DOCSLIB.ORG

Impact of Infection Status and Cyclosporine on Voriconazole Pharmacokinetics in an Experimental Model of Cerebral Scedosporiosis S

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Impact of Infection Status and Cyclosporine on Voriconazole Pharmacokinetics in an Experimental Model of Cerebral Scedosporiosis S Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/02/28/jpet.117.245449.DC1 1521-0103/365/2/408–412$35.00 https://doi.org/10.1124/jpet.117.245449 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 365:408–412, May 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Impact of Infection Status and Cyclosporine on Voriconazole Pharmacokinetics in an Experimental Model of Cerebral Scedosporiosis s Bénédicte Lelièvre, Marie Briet, Charlotte Godon, Pierre Legras, Jérémie Riou, Patrick Vandeputte, Bertrand Diquet, and Jean-Philippe Bouchara Service de Pharmacologie-Toxicologie-Centre Régional de Pharmacovigilance, Institut de Biologie en Santé (B.L., M.B., B.D.), MITOVASC, UMR CNRS 6214, Inserm 1083, Université d’Angers (M.B.), Micro- et Nanomédecines Biomimétiques, UMR INSERM 1066–CNRS 6021, Université d’Angers (J.R.), and Laboratoire de Parasitologie-Mycologie, Institut de Biologie en Santé ’ (J.-P.B.), Centre Hospitalier Universitaire, Angers, France; Groupe d Etude des Interactions Hôte-Pathogène (EA 3142), Downloaded from Université d’Angers, Université de Bretagne Occidentale, Institut de Biologie en Santé, Angers, France (B.L., C.G., P.L., P.V., J.- P.B., B.D.); and Service Commun de l’Animalerie Hospitalo-Universitaire, Université d’Angers, Angers, France (P.L.) Received October 3, 2017; accepted February 15, 2018 ABSTRACT jpet.aspetjournals.org Cerebral Scedosporium infections usually occur in lung trans- mass spectrometry and high-performance liquid chromatography plant recipients as well as in immunocompetent patients in the UV methods and were documented up to 48 hours after adminis- context of near drowning. Voriconazole is the first-line treatment. tration. Pharmacokinetic parameters were estimated using a non- The diffusion of voriconazole through the blood-brain barrier in compartmental approach. Voriconazole pharmacokinetic profiles the context of cerebral infection and cyclosporine administration were similar for plasma, CSF, and brain in all groups studied. The is crucial and remains a matter of debate. To address this issue, voriconazole Cmax and area under the curve (AUC) (AUC0 $ 48 hours) the pharmacokinetics of voriconazole was assessed in the values were significantly higher inplasmathaninCSF[CSF/plasma plasma, cerebrospinal fluid (CSF), and brain in an experimental ratio, median (range) 5 0.5 (0.39–0.55) for AUC0 $ 48 hours and 0.47 at ASPET Journals on October 1, 2021 model of cerebral scedosporiosis in rats receiving or not re- (0.35 and 0.75) for Cmax]. Cyclosporine administration was signif- ceiving cyclosporine. A single dose of voriconazole (30 mg/kg, icantlyassociatedwithanincreaseinvoriconazoleexposureinthe i.v.) was administered to six groups of rats randomized accord- plasma, CSF, and brain. In the plasma, but not in the brain, an ing to the infection status and the cyclosporine dosing regimen (no interaction between the infection and cyclosporine administration cyclosporine, a single dose, or three doses; 15 mg/kg each). reduced the positive impact of cyclosporine on voriconazole Voriconazole concentrations in plasma, CSF, and brain samples were exposure. Together, these results emphasize the impact of cyclo- quantified using ultra-performance liquid chromatography–tandem sporine on brain voriconazole exposure. Introduction may occur (Morin et al., 1999; Symoens et al., 2006; Morio et al., 2010; Luijk et al., 2011; Miraldi et al., 2012; Hirschi Usually a saprophyte, Scedosporium apiospermum is a et al., 2012). In addition, cerebral scedosporiosis is also