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Fernández-Ruiz M. Pharmacological management of invasive mold infections in solid organ transplant recipients. Expert Opin Pharmacother 2024; 25:239-254. [PMID: 38436619 DOI: 10.1080/14656566.2024.2326507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 02/29/2024] [Indexed: 03/05/2024]
Abstract
INTRODUCTION Solid organ transplant (SOT) recipients face an increased susceptibility to invasive fungal infection (IFI) due to filamentous fungi. Post-transplant invasive aspergillosis (IA) and mucormycosis are related to exceedingly high mortality rates and graft loss risk, and its management involve a unique range of clinical challenges. AREAS COVERED First, the current treatment recommendations for IA and mucormycosis among SOT recipients are critically reviewed, including the supporting evidence. Next, we discussed particular concerns in this patient population, such as drug-drug interactions (DDIs) between triazoles and post-transplant immunosuppression or treatment-related toxicity. The role for immunomodulatory and host-targeted therapies is also considered, as well as the theoretical impact of the intrinsic antifungal activity of calcineurin inhibitors. Finally, a personal opinion is made on future directions in the pharmacological approach to post-transplant IFI. EXPERT OPINION Despite relevant advances in the treatment of mold IFIs in the SOT setting, such as the incorporation of isavuconazole (with lower incidence of DDIs and better tolerability than voriconazole), there remains a large room for improvement in areas such as the position of combination therapy or the optimal strategy for the reduction of baseline immunosuppression. Importantly, future studies should define the specific contribution of newer antifungal agents and classes.
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Affiliation(s)
- Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
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Sartain E, Schoeppler K, Crowther B, Smith JB, Abidi MZ, Grazia TJ, Steele M, Gleason T, Porter K, Gray A. Perioperative anidulafungin combined with triazole prophylaxis for the prevention of early invasive candidiasis in lung transplant recipients. Transpl Infect Dis 2021; 23:e13692. [PMID: 34270137 DOI: 10.1111/tid.13692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 06/18/2021] [Accepted: 07/05/2021] [Indexed: 11/27/2022]
Abstract
BACKGROUND Invasive candidiasis (IC) is a substantial cause of morbidity and mortality among lung transplant recipients (LTRs). Postoperative factors include prolonged hospital stay, central lines, delayed chest closure, and dehiscence increase IC risk. Correspondingly, current guidelines propose targeted IC coverage early posttransplant with fluconazole or an echinocandin. METHODS This retrospective analysis was performed on LTRs from January 2016 to January 2020 and evaluated effectiveness of a recent protocol utilizing perioperative anidulafungin for early IC prevention in addition to long-term triazole antifungal prophylaxis. Prior to this protocol, patients were primarily established on itraconazole prophylaxis alone. The primary endpoint was proven or probable IC within 90 days after transplant. Multivariable logistic regression modeling was used to assess risk factors for invasive fungal infection (IFI). RESULTS Among 144 LTRs, there was a numerically lower incidence of IC in the protocol group, although not statistically significant (6% vs. 13%, p = 0.16). Incidence of proven or probable IFI was 7.5% in the protocol cohort and 19.5% in the pre-protocol cohort (p = 0.038). In multivariable analysis, when controlling for lung allocation score (OR 1.04, 95% CI 1.01-1.08), donor perioperative culture with fungal growth (OR 2.92, 95% CI 1.02-8.92), and dehiscence (OR 3.54, 95% CI 1.14-10.85), protocol cohort was not significantly associated with IFI (OR 0.41, 95% CI 0.12-1.23). CONCLUSIONS To our knowledge, this is the first study investigating combination triazole/echinocandin use in the early post-lung transplant period. These findings demonstrate that in-hospital anidulafungin offers unclear benefit for early IC prevention when used in combination with triazole prophylaxis.
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Affiliation(s)
- Emily Sartain
- Department of Pharmacy, University of Colorado Hospital, Aurora, Colorado, USA
| | - Kelly Schoeppler
- Department of Pharmacy, University of Colorado Hospital, Aurora, Colorado, USA
| | - Barrett Crowther
- Department of Pharmacy, University of Colorado Hospital, Aurora, Colorado, USA
| | - Joshua B Smith
- Division of Pulmonary Sciences and Critical Care, Department of Medicine, University of Colorado, Denver, Colorado, USA
| | - Maheen Z Abidi
- Division of Infectious Disease, Department of Medicine, University of Colorado, Denver, Colorado, USA
| | - Todd J Grazia
- Division of Pulmonary Diseases, Section of Advanced Lung Disease and Lung Transplantation, Baylor University Medical Center, Dallas, Texas, USA
| | - Mark Steele
- Division of Pulmonary Sciences and Critical Care, Department of Medicine, University of Colorado, Denver, Colorado, USA
| | - Terri Gleason
- Transplant Center, University of Colorado Hospital, Aurora, Colorado, USA
| | - Krista Porter
- Transplant Center, University of Colorado Hospital, Aurora, Colorado, USA
| | - Alice Gray
- Division of Pulmonary Sciences and Critical Care, Department of Medicine, University of Colorado, Denver, Colorado, USA
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Ferrarese A, Cattelan A, Cillo U, Gringeri E, Russo FP, Germani G, Gambato M, Burra P, Senzolo M. Invasive fungal infection before and after liver transplantation. World J Gastroenterol 2020; 26:7485-7496. [PMID: 33384549 PMCID: PMC7754548 DOI: 10.3748/wjg.v26.i47.7485] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 11/15/2020] [Accepted: 11/29/2020] [Indexed: 02/06/2023] Open
Abstract
Invasive infections are a major complication before liver transplantation (LT) and in the early phase after surgery. There has been an increasing prevalence of invasive fungal disease (IFD), especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure, who suffer from a profound state of immune dysfunction and receive intensive care management. In such patients, who are listed for LT, development of an IFD often worsens hepatic and extra-hepatic organ dysfunction, requiring a careful evaluation before surgery. In the post-transplant setting, the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis, even if several major issues still remain, such as duration, target population and drug type(s). Nevertheless, the development of IFD in the early phase after surgery significantly impairs graft and patient survival. This review outlines presentation, prophylactic and therapeutic strategies, and outcomes of IFD in LT candidates and recipients, providing specific considerations for clinical practice.
