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Herrera S, Magyar U, Husain S. Invasive Aspergillosis in the Current Era. Infect Dis Clin North Am 2025:S0891-5520(25)00002-9. [PMID: 40157842 DOI: 10.1016/j.idc.2025.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/01/2025]
Abstract
Despite significant advances, aspergillosis remains a critical health concern, with an evolving epidemiology and expanding populations of at-risk patients. Historically, fewer than 10 Aspergillus species were considered clinically significant. However, advancements in diagnostic technologies, such as DNA sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, have identified previously unrecognized "cryptic" Aspergillus species. This clinical review highlights the current epidemiology, risk factors, pathogenesis, clinical presentation, diagnosis, and invasive aspergillosis (IA) treatment. Diagnosing IA necessitates a multifaceted approach, integrating clinical evaluation, imaging studies, microbiological culture, serologic tests, and advanced molecular techniques.
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Affiliation(s)
- Sabina Herrera
- Department of Infectious Diseases, Transplant Coordination Service. Hospital Clinic, University of Barcelona, Carrer de Villarroel 170, 08036, Barcelona, Spain
| | - Ursula Magyar
- Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada
| | - Shahid Husain
- Division of Infectious Diseases, UHN Antimicrobial Stewardship Program, University Health Network, University of Toronto, Toronto, Ontario, Canada.
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2
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Kimura M, Rinaldi M, Kothari S, Giannella M, Anjan S, Natori Y, Phoompoung P, Gault E, Hand J, D'Asaro M, Neofytos D, Mueller NJ, Kremer AE, Rojko T, Ribnikar M, Silveira FP, Kohl J, Cano A, Torre-Cisneros J, San-Juan R, Aguado JM, Mansoor AER, George IA, Mularoni A, Russelli G, Luong ML, AlJishi YA, AlJishi MN, Hamandi B, Selzner N, Husain S. Invasive aspergillosis in liver transplant recipients in the current era. Am J Transplant 2024; 24:2092-2107. [PMID: 38801991 DOI: 10.1016/j.ajt.2024.05.016] [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: 12/11/2023] [Revised: 04/13/2024] [Accepted: 05/22/2024] [Indexed: 05/29/2024]
Abstract
Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multicenter 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in 8 cases (13%). Twelve-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotic usage (adjusted odds ratio [aOR], 4.74; P = .03) and history of pneumonia (aOR, 48.7; P = .01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; P = .01), systemic antibiotic usage (aOR, 5.03; P = .04), and antimold prophylaxis (aOR, 11.9; P = .02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ratio [aHR], 86.9; P < .001), intensive care unit stay (aHR, 3.67; P = .02), disseminated IA (aHR, 8.98; P < .001), and dialysis (aHR, 2.93; P = .001) were identified as independent risk factors associated with 12-week all-cause mortality, while recent receipt of tacrolimus (aHR, 0.11; P = .001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted antimold prophylactic and appropriate treatment strategies against IA.