filamentous soil fungus that may cause a wide variety of reported in immunocompetent patients in the context of near diseases in human, ranging from localized infections such as drowning (Cortez et al., 2008). Until the 1990s, the mortality subcutaneous mycetoma, keratitis, or bone and joint mycoses rate in systemic S. apiospermum infections was higher than to disseminated infections (Steinbach and Perfect, 2003; 75%; however, recent triazole antifungals have improved their Cortez et al., 2008). This old pathogen has gained increasing prognosis (Steinbach and Perfect, 2003; Cortez et al., 2008). attention during the past two decades due to its worldwide Current recommendations for the management of patients recognition as the second most common cause of fungal with a systemic S. apiospermum infection rely on the use of respiratory infections in patients with cystic fibrosis (Cimon voriconazole (Tortorano et al., 2014). et al., 2000; Rainer et al., 2008; Harun et al., 2010). In this Voriconazole is a triazole drug inhibiting cytochrome context, following lung transplantation in cystic fibrosis P450–dependent 14a-lanosterol demethylase, an enzyme that patients previously colonized by S. apiospermum, severe and plays a key role in the synthesis of ergosterol, which is a major often fatal disseminated infections with cerebral involvement constituent of fungal membranes (Manavathu et al., 1998). Although voriconazole is a broad-spectrum antifungal that acts Financial support for this research was provided by the Association pour la on both yeasts and filamentous fungi, differences occur between Recherche en Pharmacologie et Toxicologie d’Angers (Angers, France). https://doi.org/10.1124/jpet.117.245449. fungal species in their susceptibility to this drug. For in- s This article has supplemental material available at jpet.aspetjournals.org. stance, voriconazole usually exhibits high minimum inhibitory ABBREVIATIONS: AUC, area under the curve; CSF, cerebrospinal fluid. 408 Voriconazole Pharmacokinetics in Experimental Scedosporiosis 409 concentrations against Scedosporium isolates (Sheehan et al., isoflurane for induction (5–10 minutes) and then 2% isoflurane in 1999; Lewis et al., 2005). 20:1 air/oxygen for maintenance. As such, exposure to isoflurane never In humans, the pharmacokinetics of voriconazole follow a exceeded 15 minutes for each rat. nonlinear profile, with 58% of the drug bound to plasma Sampling for Pharmacokinetic Studies. Regarding the intra- proteins (Levêque et al., 2006). The drug is metabolized by venous route of administration and published data, the pharmacoki- cytochrome P450s, mainly CYP3A4, CYP2C19, and to a lesser netics of voriconazole were studied for 48 hours, using eight sampling times: 5 and 20 minutes and 1, 3, 6, 10, 24, and 48 hours after extent CYP2C9 (Purkins et al., 2002). Studies using human administration. Blood samples were collected from three rats for liver microsomes have shown that the metabolism of vorico- each sampling time in EDTAK2-containing tubes (Becton-Dickinson, nazole presents biphasic kinetics (Hyland et al., 2003). The Plymouth, UK) and immediately centrifuged at 3240g for 10 minutes entire dose of voriconazole is eliminated by the renal route in at 15°C. CSF samples were collected at the same time points and 48 hours, mainly (98%) as metabolites (Levêque et al., 2006). immediately centrifuged for 10 minutes at 4°C. Plasma and CSF were Due to the nonlinear pharmacokinetics of voriconazole and immediately frozen and stored at 220°C until analysis. After eutha- intra- and interindividual variability, therapeutic drug mon- nizing the animals, the brains were collected, washed with sodium itoring of voriconazole in plasma is recommended. Neverthe- chloride 0.9%, weighed, and ground in 4 ml of water. The volume of less, very limited pharmacokinetics data are available each homogenate