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Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| | - Annamaria Cattelan
- Tropical and Infectious Disease Unit, Padua University Hospital, Padua 35128, Italy
| | - Umberto Cillo
- Padua University Hospital, Hepatobiliary Surgery and Liver Transplant Center, Padua 35128, Italy
| | - Enrico Gringeri
- Padua University Hospital, Hepatobiliary Surgery and Liver Transplant Center, Padua 35128, Italy
| | | | - Giacomo Germani
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy
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Husain S, Camargo JF. Invasive Aspergillosis in solid-organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33:e13544. [PMID: 30900296 DOI: 10.1111/ctr.13544] [Citation(s) in RCA: 165] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 03/18/2019] [Indexed: 12/13/2022]
Abstract
These updated AST-IDCOP guidelines provide information on epidemiology, diagnosis, and management of Aspergillus after organ transplantation. Aspergillus is the most common invasive mold infection in solid-organ transplant (SOT) recipients, and it is the most common invasive fungal infection among lung transplant recipients. Time from transplant to diagnosis of invasive aspergillosis (IA) is variable, but most cases present within the first year post-transplant, with shortest time to onset among liver and heart transplant recipients. The overall 12-week mortality of IA in SOT exceeds 20%; prognosis is worse among those with central nervous system involvement or disseminated disease. Bronchoalveolar lavage galactomannan is preferred for the diagnosis of IA in lung and non-lung transplant recipients, in combination with other diagnostic modalities (eg, chest CT scan, culture). Voriconazole remains the drug of choice to treat IA, with isavuconazole and lipid formulations of amphotericin B regarded as alternative agents. The role of combination antifungals for primary therapy of IA remains controversial. Either universal prophylaxis or preemptive therapy is recommended in lung transplant recipients, whereas targeted prophylaxis is favored in liver and heart transplant recipients. In these guidelines, we also discuss newer antifungals and diagnostic tests, antifungal susceptibility testing, and special patient populations.
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Affiliation(s)
- Shahid Husain
- Division of Infectious Diseases, Multi-Organ Transplant Unit, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Jose F Camargo
- Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, Florida
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5
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Pre-Existing Liver Disease and Toxicity of Antifungals. J Fungi (Basel) 2018; 4:jof4040133. [PMID: 30544724 PMCID: PMC6309049 DOI: 10.3390/jof4040133] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 12/05/2018] [Accepted: 12/07/2018] [Indexed: 12/17/2022] Open
Abstract
Pre-existing liver disease in patients with invasive fungal infections further complicates their management. Altered pharmacokinetics and tolerance issues of antifungal drugs are important concerns. Adjustment of the dosage of antifungal agents in these cases can be challenging given that current evidence to guide decision-making is limited. This comprehensive review aims to evaluate the existing evidence related to antifungal treatment in individuals with liver dysfunction. This article also provides suggestions for dosage adjustment of antifungal drugs in patients with varying degrees of hepatic impairment, after accounting for established or emerging pharmacokinetic–pharmacodynamic relationships with regard to antifungal drug efficacy in vivo.
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Vekeman F, Weiss L, Aram J, Ionescu-Ittu R, Moosavi S, Xiao Y, Cheng WY, Bhak RH, Tawadrous M, Capparella MR, Montravers P, Duh MS. Retrospective cohort study comparing the risk of severe hepatotoxicity in hospitalized patients treated with echinocandins for invasive candidiasis in the presence of confounding by indication. BMC Infect Dis 2018; 18:438. [PMID: 30157797 PMCID: PMC6116432 DOI: 10.1186/s12879-018-3333-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Accepted: 08/15/2018] [Indexed: 01/01/2023] Open
Abstract
Background To compare the risk of severe hepatotoxicity with anidulafungin versus caspofungin and micafungin in hospitalized adults. Methods This retrospective cohort study combined data from two large US- based hospital electronic medical record databases. Severe hepatotoxicity was a Grade ≥ 3 liver function test (LFT) post-echinocandin initiation. Adjusted incidence rate ratios (IRRs) were estimated for anidulafungin versus caspofungin and micafungin, overall and in patients with normal baseline LFT (Grade 0). Results Treatments included anidulafungin (n = 1700), caspofungin (n = 4431), or micafungin (n = 6547). The proportions with LFT Grade ≥ 3 pre-echinocandin initiation were: anidulafungin 40.4% versus caspofungin 25.9% (p < 0.001) and micafungin 25.6% (p < 0.001). Rates of severe underlying diseases or comorbidities were: critical care admissions: 75.3% versus 52.6 and 48.6%; and organ failures: 69.4% versus 46.7 and 51.5%. Adjusted IRRs of severe hepatotoxicity for anidulafungin versus caspofungin and micafungin were 1.43 (p = 0.002) and 1.19 (p = 0.183) overall, and 0.88 (P = 0.773) and 0.97 (P = 0.945) for normal baseline LFT, respectively. Conclusions Accounting for confounders, severe hepatotoxicity risk was not significantly different across echinocandins in this real-world head-to-head study. Anidulafungin was used more frequently in patients with more comorbidities. Those with normal baseline LFT (least susceptible to confounding by indication), showed no elevated hepatotoxicity risk for anidulafungin.
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Affiliation(s)
- Francis Vekeman
- Analysis Group, Inc., 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA
| | | | | | - Raluca Ionescu-Ittu
- Analysis Group, Inc., 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA
| | | | - Yongling Xiao
- Analysis Group, Inc., 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA
| | - Wendy Y Cheng
- Analysis Group, Inc., 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA
| | - Rachel H Bhak
- Analysis Group, Inc., 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA
| | | | | | - Philippe Montravers
- Paris Diderot Sorbonne Cite University and Bichat-Claude Bernard University Hospital, Paris, France
| | - Mei Sheng Duh
- Analysis Group, Inc., 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA. .,Harvard T.H. Chan School of Public Health, Boston, MA, USA.