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Affiliation(s)
- Muneyoshi Kimura
- Transplant Infectious Diseases, Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Matteo Rinaldi
- Infectious Diseases Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Sagar Kothari
- Transplant Infectious Diseases, Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Maddalena Giannella
- Infectious Diseases Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Shweta Anjan
- Miami Transplant Institute, Jackson Health System, Miami, Florida, USA; Division of Infectious Diseases, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Yoichiro Natori
- Miami Transplant Institute, Jackson Health System, Miami, Florida, USA; Division of Infectious Diseases, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Pakpoom Phoompoung
- Transplant Infectious Diseases, Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada; Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Emily Gault
- Ochsner Clinical School, University of Queensland School of Medicine, Louisiana, USA
| | - Jonathan Hand
- Ochsner Health, Ochsner Clinical School, University of Queensland School of Medicine, Louisiana, USA
| | - Matilde D'Asaro
- Transplant Infectious Diseases Unit, Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland
| | - Dionysios Neofytos
- Transplant Infectious Diseases Unit, Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland
| | - Nicolas J Mueller
- Swiss Transplant Cohort Study; Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Andreas E Kremer
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
| | - Tereza Rojko
- Department of Infectious Diseases, University Medical Centre Ljubljana, Slovenia and Faculty of Medicine, University of Ljubljana, Slovenia
| | - Marija Ribnikar
- Department of Gastroenterology, University Medical Centre Ljubljana, Slovenia
| | - Fernanda P Silveira
- Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Pittsburgh, Pennsylvania, USA
| | - Joshua Kohl
- Clinical and Translational Science Institute, University of Pittsburgh, Pennsylvania, USA
| | - Angela Cano
- Centro de Investigación Biomedica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Córdoba, Spain
| | - Julian Torre-Cisneros
- Centro de Investigación Biomedica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Córdoba, Spain
| | - Rafael San-Juan
- CIBER-INFEC; Unit of Infectious Diseases, Hospital Universitario "12 de Octubre," Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Jose Maria Aguado
- CIBER-INFEC; Unit of Infectious Diseases, Hospital Universitario "12 de Octubre," Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Armaghan-E-Rehman Mansoor
- Division of Infectious Diseases, Department of Medicine, Washington University in St. Louis, Missouri, USA
| | - Ige Abraham George
- Division of Infectious Diseases, Department of Medicine, Washington University in St. Louis, Missouri, USA
| | - Alessandra Mularoni
- Department of Infectious Diseases, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (Scientific Hospitalization and Treatment Institute - Mediterranean Institute for Transplants and Highly Specialized Therapies), Palermo, Italy
| | - Giovanna Russelli
- Research Department, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (Scientific Hospitalization and Treatment Institute - Mediterranean Institute for Transplants and Highly Specialized Therapies), Palermo, Italy
| | - Me-Linh Luong
- Department of Medicine, Division of Infectious Diseases, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada
| | - Yamama A AlJishi
- Section of Infectious diseases, King Fahad Specialist Hospital Dammam, Dammam, Saudi Arabia
| | - Maram N AlJishi
- Department of Medicine, King Fahad Specialist Hospital Dammam, Dammam, Saudi Arabia
| | - Bassem Hamandi
- Department of Pharmacy, University Health Network, Toronto, Ontario, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
| | - Nazia Selzner
- Ajmera Transplant Center, University Health Network, Toronto, Ontario, Canada
| | - Shahid Husain
- Transplant Infectious Diseases, Ajmera Transplant Program, University Health Network, Toronto, Ontario, Canada.
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3
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. S2k-Leitlinie Lebertransplantation der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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4
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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Carugati M, Arif S, Yarrington ME, King LY, Harris M, Evans K, Barbas AS, Sudan DL, Perfect JR, Miller RA, Alexander BD. Limitations of antifungal prophylaxis in preventing invasive Candida surgical site infections after liver transplant surgery. Antimicrob Agents Chemother 2024; 68:e0127923. [PMID: 38299818 PMCID: PMC10916370 DOI: 10.1128/aac.01279-23] [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: 10/19/2023] [Accepted: 01/06/2024] [Indexed: 02/02/2024] Open
Abstract
Invasive primary Candida surgical site infections (IP-SSIs) are a common complication of liver transplantation, and targeted antifungal prophylaxis is an efficient strategy to limit their occurrence. We performed a retrospective single-center cohort study among adult single liver transplant recipients at Duke University Hospital in the period between 1 January 2015 and 31 December 2020. The study aimed to determine the rate of Candida IP-SSI according to the peri-transplant antifungal prophylaxis received. Of 470 adult single liver transplant recipients, 53 (11.3%) received micafungin prophylaxis, 100 (21.3%) received fluconazole prophylaxis, and 317 (67.4%) did not receive systemic antifungal prophylaxis in the peri-transplant period. Ten Candida IP-SSIs occurred among 5 of 53 (9.4%) micafungin recipients, 1 of 100 (1.0%) fluconazole recipients, and 4 of 317 (1.3%) recipients who did not receive antifungal prophylaxis. Our study highlights the limitations of antifungal prophylaxis in preventing invasive Candida IP-SSI after liver transplant surgery. We hypothesize that pathogen, host, and pharmacokinetic-related factors contributed to the occurrence of Candida IP-SSI despite antifungal prophylaxis. Our study reinforces the need for a risk-based, multi-pronged approach to fungal prevention, including targeted antifungal administration in patients with risks for invasive candidiasis and close monitoring, especially among patients with surgically complex procedures, with timely control of surgical leaks.