was precisely measured, and three aliquots per 2 regarding infections localized to sanctuary organs such as homogenate were immediately frozen and stored at 20°C. Voriconazole Assay. Voriconazole was quantified in plasma or the brain or lungs. In the case of a cerebral infection, the rate of CSF samples after protein precipitation by ultra-performance liquid diffusion of the antifungal drugs through the blood-brain chromatography–tandem mass spectrometry (Quattro Premier; Wa- Downloaded from barrier remains questionable. ters, Guyancourt, France). Protein precipitation was carried out using In the present study, we determined the pharmacokinetics 200 ml of methanol containing d3-voriconazole as the internal of voriconazole in the plasma, cerebrospinal fluid (CSF), and standard (LGC Standards, Molsheim, France). After homogenization brain in a rat model of disseminated scedosporiosis with and centrifugation, the resulting supernatant was filtered and trans- cerebral involvement to evaluate its diffusion through the ferred to microvials to be analyzed using an Acquity UPLC BEH C18 blood-brain barrier. In addition, the study was designed to Column (1.7 mm, 2.1 Â 50 mm; Waters), maintained at 40°C. The jpet.aspetjournals.org investigate the impact of infection and/or cyclosporine admin- mobile phase was nebulized using an electrospray source in positive . istration on the voriconazole pharmacokinetics in the plasma, mode. The multiple reactions monitoring transitions were m/z 350 127 and 350 . 280.9 for voriconazole and m/z 353 . 130 and 353 . CSF, and brain. 283.9 for d3-voriconazole. The calibration curves were quadratic over the range 0.002–20 mg/l with a coefficient of determination .0.99. Materials and Methods Based on quality control samples, the overall relative S.D. was below 10% (intraday and interday precisions were 7.5% and 5.0%, respec- Animal Model of Scedosporiosis and Study Design. Male tively). The overall relative error was within 610%. The lower limit of at ASPET Journals on October
Load more

Recommended publications
  • Scedosporiosis in a Combined Kidney and Liver Transplant Recipient: a Case Report of Possible Transmission from a Near-Drowning Donor
    Hindawi Publishing Corporation Case Reports in Transplantation Volume 2016, Article ID 1879529, 7 pages http://dx.doi.org/10.1155/2016/1879529 Case Report Scedosporiosis in a Combined Kidney and Liver Transplant Recipient: A Case Report of Possible Transmission from a Near-Drowning Donor Rachael Leek,1 Erika Aldag,1 Iram Nadeem,1 Vikraman Gunabushanam,1 Ajay Sahajpal,1,2 David J. Kramer,2,3 and Thomas J. Walsh4 1 Department of Abdominal Transplant, Aurora St. Luke’s Medical Center, Milwaukee, WI, USA 2University of Wisconsin School of MedicineandPublicHealth,Madison,WI53726,USA 3Department of Critical Care, Aurora St. Luke’s Medical Center, Milwaukee, WI, USA 4Weill Cornell Medicine, Cornell University and New York Presbyterian Hospital, New York, NY, USA Correspondence should be addressed to Erika Aldag; [email protected] Received 29 August 2016; Accepted 6 November 2016 Academic Editor: Graeme Forrest Copyright © 2016 Rachael Leek et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Scedosporium spp. are saprobic fungi that cause serious infections in immunocompromised hosts and in near-drowning victims. Solid organ transplant recipients are at increased risk of scedosporiosis as they require aggressive immunosuppression to prevent allograft rejection. We present a case of disseminated Scedosporium apiospermum infection occurring in the recipient of a combined kidney and liver transplantation whose organs were donated by a near-drowning victim and review the literature of scedosporiosis in solid organ transplantation. 1. Introduction near-drowning events. There are few cases of donor to recipient transmission of infection of Scedosporium spp.