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7
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Ullmann AJ, Aguado JM, Arikan-Akdagli S, Denning DW, Groll AH, Lagrou K, Lass-Flörl C, Lewis RE, Munoz P, Verweij PE, Warris A, Ader F, Akova M, Arendrup MC, Barnes RA, Beigelman-Aubry C, Blot S, Bouza E, Brüggemann RJM, Buchheidt D, Cadranel J, Castagnola E, Chakrabarti A, Cuenca-Estrella M, Dimopoulos G, Fortun J, Gangneux JP, Garbino J, Heinz WJ, Herbrecht R, Heussel CP, Kibbler CC, Klimko N, Kullberg BJ, Lange C, Lehrnbecher T, Löffler J, Lortholary O, Maertens J, Marchetti O, Meis JF, Pagano L, Ribaud P, Richardson M, Roilides E, Ruhnke M, Sanguinetti M, Sheppard DC, Sinkó J, Skiada A, Vehreschild MJGT, Viscoli C, Cornely OA. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect 2018; 24 Suppl 1:e1-e38. [PMID: 29544767 DOI: 10.1016/j.cmi.2018.01.002] [Citation(s) in RCA: 926] [Impact Index Per Article: 132.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 01/02/2018] [Accepted: 01/03/2018] [Indexed: 02/06/2023]
Abstract
The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.
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Affiliation(s)
- A J Ullmann
- Department of Infectious Diseases, Haematology and Oncology, University Hospital Würzburg, Würzburg, Germany; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - J M Aguado
- Infectious Diseases Unit, University Hospital Madrid, Madrid, Spain; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - S Arikan-Akdagli
- Department of Medical Microbiology, Hacettepe University Medical School, Ankara, Turkey; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - D W Denning
- The National Aspergillosis Centre, Wythenshawe Hospital, Mycology Reference Centre Manchester, Manchester University NHS Foundation Trust, ECMM Excellence Centre of Medical Mycology, Manchester, UK; The University of Manchester, Manchester, UK; Manchester Academic Health Science Centre, Manchester, UK; European Confederation of Medical Mycology (ECMM)
| | - A H Groll
- Department of Paediatric Haematology/Oncology, Centre for Bone Marrow Transplantation, University Children's Hospital Münster, Münster, Germany; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - K Lagrou
- Department of Microbiology and Immunology, ECMM Excellence Centre of Medical Mycology, University Hospital Leuven, Leuven, Belgium; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - C Lass-Flörl
- Institute of Hygiene, Microbiology and Social Medicine, ECMM Excellence Centre of Medical Mycology, Medical University Innsbruck, Innsbruck, Austria; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - R E Lewis
- Infectious Diseases Clinic, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; ESCMID Fungal Infection Study Group (EFISG)
| | - P Munoz
- Department of Medical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias - CIBERES (CB06/06/0058), Madrid, Spain; Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - P E Verweij
- Department of Medical Microbiology, Radboud University Medical Centre, Centre of Expertise in Mycology Radboudumc/CWZ, ECMM Excellence Centre of Medical Mycology, Nijmegen, Netherlands; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - A Warris
- MRC Centre for Medical Mycology, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - F Ader
- Department of Infectious Diseases, Hospices Civils de Lyon, Lyon, France; Inserm 1111, French International Centre for Infectious Diseases Research (CIRI), Université Claude Bernard Lyon 1, Lyon, France; European Respiratory Society (ERS)
| | - M Akova
- Department of Medicine, Section of Infectious Diseases, Hacettepe University Medical School, Ankara, Turkey; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - M C Arendrup
- Department Microbiological Surveillance and Research, Statens Serum Institute, Copenhagen, Denmark; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - R A Barnes
- Department of Medical Microbiology and Infectious Diseases, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK; European Confederation of Medical Mycology (ECMM)
| | - C Beigelman-Aubry
- Department of Diagnostic and Interventional Radiology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; European Respiratory Society (ERS)
| | - S Blot
- Department of Internal Medicine, Ghent University, Ghent, Belgium; Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Australia; European Respiratory Society (ERS)
| | - E Bouza
- Department of Medical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain; CIBER Enfermedades Respiratorias - CIBERES (CB06/06/0058), Madrid, Spain; Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - R J M Brüggemann
- Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Centre of Expertise in Mycology Radboudumc/CWZ, ECMM Excellence Centre of Medical Mycology, Nijmegen, Netherlands; ESCMID Fungal Infection Study Group (EFISG)
| | - D Buchheidt
- Medical Clinic III, University Hospital Mannheim, Mannheim, Germany; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - J Cadranel
- Department of Pneumology, University Hospital of Tenon and Sorbonne, University of Paris, Paris, France; European Respiratory Society (ERS)
| | - E Castagnola
- Infectious Diseases Unit, Istituto Giannina Gaslini Children's Hospital, Genoa, Italy; ESCMID Fungal Infection Study Group (EFISG)
| | - A Chakrabarti
- Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India; European Confederation of Medical Mycology (ECMM)
| | - M Cuenca-Estrella
- Instituto de Salud Carlos III, Madrid, Spain; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - G Dimopoulos
- Department of Critical Care Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece; European Respiratory Society (ERS)
| | - J Fortun
- Infectious Diseases Service, Ramón y Cajal Hospital, Madrid, Spain; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - J-P Gangneux
- Univ Rennes, CHU Rennes, Inserm, Irset (Institut de Recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - J Garbino
- Division of Infectious Diseases, University Hospital of Geneva, Geneva, Switzerland; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - W J Heinz
- Department of Infectious Diseases, Haematology and Oncology, University Hospital Würzburg, Würzburg, Germany; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - R Herbrecht
- Department of Haematology and Oncology, University Hospital of Strasbourg, Strasbourg, France; ESCMID Fungal Infection Study Group (EFISG)
| | - C P Heussel
- Diagnostic and Interventional Radiology, Thoracic Clinic, University Hospital Heidelberg, Heidelberg, Germany; European Confederation of Medical Mycology (ECMM)
| | - C C Kibbler