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Affiliation(s)
- M. Carugati
- Department of Medicine, Division of Infectious Diseases, Duke University, Durham, North Carolina, USA
| | - S. Arif
- Department of Medicine, Division of Infectious Diseases, Duke University, Durham, North Carolina, USA
| | - M. E. Yarrington
- Department of Medicine, Division of Infectious Diseases, Duke University, Durham, North Carolina, USA
| | - L. Y. King
- Department of Medicine, Division of Gastroenterology, Duke University, Durham, North Carolina, USA
| | - M. Harris
- Department of Pharmacy, Duke University, Durham, North Carolina, USA
| | - K. Evans
- Department of Pharmacy, Duke University, Durham, North Carolina, USA
| | - A. S. Barbas
- Department of Surgery, Division of Abdominal Transplant Surgery, Duke University, Durham, North Carolina, USA
| | - D. L. Sudan
- Department of Surgery, Division of Abdominal Transplant Surgery, Duke University, Durham, North Carolina, USA
| | - J. R. Perfect
- Department of Medicine, Division of Infectious Diseases, Duke University, Durham, North Carolina, USA
| | - R. A. Miller
- Department of Medicine, Division of Infectious Diseases, Duke University, Durham, North Carolina, USA
| | - B. D. Alexander
- Department of Medicine, Division of Infectious Diseases, Duke University, Durham, North Carolina, USA
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6
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Barros N, Rosenblatt RE, Phipps MM, Fomin V, Mansour MK. Invasive fungal infections in liver diseases. Hepatol Commun 2023; 7:e0216. [PMID: 37639701 PMCID: PMC10462082 DOI: 10.1097/hc9.0000000000000216] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 06/07/2023] [Indexed: 08/31/2023] Open
Abstract
Patients with liver diseases, including decompensated cirrhosis, alcohol-associated hepatitis, and liver transplant recipients are at increased risk of acquiring invasive fungal infections (IFIs). These infections carry high morbidity and mortality. Multiple factors, including host immune dysfunction, barrier failures, malnutrition, and microbiome alterations, increase the risk of developing IFI. Candida remains the most common fungal pathogen causing IFI. However, other pathogens, including Aspergillus, Cryptococcus, Pneumocystis, and endemic mycoses, are being increasingly recognized. The diagnosis of IFIs can be ascertained by the direct observation or isolation of the pathogen (culture, histopathology, and cytopathology) or by detecting antigens, antibodies, or nucleic acid. Here, we provide an update on the epidemiology, pathogenesis, diagnosis, and management of IFI in patients with liver disease and liver transplantation.
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Affiliation(s)
- Nicolas Barros
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Division of Infectious Diseases, Department of Medicine, Indiana University Health, Indianapolis, Indiana, USA
| | - Russell E. Rosenblatt
- Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA
| | - Meaghan M. Phipps
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
| | - Vladislav Fomin
- Department of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA
| | - Michael K. Mansour
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
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7
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Friedman DZP, Schwartz IS. Emerging Diagnostics and Therapeutics for Invasive Fungal Infections. Infect Dis Clin North Am 2023; 37:593-616. [PMID: 37532392 DOI: 10.1016/j.idc.2023.05.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2023]
Abstract
Recently, there have been significant advances in the diagnosis and management of invasive fungal infections. Compared with traditional fungal diagnostics, molecular assays promise improved sensitivity and specificity, the ability to test a range of samples (including noninvasive samples, ie, blood), the detection of genetic mutations associated with antifungal resistance, and the potential for a faster turnaround time. Antifungals in late-stage clinical development include agents with novel mechanisms of action (olorofim and fosmanogepix) and new members of existing classes with distinct advantages over existing antifungals in toxicity, drug-drug interactions, and dosing convenience (oteseconazole, opelconazole, rezafungin, ibrexafungerp, encochleated amphotericin B).
