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Posaconazole

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https://www.readbyqxmd.com/read/28742650/reliable-and-easy-to-use-liquid-chromatography-tandem-mass-spectrometry-method-for-simultaneous-analysis-of-fluconazole-isavuconazole-itraconazole-hydroxy-itraconazole-posaconazole-and-voriconazole-in-human-plasma-and-serum
#1
Carsten Müller, David Gehlen, Cornelia Blaich, Domenik Prozeller, Blasius Liss, Thomas Streichert, Martin H J Wiesen
BACKGROUND: A fast and easy-to-use liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of six triazoles (fluconazole (FLZ), isavuconazole (ISZ), itraconazole (ITZ), hydroxy-itraconazole (OH-ITZ), posaconazole (PSZ), voriconazole (VRZ)) in human plasma and serum was developed and validated for therapeutic drug monitoring (TDM). METHODS: Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation...
July 24, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28739796/multicenter-and-international-study-of-mic-mec-distributions-for-definition-of-epidemiological-cutoff-values-ecvs-for-species-of-sporothrix-identified-by-molecular-methods
#2
A Espinel-Ingroff, D P B Abreu, R Almeida-Paes, R S N Brilhante, A Chakrabarti, A Chowdhary, F Hagen, S Córdoba, G M Gonzalez, N P Govender, J Guarro, E M Johnson, S E Kidd, S A Pereira, A M Rodrigues, S Rozental, M W Szeszs, R Ballesté Alaniz, A Bonifaz, L X Bonfietti, L P Borba-Santos, J Capilla, A L Colombo, M Dolande, M G Isla, M S C Melhem, A C Mesa-Arango, M M E Oliveira, M M Panizo, Z Pires de Camargo, R M Zancope-Oliveira, J F Meis, J Turnidge
Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic Sporothrix species to antifungal agents are based on a collaborative study that evaluated five clinically relevant isolates of Sporothrix schenckii sensu lato and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and Sporothrix species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for these species...
July 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28736936/invasive-fungal-infection-following-chemotherapy-for-acute-myeloid-leukaemia-experience-from-a-developing-country
#3
Anu Korula, Aby Abraham, Fouzia N Abubacker, Auro Viswabandya, Kavitha M Lakshmi, O C Abraham, Priscilla Rupali, George M Varghese, Joy S Michael, Alok Srivastava, Vikram Mathews, Biju George
The incidence of invasive fungal infections (IFI) is believed to be higher in patients with acute myeloid leukaemia (AML) undergoing chemotherapy in non-HEPA-filtered rooms. The aim of this study is to review the incidence of IFI in a large cohort of patients with AML treated at a single centre in India. Two hundred and twenty-two patients with AML treated with either induction chemotherapy or salvage chemotherapy between 2008 and 2013 were studied retrospectively. IFI was defined as per the revised EORTC-MSG criteria...
July 23, 2017: Mycoses
https://www.readbyqxmd.com/read/28722255/drug-drug-interactions-between-triazole-antifungal-agents-used-to-treat-invasive-aspergillosis-and-immunosuppressants-metabolized-by-cytochrome-p450-3a4
#4
REVIEW
Andreas H Groll, Robert Townsend, Amit Desai, Nkechi Azie, Mark Jones, Marc Engelhardt, Anne-Hortense Schmitt-Hoffman, Robert J Brüggemann
Patients undergoing treatment with immunosuppressant drugs following solid organ or hematopoietic stem cell transplantation are at particular risk for development of serious infections such as invasive aspergillosis. Four triazole antifungal drugs, voriconazole, posaconazole, itraconazole, and isavuconazole, are approved to treat invasive aspergillosis either as first- or second-line therapy. All of these agents are inhibitors of cytochrome P450 3A4, which plays a key role in metabolizing immunosuppressant drugs such as cyclosporine, tacrolimus, and sirolimus...
July 19, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28705676/current-antifungal-treatment-of-fusariosis
#5
Abdullah M S Al-Hatmi, Alexandro Bonifaz, Stephane Ranque, G Sybren de Hoog, Paul E Verweij, Jacques F Meis
Fungi of the genus Fusarium are well known as major plant pathogens and soil inhabitants but also cause a broad spectrum of human infections. Fusariosis is the second most common mould infection after aspergillosis and keratitis is the most encountered implantation infection in immunocompetent individuals. Natamycin is active against Fusarium species both in vitro and in vivo, and it is used along with voriconazole as the mainstay of treatment for Fusarium keratitis. Onychomycosis is treated with terbinafine, voriconazole and sometimes itraconazole...