- Centre for Medical Microbiology, University College London, London, UK; European Confederation of Medical Mycology (ECMM)
| | - N Klimko
- Department of Clinical Mycology, Allergy and Immunology, North Western State Medical University, St Petersburg, Russia; European Confederation of Medical Mycology (ECMM)
| | - B J Kullberg
- Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Centre of Expertise in Mycology Radboudumc/CWZ, ECMM Excellence Centre of Medical Mycology, Nijmegen, Netherlands; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - C Lange
- International Health and Infectious Diseases, University of Lübeck, Lübeck, Germany; Clinical Infectious Diseases, Research Centre Borstel, Leibniz Center for Medicine & Biosciences, Borstel, Germany; German Centre for Infection Research (DZIF), Tuberculosis Unit, Hamburg-Lübeck-Borstel-Riems Site, Lübeck, Germany; European Respiratory Society (ERS)
| | - T Lehrnbecher
- Division of Paediatric Haematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany; European Confederation of Medical Mycology (ECMM)
| | - J Löffler
- Department of Infectious Diseases, Haematology and Oncology, University Hospital Würzburg, Würzburg, Germany; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - O Lortholary
- Department of Infectious and Tropical Diseases, Children's Hospital, University of Paris, Paris, France; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - J Maertens
- Department of Haematology, ECMM Excellence Centre of Medical Mycology, University Hospital Leuven, Leuven, Belgium; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - O Marchetti
- Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Department of Medicine, Ensemble Hospitalier de la Côte, Morges, Switzerland; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - J F Meis
- Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Centre of Expertise in Mycology Radboudumc/CWZ, ECMM Excellence Centre of Medical Mycology, Nijmegen, Netherlands; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - L Pagano
- Department of Haematology, Universita Cattolica del Sacro Cuore, Roma, Italy; European Confederation of Medical Mycology (ECMM)
| | - P Ribaud
- Quality Unit, Pôle Prébloc, Saint-Louis and Lariboisière Hospital Group, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - M Richardson
- The National Aspergillosis Centre, Wythenshawe Hospital, Mycology Reference Centre Manchester, Manchester University NHS Foundation Trust, ECMM Excellence Centre of Medical Mycology, Manchester, UK; The University of Manchester, Manchester, UK; Manchester Academic Health Science Centre, Manchester, UK; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - E Roilides
- Infectious Diseases Unit, 3rd Department of Paediatrics, Faculty of Medicine, Aristotle University School of Health Sciences, Thessaloniki, Greece; Hippokration General Hospital, Thessaloniki, Greece; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - M Ruhnke
- Department of Haematology and Oncology, Paracelsus Hospital, Osnabrück, Germany; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - M Sanguinetti
- Institute of Microbiology, Fondazione Policlinico Universitario A. Gemelli - Università Cattolica del Sacro Cuore, Rome, Italy; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - D C Sheppard
- Division of Infectious Diseases, Department of Medicine, Microbiology and Immunology, McGill University, Montreal, Canada; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - J Sinkó
- Department of Haematology and Stem Cell Transplantation, Szent István and Szent László Hospital, Budapest, Hungary; ESCMID Fungal Infection Study Group (EFISG)
| | - A Skiada
- First Department of Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - M J G T Vehreschild
- Department I of Internal Medicine, ECMM Excellence Centre of Medical Mycology, University Hospital of Cologne, Cologne, Germany; Centre for Integrated Oncology, Cologne-Bonn, University of Cologne, Cologne, Germany; German Centre for Infection Research (DZIF) partner site Bonn-Cologne, Cologne, Germany; European Confederation of Medical Mycology (ECMM)
| | - C Viscoli
- Ospedale Policlinico San Martino and University of Genova (DISSAL), Genova, Italy; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM)
| | - O A Cornely
- First Department of Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece; German Centre for Infection Research (DZIF) partner site Bonn-Cologne, Cologne, Germany; CECAD Cluster of Excellence, University of Cologne, Cologne, Germany; Clinical Trials Center Cologne, University Hospital of Cologne, Cologne, Germany; ESCMID Fungal Infection Study Group (EFISG); European Confederation of Medical Mycology (ECMM); ESCMID European Study Group for Infections in Compromised Hosts (ESGICH).
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Kyriakidis I, Tragiannidis A, Munchen S, Groll AH. Clinical hepatotoxicity associated with antifungal agents. Expert Opin Drug Saf 2016; 16:149-165. [PMID: 27927037 DOI: 10.1080/14740338.2017.1270264] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Invasive fungal diseases (IFDs) are a leading cause of morbidity and mortality among immunocompromised patients with bone marrow failure syndromes, hematological malignancies, hematopoietic stem cell transplantation (HSCT), those admitted in intensive care units (ICUs) and those with prolonged febrile neutropenia. IFDs occur in a setting of multiple morbidities and are associated with case fatality rates between 30 and 70%. Along with the development of classes and compounds, the last two decades have seen substantial improvements in the prevention and management of these infections and an overall increased use of antifungal agents. Areas covered: All antifungal agents, including amphotericin B formulations, echinocandins and the triazoles, may cause hepatic toxicity that ranges from mild and asymptomatic abnormalities in liver function tests to substantial liver injury and fulminant hepatic failure. Expert opinion: The present article reviews incidence and severity of hepatotoxicity associated with different classes and agents to provide a better understanding of this specific end organ toxicity and safer use of antifungal agents A thorough understanding of the distribution, metabolism, elimination and drug-drug interactions of antifungal agents used for management of IFDs in combination with safety data from clinical trials, pharmacokinetic and pharmacodynamic studies may guide the use of antifungal treatment in patients at high risk for the development of hepatic dysfunction and in those with underlying liver damage due to cytotoxic therapy.