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Affiliation(s)
- Daniel Z P Friedman
- Section of Infectious Diseases and Global Health, The University of Chicago, 5841 South Maryland Avenue, MC5065, Chicago, IL 60637, USA
| | - Ilan S Schwartz
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, 315 Trent Drive, Durham, NC 27705, USA.
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8
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Sprute R, Nacov JA, Neofytos D, Oliverio M, Prattes J, Reinhold I, Cornely OA, Stemler J. Antifungal prophylaxis and pre-emptive therapy: When and how? Mol Aspects Med 2023; 92:101190. [PMID: 37207579 DOI: 10.1016/j.mam.2023.101190] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 04/22/2023] [Accepted: 05/05/2023] [Indexed: 05/21/2023]
Abstract
The growing pool of critically ill or immunocompromised patients leads to a constant increase of life-threatening invasive infections by fungi such as Aspergillus spp., Candida spp. and Pneumocystis jirovecii. In response to this, prophylactic and pre-emptive antifungal treatment strategies have been developed and implemented for high-risk patient populations. The benefit by risk reduction needs to be carefully weighed against potential harm caused by prolonged exposure against antifungal agents. This includes adverse effects and development of resistance as well as costs for the healthcare system. In this review, we summarise evidence and discuss advantages and downsides of antifungal prophylaxis and pre-emptive treatment in the setting of malignancies such as acute leukaemia, haematopoietic stem cell transplantation, CAR-T cell therapy, and solid organ transplant. We also address preventive strategies in patients after abdominal surgery and with viral pneumonia as well as individuals with inherited immunodeficiencies. Notable progress has been made in haematology research, where strong recommendations regarding antifungal prophylaxis and pre-emptive treatment are backed by data from randomized controlled trials, whereas other critical areas still lack high-quality evidence. In these areas, paucity of definitive data translates into centre-specific strategies that are based on interpretation of available data, local expertise, and epidemiology. The development of novel immunomodulating anticancer drugs, high-end intensive care treatment and the development of new antifungals with new modes of action, adverse effects and routes of administration will have implications on future prophylactic and pre-emptive approaches.
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Affiliation(s)
- Rosanne Sprute
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Julia A Nacov
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Dionysios Neofytos
- Division of Infectious Diseases, Transplant Infectious Disease Service, University Hospital of Geneva, Geneva, Switzerland
| | - Matteo Oliverio
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany
| | - Juergen Prattes
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; Medical University of Graz, Department of Internal Medicine, Division of Infectious Disease, Excellence Center for Medical Mycology (ECMM), Graz, Austria
| | - Ilana Reinhold
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland
| | - Oliver A Cornely
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Clinical Trials Centre Cologne (ZKS Köln), Cologne, Germany
| | - Jannik Stemler
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
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9
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Breitkopf R, Treml B, Bukumiric Z, Innerhofer N, Fodor M, Rajsic S. Invasive Fungal Infections: The Early Killer after Liver Transplantation. J Fungi (Basel) 2023; 9:655. [PMID: 37367592 DOI: 10.3390/jof9060655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 06/07/2023] [Accepted: 06/09/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND Liver transplantation is a standard of care and a life-saving procedure for end-stage liver diseases and certain malignancies. The evidence on predictors and risk factors for poor outcomes is lacking. Therefore, we aimed to identify potential risk factors for mortality and to report on overall 90-day mortality after orthotopic liver transplantation (OLT), especially focusing on the role of fungal infections. METHODS We retrospectively reviewed medical charts of all patients undergoing OLT at a tertiary university center in Europe. RESULTS From 299 patients, 214 adult patients who received a first-time OLT were included. The OLT indication was mainly due to tumors (42%, 89/214) and cirrhosis (32%, 68/214), including acute liver failure in 4.7% (10/214) of patients. In total, 8% (17/214) of patients died within the first three months, with a median time to death of 15 (1-80) days. Despite a targeted antimycotic prophylaxis using echinocandins, invasive fungal infections occurred in 12% (26/214) of the patients. In the multivariate analysis, patients with invasive fungal infections had an almost five times higher chance of death (HR 4.6, 95% CI 1.1-18.8; p = 0.032). CONCLUSIONS Short-term mortality after OLT is mainly determined by infectious and procedural complications. Fungal breakthrough infections are becoming a growing concern. Procedural, host, and fungal factors can contribute to a failure of prophylaxis. Finally, invasive fungal infections may be a potentially modifiable risk factor, but the ideal perioperative antimycotic prophylaxis has yet to be determined.