July 10, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28702763/pharmacokinetics-of-antifungal-drugs-practical-implications-for-optimized-treatment-of-patients
#6
REVIEW
Romuald Bellmann, Piotr Smuszkiewicz
INTRODUCTION: Because of the high mortality of invasive fungal infections (IFIs), appropriate exposure to antifungals appears to be crucial for therapeutic efficacy and safety. MATERIALS AND METHODS: This review summarises published pharmacokinetic data on systemically administered antifungals focusing on co-morbidities, target-site penetration, and combination antifungal therapy. CONCLUSIONS AND DISCUSSION: Amphotericin B is eliminated unchanged via urine and faeces...
July 12, 2017: Infection
https://www.readbyqxmd.com/read/28699245/effects-of-intranasally-dosed-posaconazole-on-fungal-load-and-biomarkers-in-aspergillus-fumigatus-infected-immunocompromised-mice
#7
Genki Kimura, Takahiro Nakaoki, Yuki Nishimoto, Yuto Suzuki, Garth Rapeport, Pete Strong, Kazuhiro Ito, Yasuo Kizawa
Although anti-fungal triazoles are dosed orally or systemically for Aspergillus fumigatus infection, systemic adverse events and limited exposure of the lung cavity would make a topical treatment for the lung an attractive option. In this study, we examined the effects of intranasally dosed posaconazole on survival rates and biomarkers in A. fumigatus (itraconazole susceptible: ATCC13073 [Af]; or resistant: NCPF7100 [AfR]) infected, temporarily neutropenic A/J mice. Once daily treatment produced a dose-dependent improvement of survival of Af-infected mice (ED50 : 0...
July 11, 2017: Mycoses
https://www.readbyqxmd.com/read/28694233/comparing-the-safety-and-efficacy-of-voriconazole-versus-posaconazole-in-the-prevention-of-invasive-fungal-infections-in-high-risk-patients-with-hematological-malignancies
#8
Ray Hachem, Andrew Assaf, Yazan Numan, Pankil Shah, Ying Jiang, Anne-Marie Chaftari, Issam I Raad
Invasive fungal infection (IFI) is a leading cause of morbidity and mortality in immunocompromised cancer patients. New triazole-based antifungal agents have been recommended for IFI prophylaxis in these patients. This retrospective study compared the safety and efficacy of voriconazole and posaconazole as prophylaxis in patients with hematological malignancies (HM), who were admitted to The University of Texas MD Anderson Cancer Center between January 2014 and August 2015, and who were started on single antifungal prophylaxis consisting of either voriconazole or posaconazole...
July 7, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28669678/virulence-and-antifungal-therapy-of-murine-disseminated-infection-by-rhodotorula-mucilaginosa
#9
Pamela Thomson, Loida López-Fernández, Josep Guarro, Javier Capilla
Rhodotorula infections have emerged in recent years causing mainly fungemia associated to high mortality. We have evaluated the in vitro activity of nine antifungal drugs against four clinical strains of Rhodotorula mucilaginosa, being amphotericin B, voriconazole and posaconazole the most active compounds. The experimental virulence of this fungus and the efficacy of the three mentioned drugs were evaluated in disseminated infections in neutropenic mice. Infection resulted in a high fungal load in all the organs studied without evident particular tropism...
June 16, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28664030/disseminated-nannizziopsis-obscura-infection-in-a-renal-transplant-patient-the-first-reported-case
#10
Amy Baggott, Hugh McGann, Richard Barton, Jennifer Ratner
This is a presentation of a case of disseminated fungal infection in a renal transplant patient with Nannizziopsis obscura, a species not previously reported as having caused disseminated disease in humans and not previously reported in the UK. The fungus was isolated from a intramuscular collection and from a lymph node. The patient responded well to a course of posaconazole.