    [Show full text]
  • Pulmonary Scedosporiosis Mimicking Aspergilloma in an Immunocompetent Host: a Case Report and Review of the Literature Fasih Ur Rahman Aga Khan University
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by eCommons@AKU eCommons@AKU Department of Surgery Department of Surgery February 2016 Pulmonary scedosporiosis mimicking aspergilloma in an immunocompetent host: a case report and review of the literature Fasih Ur Rahman Aga Khan University Muhammad Irfan Ul Haq Aga Khan University Naima Fasih Aga Khan University, [email protected] Kauser Jabeen Aga Khan University, [email protected] Follow this and additional works at: http://ecommons.aku.edu/pakistan_fhs_mc_surg_surg Part of the Surgery Commons Recommended Citation Rahman, F., Muhammad Irfan Ul Haq, ., Fasih, N., Jabeen, K. (2016). Pulmonary scedosporiosis mimicking aspergilloma in an immunocompetent host: a case report and review of the literature. Infection, 44(1), 127-132. Available at: http://ecommons.aku.edu/pakistan_fhs_mc_surg_surg/610 Infection (2016) 44:127–132 DOI 10.1007/s15010-015-0840-4 CASE REPORT Pulmonary scedosporiosis mimicking aspergilloma in an immunocompetent host: a case report and review of the literature Fasih Ur Rahman1 · Muhammad Irfan1 · Naima Fasih2 · Kauser Jabeen2 · Hasanat Sharif3 Received: 10 December 2014 / Accepted: 31 August 2015 / Published online: 9 September 2015 © Springer-Verlag Berlin Heidelberg 2015 Abstract A case of localized lung scedosporiosis is Introduction reported here that mimicked aspergilloma in an immu- nocompetent host. Through this case the importance of Scedosporium species is an emergent fungal pathogen asso- considering Scedosporium spp. in differential diagnosis ciated with a wide range of infections ranging, from sub- of locally invasive lung infections and fungal ball is high- cutaneous mycetoma to disseminated sepsis [1]. Localized lighted.
    [Show full text]
  • Scedosporium, Chrysosporium, Sepedonium Ve Beauveria)
    Simpozyum: Hyalen küfler ve hyalohifomikozlar (Aspergillus dışı) TEK KONİDİYUM OLUŞTURAN HYALEN KÜFLER VE İNFEKSİYONLARI (SCEDOSPORIUM, CHRYSOSPORIUM, SEPEDONIUM VE BEAUVERIA) Şaban GÜRCAN Trakya Üniversitesi Tıp Fakültesi, Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dalı, Edirne, ([email protected]) Scedosporium Scedosporium cinsinin tıpta önemli olan ve isimleri birkaç kez değiştirilmiş olan iki türü vardır: Scedosporium apiospermum ve Scedosporium prolificans (1-3). Bunlar esasen immünkompro- mize hastalarda öldürücü pulmoner veya yaygın infeksiyonlara, immünkompetan hastalarda travma, cerrahi uygulama, boğulma veya intravenöz ilaç kullanımını takiben lokalize infeksi- yonlara neden olabilen hifomiçetlerdir (4-6). İnvazif ve yaygın infeksiyonlar organ nakli, lösemi, lenfoma, sistemik lupus eritamatozus veya Crohn Hastalığı için immünsüpresif tedavi veya kortikosteroit alan hastalarda görülür (7-9). Pseudallescheria boydii’nin aseksüel formu olan S. apiospermum tüm dünyada yaygın olarak bulunur ancak olgular daha çok İspanya, Avustralya ve takiben Amerika Birleşik Devletleri’nden bildirilmiştir (6, 7, 10). Genel virulans özellikleri düşük olmasına rağmen diğer saprofitlerle kıyaslandığında Pseudallescheria/ Scedosporium göreceli yüksek virulansa sahiptir (2, 7). Pseudallescheria/Scedosporium türleri toprak, çürüyen bitki, lağım pisliği, kirli su ve çiftlik hayvanlarının gübrelerinden izole edilebilirler (2, 7). İnsanlarda ise kütanöz (miçetom, madura ayağı), solunum sistemi ve santral sinir sistemi infeksiyonları sırasıyla en
    [Show full text]
  • Scedosporium Apiospermum EUMYCETOMA SUCCESSFULLY TREATED with ORAL VORICONAZOLE: REPORT of a CASE and REVIEW of the BRAZILIAN REPORTS on SCEDOSPORIOSIS