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Affiliation(s)
- Robert Breitkopf
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria
| | - Benedikt Treml
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria
| | - Zoran Bukumiric
- Institute of Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
| | - Nicole Innerhofer
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria
| | - Margot Fodor
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Sasa Rajsic
- Department of Anesthesia and Intensive Care Medicine, Medical University Innsbruck, 6020 Innsbruck, Austria
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10
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Melenotte C, Aimanianda V, Slavin M, Aguado JM, Armstrong-James D, Chen YC, Husain S, Van Delden C, Saliba F, Lefort A, Botterel F, Lortholary O. Invasive aspergillosis in liver transplant recipients. Transpl Infect Dis 2023:e14049. [PMID: 36929539 DOI: 10.1111/tid.14049] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 02/03/2023] [Accepted: 02/09/2023] [Indexed: 03/18/2023]
Abstract
BACKGROUND Liver transplantation is increasing worldwide with underlying pathologies dominated by metabolic and alcoholic diseases in developed countries. METHODS We provide a narrative review of invasive aspergillosis (IA) in liver transplant (LT) recipients. We searched PubMed and Google Scholar for references without language and time restrictions. RESULTS The incidence of IA in LT recipients is low (1.8%), while mortality is high (∼50%). It occurs mainly early (<3 months) after LT. Some risk factors have been identified before (corticosteroid, renal, and liver failure), during (massive transfusion and duration of surgical procedure), and after transplantation (intensive care unit stay, re-transplantation, re-operation). Diagnosis can be difficult and therefore requires full radiological and clinicobiological collaboration. Accurate identification of Aspergillus species is recommended due to the cryptic species, and susceptibility testing is crucial given the increasing resistance of Aspergillus fumigatus to azoles. It is recommended to reduce the dose of tacrolimus (50%) and to closely monitor the trough level when introducing voriconazole, isavuconazole, and posaconazole. Surgery should be discussed on a case-by-case basis. Antifungal prophylaxis is recommended in high-risk patients. Environmental preventative measures should be implemented to prevent outbreaks of nosocomial aspergillosis in LT recipient units. CONCLUSION IA remains a very serious disease in LT patients and should be promptly sought and, if possible, prevented by clinicians when risk factors are identified.