September 2017: Medical Mycology Case Reports
https://www.readbyqxmd.com/read/28655098/-primary-antifungal-prophylaxis-with-posaconazole-plays-a-pivotal-role-during-chemotherapy-of-acute-myeloid-leukemia
#11
B F Gong, Y T Liu, G J Zhang, S N Wei, Y Li, K Q Liu, X Y Gong, X L Zhao, S W Qiu, R X Gu, D Lin, H Wei, C L Zhou, B C Liu, Y Wang, Y C Mi, J X Wang
Objective: To evaluate the incidence of invasive fungal infections (IFI) and usage of intravenous antifungal drugs during remission induction chemotherapy in patients with acute myeloid leukemia (AML) under primary antifungal prophylaxis with posaconazole. Methods: Clinical records from newly diagnosed AML patients above 15 years old in one single center from February 2014 to January 2016 were retrospectively reviewed and analyzed, excluding acute promyelocytic leukemia. The incidence of IFI and usage of intravenous antifungal drugs were investigated between control group (not receiving any broad spectrum antifungal prophylaxis) and treatment group (receiving posaconazole as primary prophylaxis)...
June 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28652241/prophylactic-treatment-with-vt-1161-protects-immunosuppressed-mice-from-rhizopus-arrhizus-var-arrhizus-infection
#12
Teclegiorgis Gebremariam, Sondus Alkhazraji, Lin Lin, Nathan P Wiederhold, Edward P Garvey, William J Hoekstra, Robert J Schotzinger, Thomas F Patterson, Scott G Filler, Ashraf S Ibrahim
We compared prophylactic or continuous therapy of the investigational drug VT-1161 to posaconazole in treating murine mucormycosis due to Rhizopus arrhizus var. arrhizus In the prophylaxis studies, only VT-1161 resulted in improved survival and lowered tissue fungal burden of immunosuppressed infected mice. In the continuous therapy, VT-1161 outperformed posaconazole in prolonging mice survival time despite their comparable effect in lowering tissue fungal burden. These results support the further development of VT-1161 against mucormycosis...
June 26, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28651982/design-and-optimization-of-highly-selective-broad-spectrum-fungal-cyp51-inhibitors
#13
Christopher M Yates, Edward P Garvey, Sammy R Shaver, Robert J Schotzinger, William J Hoekstra
While the orally-active azoles such as fluconazole and posaconazole are effective antifungal agents, they potently inhibit a broad range of off-target human cytochrome P450 enzymes (CYPs) leading to various safety issues (e.g., drug-drug interactions, liver, and reproductive toxicities). Recently we described the rationally-designed, antifungal agent VT-1161 that is more selective for fungal CYP51 than related human CYP enzymes such as CYP3A4. Herein, we describe the use of a homology model of Aspergillus fumigatus to design and optimize a novel series of highly selective, broad spectrum fungal CYP51 inhibitors...
August 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28636889/complications-of-hematopoietic-stem-transplantation-fungal-infections
#14
REVIEW
Ali S Omrani, Reem S Almaghrabi
Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk of invasive fungal infections, especially during the early neutropenic phase and severe graft-versus-host disease. Mold-active prophylaxis should be limited to the highest risk groups. Empiric antifungal therapy for HSCT with persistent febrile neutropenia is associated with unacceptable response rates, unnecessary antifungal therapy, increased risk of toxicity, and inflated costs. Empiric therapy should not be a substitute for detailed work up to identify the cause of fever in such patients...
June 13, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28634301/microbial-glycoside-hydrolases-as-antibiofilm-agents-with-cross-kingdom-activity
#15
Brendan D Snarr, Perrin Baker, Natalie C Bamford, Yukiko Sato, Hong Liu, Mélanie Lehoux, Fabrice N Gravelat, Hanna Ostapska, Shane R Baistrocchi, Robert P Cerone, Elan E Filler, Matthew R Parsek, Scott G Filler, P Lynne Howell, Donald C Sheppard
Galactosaminogalactan and Pel are cationic heteropolysaccharides produced by the opportunistic pathogens Aspergillus fumigatus and Pseudomonas aeruginosa, respectively. These exopolysaccharides both contain 1,4-linked N-acetyl-d-galactosamine and play an important role in biofilm formation by these organisms. Proteins containing glycoside hydrolase domains have recently been identified within the biosynthetic pathway of each exopolysaccharide. Recombinant hydrolase domains from these proteins (Sph3h from A...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630247/saksenaea-vasiformis-infection-in-an-immunocompetent-patient-in-rural-australia
#16
Wiktor Teodor Pilch, Ned Kinnear, Derek Barry Hennessey
An 81-year-old man from rural Australia presented with right pretibial cellulitis 7 days after minor trauma against furniture. He failed to improve despite antibiotics and surgical debridement. Subsequent cultures grew the rare fungus Saksenaea vasiformis, which was treated with further surgical debridement, amphotericin B and posaconazole. This was successful and the patient made a full recovery. We present the case and discuss lessons learnt.