    Rev. Inst. Med. Trop. Sao Paulo 55(2):121-123, March-April, 2013 doi: 10.1590/S0036-46652013000200010 Scedosporium apiospermum EUMYCETOMA SUCCESSFULLY TREATED WITH ORAL VORICONAZOLE: REPORT OF A CASE AND REVIEW OF THE BRAZILIAN REPORTS ON SCEDOSPORIOSIS Flávio de Mattos OLIVEIRA(1,2), Gisela UNIS(3,4), Bruno HOCHHEGGER(5) & Luiz Carlos SEVERO(2,6,7) SUMMARY We describe a case of white-grain eumycetoma caused by Scedosporium apiospermum in an immunocompetent host that was successfully treated with oral voriconazole, and we review the Brazilian reports on scedosporiosis. KEYWORDS: Scedosporium apiospermum; Pseudallescheria boydii; Scedosporiosis; Eumycetoma, Voriconazole. INTRODUCTION examination revealed a tumor-like process of the foot that had several draining sinus tracts (Fig. 1). Foot plain radiography showed widening The asexual state of the ascomycete Scedosporium apiospermum of joint spaces, periostial reaction, bone destruction, erosive changes (previously known as Monosporium apiospermum) and its sexual and demineralization (Fig. 2). An incisional skin biopsy was taken from state, Pseudallescheria apiosperma (previously Allescheria boydii, the foot over opening draining sinuses. Haematoxilin and eosin stain Petriellidium boydii and Pseudallescheria boydii), are ubiquitous demonstrated a granulomatous response on the dermis and subcutaneous saprobic fungi commonly found in temperate climates, and have been tissue containing localized abscesses with spherical white-grain recovered from water, sewage, soil, swamps, and manure2,4. Both sexual eumycetoma. Culture of a sample of the biopsy on Sabouraud glucose forms are frequently seen in human infections (scedosporiosis), both agar revealed fungal growth identified as S. apiospermum. as the cause of systemic disease in immunocompromised patients and eumycetoma in immunocompetent patients2. Eumycetoma is a chronic progressive granulomatous infection of the subcutaneous tissue.
    [Show full text]
  • Case Report Vertebral Osteomyelitis Caused by Scedosporium Apiospermum in an Immunocompetent Male: a Case Report
    Int J Clin Exp Med 2018;11(8):8672-8676 www.ijcem.com /ISSN:1940-5901/IJCEM0066200 Case Report Vertebral osteomyelitis caused by Scedosporium apiospermum in an immunocompetent male: a case report Dan Cao1,2*, Dajiang Li1,2*, Le Yu1,2, Hongxia Bi1,2, Rong Deng1,2, Lichun Wang1,2 1Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, P.R. China; 2Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, P.R. China. *Equal contribu- tors. Received September 25, 2017; Accepted April 25, 2018; Epub August 15, 2018; Published August 30, 2018 Abstract: We describe an extremely rare case in which Scedosporium apiospermum caused vertebral osteomy- elitis in an immunocompetent 47-year-old man after he nearly drowned in a pond. The patient was admitted to West China Hospital complaining of lower back pain. Computed tomography (CT) of the chest revealed a chest-wall abscess, and CT of the lumbar spine revealed destruction in the L-3, L-4, and L-5 vertebrae. S. apiospermum was cultured from a paravertabral necrotic secretion, and antifungal therapy with voriconazole was initiated. The lower back pain disappeared after antifungal treatment, and the previously elevated white blood cell count, pro-calcitonin level, and erythrocyte sedimentation rate returned to normal. Moreover, CT showed improvement in the condition of the chest wall and lumbar spine. We report this case to advise physicians that lower back pain in near-drowning victims should raise suspicion of vertebral osteomyelitis due to the ubiquitous fungus S. apiospermum. Keywords: Vertebral osteomyelitis, Scedosporium apiospermum, near-drowning, antifungal therapy Introduction Case description Scedosporium apiospermum, is the asexual A motorcycle was submerged in a pond owing form of the filamentous fungus Pseudallesche- to a traffic accident.