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Affiliation(s)
- Ioannis Kyriakidis
- a Hematology Oncology Unit, 2nd Pediatric Department , Aristotle University of Thessaloniki, University General Hospital AHEPA , Thessaloniki , Greece
| | - Athanasios Tragiannidis
- a Hematology Oncology Unit, 2nd Pediatric Department , Aristotle University of Thessaloniki, University General Hospital AHEPA , Thessaloniki , Greece
| | - Silke Munchen
- b Institute for Pharmaceutical and Medicinal Chemistry , University of Münster , Münster , Germany
| | - Andreas H Groll
- c Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology and Oncology , University Children's Hospital of Münster , Münster , Germany
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9
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Feliu J, Del Pozo JL, Azanza JR, García-Muñoz R, Zabalza A, Gorosquieta A, Pérez-Equiza E, Olavarría E. Antifungal prophylaxis with anidulafungin to minimize drug interactions with an antiepileptic treatment in a hematopoietic stem cell transplant recipient. J Clin Pharm Ther 2015; 40:601-603. [PMID: 26073924 DOI: 10.1111/jcpt.12299] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 05/18/2015] [Indexed: 01/12/2023]
Abstract
WHAT IS KNOWN AND OBJECTIVE Invasive fungal infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). This provides a clear rationale for antifungal prophylaxis in this population. A concern is the potential for drug interactions, given that most of antifungals are metabolized through the P450 cytochrome system. CASE SUMMARY We present a case of a 33-year-old woman, with a past history of high-risk epilepsy, who underwent allogeneic HSCT for a myelodysplastic syndrome. Anidulafungin was successfully used as antifungal prophylaxis to minimize drug interactions with her antiepileptic treatment. WHAT IS NEW AND CONCLUSION This is the first reported case of antifungal prophylaxis with this echinocandin in HSCT. Anidulafungin may be an option in transplant recipients with multiple risk factors for drug interactions.
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Affiliation(s)
- J Feliu
- Haematology Department, Hospital San Pedro, Logroño, Spain
| | - J L Del Pozo
- Infectious Diseases Division and Clinical Microbiology, Clinica Universidad de Navarra, Pamplona, Spain
| | - J R Azanza
- Pharmacology Department, Clinica Universidad de Navarra, Pamplona, Spain
| | - R García-Muñoz
- Haematology Department, Hospital San Pedro, Logroño, Spain
| | - A Zabalza
- Haematology Department, Complejo Hospitalario de Navarra, Pamplona, Spain
| | - A Gorosquieta
- Haematology Department, Complejo Hospitalario de Navarra, Pamplona, Spain
| | - E Pérez-Equiza
- Haematology Department, Complejo Hospitalario de Navarra, Pamplona, Spain
| | - E Olavarría
- Haematology Department, Complejo Hospitalario de Navarra, Pamplona, Spain
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10
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High-dose weekly liposomal amphotericin b antifungal prophylaxis in patients undergoing liver transplantation: a prospective phase II trial. Transplantation 2015; 99:848-54. [PMID: 25531982 DOI: 10.1097/tp.0000000000000393] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND To assess the safety and tolerability of high-dose weekly (10 mg/kg) liposomal amphotericin B (LamB) for antifungal prophylaxis in liver transplantation (LT) recipients with predefined risk factors for invasive fungal infection (IFI), a prospective phase II noncomparative trial was performed at our center over a 4-year period. METHODS In the selected LT recipients, LamB was administered weekly until hospital discharge after LT for minimum 2 weeks. Criteria for early discontinuing prophylaxis were: (i) any adverse event (AE); (ii) suspicion of IFI. Safety and tolerability were assessed according to the incidence of grades 3 to 4 AEs based on Common Toxicity Criteria (CTC) classification. Post-LT follow-up was of 180 days. RESULTS Overall, 76 patients were included. Liposomal amphotericin B was started within a median of 1 (interquartile range, 1-4) day after LT. Overall, 66 of 76 (86.8%) patients completed the prophylaxis, 10 discontinued the study protocol: 6 for infusion-related AE, 4 for suspected IFI. Adverse events consisted of five cases of lumbar pain and one case of thoracic pain which occurred after a median of 1.5 (interquartile range, 1-2) LamB infusions. None of the patients reported CTC grades 3 to 4 hypokalemia, three reported CTC grade 3 acute renal injury, none of which were deemed directly attributable to LamB. No drug-drug interactions with immunosuppressive drugs were reported, and no episode of rejection occurred during the prophylaxis. In only two of the four patients with suspected IFI was the diagnosis of invasive candidiasis confirmed. CONCLUSION Our results suggest high-dose weekly LamB may be a safe prophylactic strategy for high-risk LT recipients.
