida-albicans-species
#20
Elena M Marín Martínez, Ana Isabel Aller García, Estrella Martín-Mazuelos
BACKGROUND: Invasive fungal infection (IFI) has increased in recent years due to there being a greater number of risk factors. IFI caused by Candida is the most frequent, and although Candida albicans is the most isolated species, there is currently a decrease of C. albicans and an increase of other species of the genus. AIMS: To analyse the epidemiology, risk factors, and antifungal susceptibility of blood culture isolates of non-C.albicans Candida species in our hospital in the last 12years...
October 2016: Revista Iberoamericana de Micología
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