June 18, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28630185/in-vivo-biomarker-analysis-of-intranasally-dosed-pc945-a-novel-antifungal-triazole-on-aspergillus-fumigatus-infection-in-immunocompromised-mice
#17
Genki Kimura, Takahiro Nakaoki, Thomas Colley, Garth Rapeport, Pete Strong, Kazuhiro Ito, Yasuo Kizawa
PC945 is a novel triazole optimised for lung delivery and the objective of this study is to determine the effects of intranasally dosed PC945 on Aspergillus fumigatus infection and associated biomarkers in immunocompromised mice. PC945, posaconazole or voriconazole was treated intranasally once daily on days 0 to 3 (early intervention) or days 1 to 3 (late intervention) post-infection in temporarily neutropenic A/J mice infected intranasally with A. fumigatus, and bronchoalveolar lavage fluid (BALF) and serum were collected on day 3...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28620958/a-network-meta-analysis-of-primary-prophylaxis-for-invasive-fungal-infection-in-haematological-patients
#18
REVIEW
L P Leonart, F S Tonin, V L Ferreira, S T S Penteado, A Wiens, F A Motta, R Pontarolo
WHAT IS KNOWN AND OBJECTIVE: Antifungal prophylaxis is an option to reduce the incidence of invasive fungal infection (IFI) in haematological patients. To date, no network meta-analysis (NMA) of high-quality evidence (double-blind randomized controlled trials) has been performed on this subject. This systematic review and NMA aimed to evaluate the safety and efficacy of different antifungal agents used for prophylaxis of IFI in patients with haematological disorders. METHODS: A systematic review was performed according to PRISMA and Cochrane recommendations...
June 15, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28618155/clinical-outcome-of-cystic-fibrosis-patients-colonized-by-scedosporium-species-following-lung-transplantation-a-single-center-15-year-experience
#19
Perrine Parize, Veronique Boussaud, Vianney Poinsignon, Emilie Sitterlé, Francoise Botterel, Sandrine Lefeuvre, Romain Guillemain, Eric Dannaoui, Elaine M Billaud
BACKGROUND: Fungi of the genus Scedosporium are emerging pathogens responsible for severe infections in lung transplant recipients. These infections are associated with poor prognosis and some centers consider now Scedosporium species colonization as a contraindication to lung transplantation (LT) even though no published evidence demonstrates that Scedosporium species colonization is associated with higher morbidity or mortality after LT. METHODS: Here we aim to describe characteristics and outcome of cystic fibrosis (CF) lung transplant recipients colonized with Scedosporium species in a single center over a 15-year period...
June 15, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28608665/comparison-of-plasma-concentrations-of-posaconazole-with-the-oral-suspension-and-tablet-in-korean-patients-with-hematologic-malignancies
#20
Hyeon Jeong Suh, Inho Kim, Joo Youn Cho, Sang In Park, Seo Hyun Yoon, Jeong Ok Lee, Youngil Koh, Kyoung Ho Song, Pyoeng Gyun Choe, Kyung Sang Yu, Eu Suk Kim, Hong Bin Kim, Soo Mee Bang, Nam Joong Kim, Sang Hoon Song, Wan Beom Park, Myoung Don Oh
The posaconazole tablet formulation was developed to have improved bioavailability compared to the oral suspension. Here, we compared posaconazole plasma concentration (PPC) with the posaconazole oral suspension versus the tablet in Korean patients undergoing remission induction chemotherapy for hematologic malignancies. PPC was measured at 3, 8, and 15 days of treatment with the oral suspension (174 patients) or the tablet (40 patients). At all time-points, mean PPC was significantly higher with the tablet compared to the oral suspension...
June 2017: Infection & Chemotherapy
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