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Affiliation(s)
- Cléa Melenotte
- Service de Maladies Infectieuses et Tropicales, Hôpital Necker Enfants-Malades, AP-HP, Paris, France.,Faculté de Médecine, Université Paris-Cité, Paris, France
| | - Vishukumar Aimanianda
- Institut Pasteur, CNRS, National Reference Center for Invasive Mycoses and Antifungals, Molecular Mycology Unit, UMR2000, Paris, France
| | - Monica Slavin
- Department of Infectious Diseases, National Center for Infections in Cancer, Sir Peter MacCallum Cancer Centre, Melbourne, Australia.,Department of Oncology, Sir Peter MacCallum Cancer Center, University of Melbourne, Melbourne, Australia
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.,Department of Medicine, Universidad Complutense, Madrid, Spain
| | | | - Yee-Chun Chen
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Shahid Husain
- Department of Transplant Infectious Diseases, Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Christian Van Delden
- Transplant Infectious Diseases Unit, University Hospitals Geneva, Geneva, Switzerland
| | - Faouzi Saliba
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - Agnès Lefort
- Université de Paris, IAME, UMR 1137, INSERM, Paris, France.,Service de Médecine Interne, Hôpital Beaujon, AP-HP, Clichy, France
| | - Francoise Botterel
- EA Dynamyc 7380 UPEC, ENVA, Faculté de Médecine, Créteil, France.,Unité de Parasitologie-Mycologie, Département de Virologie, Bactériologie-Hygiène, Mycologie-Parasitologie, DHU VIC, CHU Henri Mondor, Créteil, France
| | - Olivier Lortholary
- Service de Maladies Infectieuses et Tropicales, Hôpital Necker Enfants-Malades, AP-HP, Paris, France.,Faculté de Médecine, Université Paris-Cité, Paris, France.,Institut Pasteur, CNRS, National Reference Center for Invasive Mycoses and Antifungals, Molecular Mycology Unit, UMR2000, Paris, France.,Paris University, Necker-Pasteur Center for Infectious Diseases and Tropical Medicine, Necker-Enfants Malades Hospital, AP-HP, IHU Imagine, Paris, France
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11
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Antunes D, Gonçalves SM, Matzaraki V, Rodrigues CS, Gonçales RA, Rocha J, Sáiz J, Marques A, Torrado E, Silvestre R, Rodrigues F, van de Veerdonk FL, Barbas C, Netea MG, Kumar V, Cunha C, Carvalho A. Glutamine Metabolism Supports the Functional Activity of Immune Cells against Aspergillus fumigatus. Microbiol Spectr 2023; 11:e0225622. [PMID: 36475892 PMCID: PMC9927096 DOI: 10.1128/spectrum.02256-22] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The reprogramming of cellular metabolism of immune cells is an essential process in the regulation of antifungal immune responses. In particular, glucose metabolism has been shown to be required for protective immunity against infection with Aspergillus fumigatus. However, given the intricate cross talk between multiple metabolic networks and signals, it is likely that cellular metabolic pathways other than glycolysis are also relevant during fungal infection. In this study, we demonstrate that glutamine metabolism is required for the activation of macrophage effector functions against A. fumigatus. Glutamine metabolism was found to be upregulated early after fungal infection and glutamine depletion or the pharmacological inhibition of enzymes involved in its metabolism impaired phagocytosis and the production of both proinflammatory and T-cell-derived cytokines. In an in vivo model, inhibition of glutaminase increased susceptibility to experimental aspergillosis, as revealed by the increased fungal burden and inflammatory pathology, and the defective cytokine production in the lungs. Moreover, genetic variants in glutamine metabolism genes were found to regulate cytokine production in response to A. fumigatus stimulation. Taken together, our results demonstrate that glutamine metabolism represents an important component of the immunometabolic response of macrophages against A. fumigatus both in vitro and in vivo. IMPORTANCE The fungal pathogen Aspergillus fumigatus can cause severe and life-threatening forms of infection in immunocompromised patients. The reprogramming of cellular metabolism is essential for innate immune cells to mount effective antifungal responses. In this study, we report the pivotal contribution of glutaminolysis to the host defense against A. fumigatus. Glutamine metabolism was essential both in vitro as well as in in vivo models of infection, and genetic variants in human glutamine metabolism genes regulated cytokine production in response to fungal stimulation. This work highlights the relevance of glutaminolysis to the pathogenesis of aspergillosis and supports a role for interindividual genetic variation influencing glutamine metabolism in susceptibility to infection.