    [Show full text]
  • Scedosporium and Lomentospora Infections: Contemporary Microbiological Tools for the Diagnosis of Invasive Disease
    Journal of Fungi Review Scedosporium and Lomentospora Infections: Contemporary Microbiological Tools for the Diagnosis of Invasive Disease Sharon C.-A. Chen 1,2,*, Catriona L. Halliday 1,2, Martin Hoenigl 3,4,5 , Oliver A. Cornely 6,7,8 and Wieland Meyer 2,9,10,11 1 Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, New South Wales Health Pathology, Westmead Hospital, Westmead, Sydney, NSW 2145, Australia; [email protected] 2 Marie Bashir Institute for Infectious Diseases & Biosecurity, The University of Sydney, Sydney, NSW 2006, Australia; [email protected] 3 Division of Infectious Diseases and Global Health, University of California San Diego, San Diego, CA 92103, USA; [email protected] 4 Clinical and Translational Fungal-Working Group, University of California San Diego, San Diego, CA 92103, USA 5 Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, 8036 Graz, Austria 6 Department of Internal Medicine, Excellence Centre for Medical Mycology (ECMM), Faculty of Medicine and University Hospital Cologne, University of Cologne, 50923 Cologne, Germany; [email protected] 7 Translational Research Cologne Excellence Cluster on Cellular Responses in Aging-associated Diseases (CECAD), 50923 Cologne, Germany 8 Clinical Trials Centre Cologne (ZKS Koln), 50923 Cologne, Germany 9 Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Clinical School, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, Sydney, NSW 2006, Australia 10 Westmead Hospital (Research and Education Network), Westmead, NSW 2145, Australia 11 Westmead Institute for Medical Research, Westmead, NSW 2145, Australia * Correspondence: [email protected]; Tel.: +61-2-8890-6255 Abstract: Scedosporium/Lomentospora fungi are increasingly recognized pathogens.
    [Show full text]
  • Species-Specific Antifungal Susceptibility Patterns Of
    Species-Specific Antifungal Susceptibility Patterns of Scedosporium and Pseudallescheria Species Michaela Lackner,a,b,c G. Sybren de Hoog,d,e Paul E. Verweij,f Mohammad J. Najafzadeh,d,g Ilse Curfs-Breuker,h Corné H. Klaassen,h and Jacques F. Meisf,h Federal Institute for Drugs and Medical Devices Biosafety Laboratory, Bonn, Germanya; Institute of Microbiology, University of Innsbruck, Innsbruck, Austriab; Innsbruck c d Medical University, Division of Hygiene and Medical Microbiology, Innsbruck, Austria ; KNAW Fungal Biodiversity Centre (CBS), Utrecht, Netherlands ; Institute for Downloaded from Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, Netherlandse; Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlandsf; Department of Parasitology and Mycology, Ghaem Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Irang; and Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, Netherlandsh Since the separation of Pseudallescheria boydii and P. apiosperma in 2010, limited data on species-specific susceptibility patterns of these and other species of Pseudallescheria and its anamorph Scedosporium have been reported. This study presents the antifungal susceptibility patterns of members affiliated with both entities. Clinical and environmental isolates from a wide range of sources and origins were identified down to species level and tested according to CLSI (332 ؍ n) http://aac.asm.org/ M38-A2 against eight antifungal compounds. Whereas P. apiosperma (geometric mean MIC/minimal effective concentra- tion [MEC] values of 0.9, 2.4, 7.4, 16.2, 0.2, 0.8, 1.5, and 6.8 ␮g/ml for voriconazole, posaconazole, isavuconazole, itracona- zole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) and P.
    [Show full text]
  • The Host Immune Response to Scedosporium/Lomentospora
    Journal of Fungi Review The Host Immune Response to Scedosporium/Lomentospora Idoia Buldain, Leire Martin-Souto , Aitziber Antoran, Maialen Areitio , Leire Aparicio-Fernandez , Aitor Rementeria * , Fernando L. Hernando and Andoni Ramirez-Garcia * Fungal and Bacterial Biomics Research Group, Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Spain; [email protected] (I.B.); [email protected] (L.M.-S.); [email protected] (A.A.); [email protected] (M.A.); [email protected] (L.A.-F.); fl[email protected] (F.L.H.) * Correspondence: [email protected] (A.R.); [email protected] (A.R.-G.) Abstract: Infections caused by the opportunistic pathogens Scedosporium/Lomentospora are on the rise. This causes problems in the clinic due to the difficulty in diagnosing and treating them. This review collates information published on immune response against these fungi, since an understanding of the mechanisms involved is of great interest in developing more effective strategies against them. Sce- dosporium/Lomentospora cell wall components, including peptidorhamnomannans (PRMs), α-glucans and glucosylceramides, are important immune response activators following their recognition by TLR2, TLR4 and Dectin-1 and through receptors that are yet unknown. After recognition, cytokine synthesis and antifungal activity of different phagocytes and epithelial cells is species-specific, high- lighting the poor response by microglial cells against L. prolificans. Moreover, a great number of Scedosporium/Lomentospora antigens have been identified, most notably catalase, PRM and Hsp70 for their potential medical applicability. Against host immune response, these fungi contain evasion mechanisms, inducing host non-protective response, masking fungal molecular patterns, destructing host defense proteins and decreasing oxidative killing.