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Gad EH, Alsebaey A, Lotfy M, Eltabbakh M, Sherif AA. Complications and mortality after adult to adult living donor liver transplantation: A retrospective cohort study. Ann Med Surg (Lond) 2015. [DOI: https:/doi.org/10.1016/j.amsu.2015.04.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
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12
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Gad EH, Alsebaey A, Lotfy M, Eltabbakh M, Sherif AA. Complications and mortality after adult to adult living donor liver transplantation: A retrospective cohort study. Ann Med Surg (Lond) 2015. [DOI: https://doi.org/10.1016/j.amsu.2015.04.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
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13
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Gad EH, Alsebaey A, Lotfy M, Eltabbakh M, Sherif AA. Complications and mortality after adult to adult living donor liver transplantation: A retrospective cohort study. ANNALS OF MEDICINE AND SURGERY (2012) 2015. [PMID: 26005570 DOI: 10.1016/j.amsu.2015.04.021.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 09/30/2022]
Abstract
BACKGROUND AND AIMS Living donor liver transplantation (LDLT) is widely performed for patients to resolve the critical shortage of organs from cadavers. Despite rapid implementation of the procedure, both complications and mortality of LDLT are annoying problems. The aim of this study was to analyze complications and mortality of patients after adult to adult LDLT (A-ALDLT) in a single center. METHODS Between April 2003 and November 2013, 167 (A-ALDLT) recipients in National Liver Institute, Egypt were included. We retrospectively analyzed complications and mortality in them. RESULTS The overall incidence of complications was 86.2% (n = 144) and classified as biliary 43.7% (n = 73), vascular 21.6% (n = 36), Small for size syndrome (SFSS) 12.6% (n = 21), Gastrointestinal tract (GIT) 19.8% (n = 33), wound 12.6% (n = 21), chest 19.8% (n = 33), neurological 26.3% (n = 44), renal 21% (n = 35), intra abdominal collection 21.6% (n = 36), recurrent hepatitis C virus (HCV) 16.8% (n = 28), recurrent hepatocellular carcinoma (HCC) 2.4% (n = 4), acute rejection 19.2% (n = 32). 65 (45.1%) of 144 complicated patients died, while 10 (43.5%) of 23 non complicated died. The incidence of whole, in hospital and late mortalities were 44.9%, 28.7% and 16.2% respectively. CONCLUSIONS Mortality was higher among complicated cases where vascular complications and SFSS had significant effect on it so prevention and treatment of them is required for improving outcome.
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Affiliation(s)
- Emad Hamdy Gad
- Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Kom, Menoufiya, Egypt
| | - Ayman Alsebaey
- Hepatology Department, National Liver Institute, Menoufiya University, Shibin El-Kom, Menoufiya, Egypt
| | - Maha Lotfy
- Anesthesia Department, National Liver Institute, Menoufiya University, Shibin El-Kom, Menoufiya, Egypt
| | - Mohamed Eltabbakh
- Hepatology Department, National Liver Institute, Menoufiya University, Shibin El-Kom, Menoufiya, Egypt
| | - Ahmed Alshawadfy Sherif
- Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Kom, Menoufiya, Egypt
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Maraki S, Hamilos G, Dimopoulou D, Andrianaki AM, Karageorgiadis AS, Kyvernitakis A, Lionakis S, Kofteridis DP, Samonis G. Study on the comparative activity of echinocandins on murine gut colonization byCandida albicans. Med Mycol 2015; 53:597-602. [DOI: 10.1093/mmy/myv028] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Accepted: 03/28/2015] [Indexed: 12/18/2022] Open
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15
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Vidal E, Cervera C, Cordero E, Armiñanzas C, Carratalá J, Cisneros JM, Fariñas MC, López-Medrano F, Moreno A, Muñoz P, Origüen J, Sabé N, Valerio M, Torre-Cisneros J. Management of urinary tract infection in solid organ transplant recipients: Consensus statement of the Group for the Study of Infection in Transplant Recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI). Enferm Infecc Microbiol Clin 2015; 33:679.e1-679.e21. [PMID: 25976754 DOI: 10.1016/j.eimc.2015.03.024] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Accepted: 03/30/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND Urinary tract infections (UTIs) are one of the most common infections in solid organ transplant (SOT) recipients. METHODS Experienced SOT researchers and clinicians have developed and implemented this consensus document in support of the optimal management of these patients. A systematic review was conducted, and evidence levels based on the available literature are given for each recommendation. This article was written in accordance with international recommendations on consensus statements and the recommendations of the Appraisal of Guidelines for Research and Evaluation II (AGREE II). RESULTS Recommendations are provided on the management of asymptomatic bacteriuria, and prophylaxis and treatment of UTI in SOT recipients. The diagnostic-therapeutic management of recurrent UTI and the role of infection in kidney graft rejection or dysfunction are reviewed. Finally, recommendations on antimicrobials and immunosuppressant interactions are also included. CONCLUSIONS The latest scientific information on UTI in SOT is incorporated in this consensus document.
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Affiliation(s)
- Elisa Vidal
- Unidad Clínica de Gestión de Enfermedades Infecciosas, Instituto Maimónides de Investigación en Biomedicina de Córdoba, Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain.
| | - Carlos Cervera
- Servicio de Enfermedades Infecciosas, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain
| | - Elisa Cordero
- Unidad Clínica de Gestión de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain
| | - Carlos Armiñanzas
- Unidad de Enfermedades Infecciosas, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, IDIVAL, Santander, Spain
| | - Jordi Carratalá
- Servicio de Enfermedades Infecciosas, Hospital Universitario de Bellvitge, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Universidad de Barcelona, Barcelona, Spain
| | - José Miguel Cisneros
- Unidad Clínica de Gestión de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain
| | - M Carmen Fariñas
- Unidad de Enfermedades Infecciosas, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, IDIVAL, Santander, Spain
| | - Francisco López-Medrano
- Unidad de Enfermedades Infecciosas, Hospital Universitario 12 de Octubre, Instituto de Investigación Biomédica 12 de Octubre, Departamento de Medicina, Universidad Complutense, Madrid, Spain
| | - Asunción Moreno
- Servicio de Enfermedades Infecciosas, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain
| | - Patricia Muñoz
- Departamento de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Julia Origüen
- Unidad de Enfermedades Infecciosas, Hospital Universitario 12 de Octubre, Instituto de Investigación Biomédica 12 de Octubre, Departamento de Medicina, Universidad Complutense, Madrid, Spain
| | - Núria Sabé
- Servicio de Enfermedades Infecciosas, Hospital Universitario de Bellvitge, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Universidad de Barcelona, Barcelona, Spain