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Affiliation(s)
- Daniela Antunes
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - Samuel M. Gonçalves
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - Vasiliki Matzaraki
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Cláudia S. Rodrigues
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - Relber A. Gonçales
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - Joana Rocha
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - Jorge Sáiz
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo CEU, CEU Universities, Madrid, Spain
| | - António Marques
- Serviço de Imuno-Hemoterapia, Hospital de Braga, Braga, Portugal
| | - Egídio Torrado
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - Ricardo Silvestre
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - Fernando Rodrigues
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - Frank L. van de Veerdonk
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Coral Barbas
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo CEU, CEU Universities, Madrid, Spain
| | - Mihai G. Netea
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
- Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany
| | - Vinod Kumar
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Cristina Cunha
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Guimarães/Braga, Portugal
| | - Agostinho Carvalho
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, Guimarães/Braga, Portugal
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12
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Incidence of Invasive Fungal Infections in Liver Transplant Recipients under Targeted Echinocandin Prophylaxis. J Clin Med 2023; 12:jcm12041520. [PMID: 36836055 PMCID: PMC9960065 DOI: 10.3390/jcm12041520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/11/2023] [Accepted: 02/13/2023] [Indexed: 02/17/2023] Open
Abstract
Invasive fungal infections (IFIs) are one of the most important infectious complications after liver transplantation, determining morbidity and mortality. Antimycotic prophylaxis may impede IFI, but a consensus on indication, agent, or duration is still missing. Therefore, this study aimed to investigate the incidence of IFIs under targeted echinocandin antimycotic prophylaxis in adult high-risk liver transplant recipients. We retrospectively reviewed all patients undergoing a deceased donor liver transplantation at the Medical University of Innsbruck in the period from 2017 to 2020. Of 299 patients, 224 met the inclusion criteria. We defined patients as being at high risk for IFI if they had two or more prespecified risk factors and these patients received prophylaxis. In total, 85% (190/224) of the patients were correctly classified according to the developed algorithm, being able to predict an IFI with a sensitivity of 89%. Although 83% (90/109) so defined high-risk recipients received echinocandin prophylaxis, 21% (23/109) still developed an IFI. The multivariate analysis identified the age of the recipient (hazard ratio-HR = 0.97, p = 0.027), split liver transplantation (HR = 5.18, p = 0.014), massive intraoperative blood transfusion (HR = 24.08, p = 0.004), donor-derived infection (HR = 9.70, p < 0.001), and relaparotomy (HR = 4.62, p = 0.003) as variables with increased hazard ratios for an IFI within 90 days. The fungal colonization at baseline, high-urgency transplantation, posttransplant dialysis, bile leak, and early transplantation showed significance only in a univariate model. Notably, 57% (12/21) of the invasive Candida infections were caused by a non-albicans species, entailing a markedly reduced one-year survival. The attributable 90-day mortality rate of an IFI after a liver transplant was 53% (9/17). None of the patients with invasive aspergillosis survived. Despite targeted echinocandin prophylaxis, there is still a notable risk for IFI. Consequently, the prophylactic use of echinocandins must be critically questioned regarding the high rate of breakthrough infections, the increased occurrence of fluconazole-resistant pathogens, and the higher mortality rate in non-albicans Candida species. Adherence to the internal prophylaxis algorithms is of immense importance, bearing in mind the high IFI rates in case algorithms are not followed.
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13
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Liu Y, Lan C, Qin S, Qin Z, Zhang Z, Zhang P, Cao W. Efficacy of anti-fungal agents for invasive fungal infection prophylaxis in liver transplant recipients: A network meta-analysis. Mycoses 2022; 65:906-917. [PMID: 35899464 DOI: 10.1111/myc.13508] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 07/14/2022] [Accepted: 07/23/2022] [Indexed: 11/30/2022]
Abstract
At present, there is still a lack of effective invasive fungal prophylaxis therapy in liver transplant recipients (LTRs). This study aimed to analysis the latest evidence on efficacy of current prophylactic anti-fungal therapy, and systematically compare between anti-fungal agents and placebo by a fixed-effects meta-analysis in all randomised controlled trials. A network meta-analysis was performed for invasive fungal infection (IFI) among different agents in 14 randomised controlled trials, in which 10 anti-fungal approaches were identified. Overall, anti-fungal prophylaxis reduced the rate of IFI (RR 0.30, 95% CI 0.18-0.52) and proven IFI (RR 0.27, 95% CI 0.14-0.53) when compared to placebo. In the network meta-analysis, an equivalent reduction in the rate of IFI was observed in fluconazole (OR 4.70, 95% CI 1.22-18.10), itraconazole (OR 5.82, 95% CI 1.10-30.71) and Liposomal amphotericin B (LAmB, OR 5.74, 95% CI 1.29-25.58) groups when compared with placebo. Anidulafungin might be the most effective agents in IFI prevention; however, this superiority did not meet statistically significance. Our study indicated that fluconazole, echinocandins and LAmB are equivalent in efficacy. Of which, fluconazole is recommended for the prevention of IFI in LTRs due to its efficacy, economics and compliance.