    [Show full text]
  • Treatment of Fungal Infections in Adult Pulmonary and Critical Care Patients
    American Thoracic Society Documents An Official American Thoracic Society Statement: Treatment of Fungal Infections in Adult Pulmonary and Critical Care Patients Andrew H. Limper, Kenneth S. Knox, George A. Sarosi, Neil M. Ampel, John E. Bennett, Antonino Catanzaro, Scott F. Davies, William E. Dismukes, Chadi A. Hage, Kieren A. Marr, Christopher H. Mody, John R. Perfect, and David A. Stevens, on behalf of the American Thoracic Society Fungal Working Group THIS OFFICIAL STATEMENT OF THE AMERICAN THORACIC SOCIETY (ATS) WAS APPROVED BY THE ATS BOARD OF DIRECTORS, MAY 2010 CONTENTS immune-compromised and critically ill patients, including crypto- coccosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; Introduction and rare and emerging fungal infections. Methods Antifungal Agents: General Considerations Keywords: fungal pneumonia; amphotericin; triazole antifungal; Polyenes echinocandin Triazoles Echinocandins The incidence, diagnosis, and clinical severity of pulmonary Treatment of Fungal Infections fungal infections have dramatically increased in recent years in Histoplasmosis response to a number of factors. Growing numbers of immune- Sporotrichosis compromised patients with malignancy, hematologic disease, Blastomycosis and HIV, as well as those receiving immunosupressive drug Coccidioidomycosis regimens for the management of organ transplantation or Paracoccidioidomycosis autoimmune inflammatory conditions, have significantly con- Cryptococcosis tributed to an increase in the incidence of these infections. Aspergillosis Definitive
    [Show full text]
  • Supplement Hoenigl TLID 2021 Global Guideline for the Diagnosis
    Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Hoenigl M, Salmanton-García J, Walsh TJ, et al. Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology. Lancet Infect Dis 2021; published online Feb 16. https://doi.org/10.1016/S1473-3099(20)30784-2. 1 Global guideline for the diagnosis and management of rare 2 mold infections: An initiative of the ECMM in cooperation 3 with ISHAM and ASM* 4 5 Authors 6 Martin Hoenigl (FECMM)1,2,3,54,55#, Jon Salmanton-García4,5,30,55, Thomas J. Walsh (FECMM)6, Marcio 7 Nucci (FECMM)7, Chin Fen Neoh (FECMM)8,9, Jeffrey D. Jenks2,3,10, Michaela Lackner (FECMM)11,55, Ro- 8 sanne Sprute4,5,55, Abdullah MS Al-Hatmi (FECMM)12, Matteo Bassetti13, Fabianne Carlesse 9 (FECMM)14,15, Tomas Freiberger16, Philipp Koehler (FECMM)4,5,17,30,55, Thomas Lehrnbecher18, Anil Ku- 10 mar (FECMM)19, Juergen Prattes (FECMM)1,55, Malcolm Richardson (FECMM)20,21,55,, Sanjay Revankar 11 (FECMM)22, Monica A. Slavin23,24, Jannik Stemler4,5,55, Birgit Spiess25, Saad J. Taj-Aldeen26, Adilia Warris 12 (FECMM)27, Patrick C.Y. Woo (FECMM)28, Jo-Anne H. Young29, Kerstin Albus4,30,55, Dorothee Arenz4,30,55, 13 Valentina Arsic-Arsenijevic (FECMM)31,54, Jean-Philippe Bouchara32,33, Terrence Rohan Chinniah34, Anu- 14 radha Chowdhary (FECMM)35, G Sybren de Hoog (FECMM)36, George Dimopoulos (FECMM)37, Rafael F.