| | - Maricela Valerio
- Departamento de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Julián Torre-Cisneros
- Unidad Clínica de Gestión de Enfermedades Infecciosas, Instituto Maimónides de Investigación en Biomedicina de Córdoba, Hospital Universitario Reina Sofía, Universidad de Córdoba, Córdoba, Spain
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Gad EH, Alsebaey A, Lotfy M, Eltabbakh M, Sherif AA. Complications and mortality after adult to adult living donor liver transplantation: A retrospective cohort study. Ann Med Surg (Lond) 2015; 4:162-71. [PMID: 26005570 PMCID: PMC4434206 DOI: 10.1016/j.amsu.2015.04.021] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2015] [Revised: 03/02/2015] [Accepted: 04/20/2015] [Indexed: 02/05/2023] Open
Abstract
Background and aims Living donor liver transplantation (LDLT) is widely performed for patients to resolve the critical shortage of organs from cadavers. Despite rapid implementation of the procedure, both complications and mortality of LDLT are annoying problems. The aim of this study was to analyze complications and mortality of patients after adult to adult LDLT (A-ALDLT) in a single center. Methods: Between April 2003 and November 2013, 167 (A-ALDLT) recipients in National Liver Institute, Egypt were included. We retrospectively analyzed complications and mortality in them. Results The overall incidence of complications was 86.2% (n = 144) and classified as biliary 43.7% (n = 73), vascular 21.6% (n = 36), Small for size syndrome (SFSS) 12.6% (n = 21), Gastrointestinal tract (GIT) 19.8% (n = 33), wound 12.6% (n = 21), chest 19.8% (n = 33), neurological 26.3% (n = 44), renal 21% (n = 35), intra abdominal collection 21.6% (n = 36), recurrent hepatitis C virus (HCV) 16.8% (n = 28), recurrent hepatocellular carcinoma (HCC) 2.4% (n = 4), acute rejection 19.2% (n = 32). 65 (45.1%) of 144 complicated patients died, while 10 (43.5%) of 23 non complicated died. The incidence of whole, in hospital and late mortalities were 44.9%, 28.7% and 16.2% respectively. Conclusions: Mortality was higher among complicated cases where vascular complications and SFSS had significant effect on it so prevention and treatment of them is required for improving outcome.
Mortality was higher among complicated cases. Vascular complication was independent predictors of poor outcome. Small for size syndrome was independent predictors of poor outcome. Proper management of the previous complications improve outcome of LDLT.
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Affiliation(s)
- Emad Hamdy Gad
- Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Kom, Menoufiya, Egypt
| | - Ayman Alsebaey
- Hepatology Department, National Liver Institute, Menoufiya University, Shibin El-Kom, Menoufiya, Egypt
| | - Maha Lotfy
- Anesthesia Department, National Liver Institute, Menoufiya University, Shibin El-Kom, Menoufiya, Egypt
| | - Mohamed Eltabbakh
- Hepatology Department, National Liver Institute, Menoufiya University, Shibin El-Kom, Menoufiya, Egypt
| | - Ahmed Alshawadfy Sherif
- Hepatobiliary Surgery Department, National Liver Institute, Menoufiya University, Shibin El-Kom, Menoufiya, Egypt
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Gavaldà J, Meije Y, Fortún J, Roilides E, Saliba F, Lortholary O, Muñoz P, Grossi P, Cuenca-Estrella M. Invasive fungal infections in solid organ transplant recipients. Clin Microbiol Infect 2014; 20 Suppl 7:27-48. [DOI: 10.1111/1469-0691.12660] [Citation(s) in RCA: 134] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Zaragoza R, Ferrer R, Maseda E, Llinares P, Rodriguez A. EPICO 2.0 project. Development of educational therapeutic recommendations using the DELPHI technique on invasive candidiasis in critically ill adult patients in special situations. Rev Iberoam Micol 2014; 31:157-75. [PMID: 25113990 DOI: 10.1016/j.riam.2014.06.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2014] [Accepted: 06/02/2014] [Indexed: 10/25/2022] Open
Abstract
BACKGROUND Although there has been an improved management of invasive candidiasis in the last decade, still controversial issues remain, especially in different therapeutic critical care scenarios. AIMS We sought to identify the core clinical knowledge and to achieve high agreement recommendations required to care for critically ill adult patients with invasive candidiasis for antifungal treatment in special situations and different scenarios. METHODS Second prospective Spanish survey reaching consensus by the DELPHI technique, conducted anonymously by electronic e-mail in the first phase to 23 national multidisciplinary experts in invasive fungal infections from five national scientific societies including intensivists, anesthesiologists, microbiologists, pharmacologists and infectious disease specialists, answering 30 questions prepared by a coordination group after a strict review of literature in the last five years. The educational objectives spanned four categories, including peritoneal candidiasis, immunocompromised patients, special situations, and organ failures. The agreement among panelists in each item should be higher than 75% to be selected. In a second phase, after extracting recommendations from the selected items, a meeting was held with more than 60 specialists in a second round invited to validate the preselected recommendations. MEASUREMENTS AND MAIN RESULTS In the first phase, 15 recommendations were preselected (peritoneal candidiasis (3), immunocompromised patients (6), special situations (3), and organ failures (3)). After the second round the following 13 were validated: Peritoneal candidiasis (3): Source control and early adequate antifungal treatment is mandatory; empirical antifungal treatment is recommended in secondary nosocomial peritonitis with Candida spp. colonization risk factors and in tertiary peritonitis. Immunocompromised patients (5): consider hepatotoxicity and interactions before starting antifungal treatment with azoles in transplanted patients; treat candidemia in neutropenic adult patients with antifungal drugs at least 14 days after the first blood culture negative and until normalization of neutrophils is achieved. Caspofungin, if needed, is the echinocandin with most scientific evidence to treat candidemia in neutropenic adult patients; caspofungin is also the first choice drug to treat febrile candidemia; in neutropenic patients with candidemia remove catheter. Special situations (2): in moderate hepatocellular failure, patients with invasive candidiasis use echinocandins (preferably low doses of anidulafungin and caspofungin) and try to avoid azoles; in case of possible interactions review all the drugs involved and preferably use anidulafungin. Organ failures (3): echinocandins are the safest antifungal drugs; reconsider the use of azoles in patients under renal replacement therapy; all of the echinocandins to treat patients under continuous renal replacement therapy are accepted and do not require dosage adjustment. CONCLUSIONS Treatment of invasive candidiasis in ICU patients requires a broad range of knowledge and skills as summarized in our recommendations. These recommendations may help to optimize the therapeutic management of these patients in special situations and different scenarios and improve their outcome based on the DELPHI methodology.