    [Show full text]
  • Voriconazole Mics Are Predictive for the Outcome Of
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Repositorio Academico Digital UANL J Antimicrob Chemother 2017; 72: 1118–1122 doi:10.1093/jac/dkw532 Advance Access publication 24 December 2016 Voriconazole MICs are predictive for the outcome of Downloaded from https://academic.oup.com/jac/article-abstract/72/4/1118/2738693 by Universidad Autónoma de Nuevo León user on 14 March 2019 experimental disseminated scedosporiosis Adela Martin-Vicente1, Josep Guarro1, Gloria M. Gonzalez 2, Cornelia Lass-Flo¨rl3, Michaela Lackner3* and Javier Capilla1 1Unitat de Microbiologia, Facultat de Medicina i Cie`ncies de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Tarragona, Spain; 2Departamento de Microbiologıa, Facultad de Medicina, Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon, Mexico; 3Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria *Corresponding author. Tel: !43-512-9003-70725; E-mail: [email protected] Received 3 June 2016; returned 19 July 2016; revised 8 November 2016; accepted 13 November 2016 Background: Scedosporiosis is associated with a mortality rate of up to 90% in patients suffering from dissemi- nated infections. Recommended first-line treatment is voriconazole, but epidemiological cut-off values and clin- ical breakpoints have not been determined. Objectives: To correlate voriconazole treatment response in mice suffering from disseminated scedosporiosis with MIC values determined using CLSI broth microdilution, Etest (bioMe´rieux) and disc diffusion. Methods: Voriconazole MICs for 31 Scedosporium apiospermum strains were determined using CLSI broth micro- dilution, Etest and disc diffusion. Groups of mice were challenged intravenously with 1 out of 16 S.
    [Show full text]
  • Recurrent Scedosporium Apiospermum Mycetoma Successfully Treated by Surgical Excision and Terbinafine Treatment: a Case Report and Review of the Literature Eszter J
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Repository of the Academy's Library Tóth et al. Ann Clin Microbiol Antimicrob (2017) 16:31 DOI 10.1186/s12941-017-0195-z Annals of Clinical Microbiology and Antimicrobials CASE REPORT Open Access Recurrent Scedosporium apiospermum mycetoma successfully treated by surgical excision and terbinafine treatment: a case report and review of the literature Eszter J. Tóth1,2, Géza R. Nagy3, Mónika Homa1,2, Marianna Ábrók4, Ildikó É. Kiss4, Gábor Nagy1,2, Zsuzsanna Bata‑Csörgő3, Lajos Kemény3, Edit Urbán4, Csaba Vágvölgyi2 and Tamás Papp1,2* Abstract Background: Scedosporium apiospermum is an emerging opportunistic filamentous fungus, which is notorious for its high levels of antifungal-resistance. It is able to cause localized cutaneous or subcutaneous infections in both immu‑ nocompromised and immunocompetent persons, pulmonary infections in patients with predisposing pulmonary diseases and invasive mycoses in immunocompromised patients. Subcutaneous infections caused by this fungus frequently show chronic mycetomatous manifestation. Case report: We report the case of a 70-year-old immunocompromised man, who developed a fungal mycetoma‑ tous infection on his right leg. There was no history of trauma; the aetiological agent was identified by microscopic examination and ITS sequencing. This is the second reported case of S. apiospermum subcutaneous infections in Hungary, which was successfully treated by surgical excision and terbinafine treatment. After 7 months, the patient remained asymptomatic. Considering the antifungal susceptibility and increasing incidence of the fungus, Sce- dosporium related subcutaneous infections reported in the past quarter of century in European countries were also reviewed.
    [Show full text]