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Affiliation(s)
- Rafael Zaragoza
- Servicio de Medicina Intensiva, Hospital Universitario Dr. Peset, Valencia, Spain.
| | - Ricard Ferrer
- Servicio de Medicina Intensiva, Hospital Universitario Dr. Peset, Valencia, Spain
| | - Emilio Maseda
- Servicio de Medicina Intensiva, Hospital Universitario Dr. Peset, Valencia, Spain
| | - Pedro Llinares
- Servicio de Medicina Intensiva, Hospital Universitario Dr. Peset, Valencia, Spain
| | - Alejandro Rodriguez
- Servicio de Medicina Intensiva, Hospital Universitario Dr. Peset, Valencia, Spain
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Impact of Targeted Antifungal Prophylaxis in Heart Transplant Recipients at High Risk for Early Invasive Fungal Infection. Transplantation 2014; 97:1192-7. [DOI: 10.1097/01.tp.0000441088.01723.ee] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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20
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Fagiuoli S, Colli A, Bruno R, Craxì A, Gaeta GB, Grossi P, Mondelli MU, Puoti M, Sagnelli E, Stefani S, Toniutto P, Burra P. Management of infections pre- and post-liver transplantation: report of an AISF consensus conference. J Hepatol 2014; 60:1075-89. [PMID: 24384327 DOI: 10.1016/j.jhep.2013.12.021] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 12/18/2013] [Accepted: 12/19/2013] [Indexed: 02/06/2023]
Abstract
The burden of infectious diseases both before and after liver transplantation is clearly attributable to the dysfunction of defensive mechanisms of the host, both as a result of cirrhosis, as well as the use of immunosuppressive agents. The present document represents the recommendations of an expert panel commended by the Italian Association for the Study of the Liver (AISF), on the prevention and management of infectious complications excluding hepatitis B, D, C, and HIV in the setting of liver transplantation. Due to a decreased response to vaccinations in cirrhosis as well as within the first six months after transplantation, the best timing for immunization is likely before transplant and early in the course of disease. Before transplantation, a vaccination panel including inactivated as well as live attenuated vaccines is recommended, while oral polio vaccine, Calmette-Guerin's bacillus, and Smallpox are contraindicated, whereas after transplantation, live attenuated vaccines are contraindicated. Before transplant, screening protocols should be divided into different levels according to the likelihood of infection, in order to reduce costs for the National Health Service. Recommended preoperative and postoperative prophylaxis varies according to the pathologic agent to which it is directed (bacterial vs. viral vs. fungal). Timing after transplantation greatly determines the most likely agent involved in post-transplant infections, and specific high-risk categories of patients have been identified that warrant closer surveillance. Clearly, specifically targeted treatment protocols are needed upon diagnosis of infections in both the pre- as well as the post-transplant scenarios, not without considering local microbiology and resistance patterns.
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Affiliation(s)
- Stefano Fagiuoli
- Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy.
| | | | - Raffaele Bruno
- Department of Infectious Diseases, IRCCS San Matteo, University of Pavia, Pavia, Italy
| | - Antonio Craxì
- Gastroenterology and Hepatology, Di.Bi.M.I.S., University of Palermo, Italy
| | - Giovanni Battista Gaeta
- Infectious Diseases, Department of Internal and Experimental Medicine, Second University of Naples, Italy
| | - Paolo Grossi
- Infectious & Tropical Diseases Unit, Department of Surgical & Morphological Sciences, Insubria University, Varese, Italy
| | - Mario U Mondelli
- Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo and Department of Internal Medicine, University of Pavia, Italy
| | - Massimo Puoti
- Infectious Diseases Department, Niguarda Cà Granda Hospital, Milano, Italy
| | - Evangelista Sagnelli
- Department of Mental Health and Preventive Medicine, Second University of Naples, Italy
| | - Stefania Stefani
- Department of Bio-Medical Sciences, Section of Microbiology, University of Catania, Italy
| | - Pierluigi Toniutto
- Department of Medical Sciences, Experimental and Clinical, Medical Liver Transplant Section, Internal Medicine, University of Udine, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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Current world literature. Curr Opin Organ Transplant 2013; 18:241-50. [PMID: 23486386 DOI: 10.1097/mot.0b013e32835f5709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Singh N, Singh NM, Husain S. Aspergillosis in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4:228-41. [PMID: 23465016 DOI: 10.1111/ajt.12115] [Citation(s) in RCA: 137] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- N Singh
- VA Pittsburgh Healthcare System and University of Pittsburgh, Pittsburgh, PA, USA.
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Nucci M. Use of antifungal drugs in hematology. Rev Bras Hematol Hemoter 2012; 34:383-91. [PMID: 23125547 PMCID: PMC3486829 DOI: 10.5581/1516-8484.20120095] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2012] [Accepted: 07/23/2012] [Indexed: 12/03/2022] Open
Abstract
Invasive fungal disease represents a major complication in hematological patients. Antifungal agents are frequently used in hematologic patients for different purposes. In neutropenic patients, antifungal agents may be used as prophylaxis, as empiric or preemptive therapy, or to treat an invasive fungal disease that has been diagnosed. The hematologist must be familiar with the epidemiology, diagnostic tools and strategies of antifungal use, as well as the pharmacologic proprieties of the different antifungal agents. In this paper the principal antifungal agents used in hematologic patients will be discussed as will the clinical scenarios where these agents have been used.
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Affiliation(s)
- Marcio Nucci
- Universidade Federal do Rio de Janeiro - UFRJ, Rio de Janeiro, RJ, Brazil
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