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Affiliation(s)
- Yusi Liu
- Department of Pharmacy, Shenzhen Luohu People's Hospital, Shenzhen, China
| | - Chunhai Lan
- Department of Orthopedic Surgery, Shenzhen Luohu People's Hospital, Shenzhen, China
| | - Sibei Qin
- Department of Pharmacy, Shenzhen Luohu People's Hospital, Shenzhen, China
| | - Zhuo Qin
- Department of Pharmacy, Shenzhen Luohu People's Hospital, Shenzhen, China
| | - Zhiqiang Zhang
- Department of Pharmacy, Shenzhen Luohu People's Hospital, Shenzhen, China
| | - Peng Zhang
- Department of Pharmacy, Shenzhen Luohu People's Hospital, Shenzhen, China
| | - Weiling Cao
- Department of Pharmacy, Shenzhen Luohu People's Hospital, Shenzhen, China
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14
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Campos-Varela I, Blumberg EA, Giorgio P, Kotton CN, Saliba F, Wey EQ, Spiro M, Raptis DA, Villamil F. What is the optimal antimicrobial prophylaxis to prevent postoperative infectious complications after liver transplantation? A systematic review of the literature and expert panel recommendations. Clin Transplant 2022; 36:e14631. [PMID: 35257411 DOI: 10.1111/ctr.14631] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 02/28/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Antimicrobial prophylaxis is well-accepted in the liver transplant (LT) setting. Nevertheless, optimal regimens to prevent bacterial, viral, and fungal infections are not defined. OBJECTIVES To identify the optimal antimicrobial prophylaxis to prevent post-LT bacterial, fungal, and cytomegalovirus (CMV) infections, to improve short-term outcomes, and to provide international expert panel recommendations. DATA SOURCES Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. PROSPERO ID CRD42021244976. RESULTS Of 1853 studies screened, 34 were included for this review. Bacterial, CMV, and fungal antimicrobial prophylaxis were evaluated separately. Pneumocystis jiroveccii pneumonia (PJP) antimicrobial prophylaxis was analyzed separately from other fungal infections. Overall, eight randomized controlled trials, 21 comparative studies, and five observational noncomparative studies were included. CONCLUSIONS Antimicrobial prophylaxis is recommended to prevent bacterial, CMV, and fungal infection to improve outcomes after LT. Universal antibiotic prophylaxis is recommended to prevent postoperative bacterial infections. The choice of antibiotics should be individualized and length of therapy should not exceed 24 hours (Quality of Evidence; Low | Grade of Recommendation; Strong). Both universal prophylaxis and preemptive therapy are strongly recommended for CMV prevention following LT. The choice of one or the other strategy will depend on individual program resources and experiences, as well as donor and recipient serostatus. (Quality of Evidence; Low | Grade of Recommendation; Strong). Antifungal prophylaxis is strongly recommended for LT recipients at high risk of developing invasive fungal infections. The drug of choice remains controversial. (Quality of Evidence; High | Grade of Recommendation; Strong). PJP prophylaxis is strongly recommended. Length of prophylaxis remains controversial. (Quality of Evidence; Very Low | Grade of Recommendation; Strong).
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Affiliation(s)
- Isabel Campos-Varela
- Liver Unit, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Emily A Blumberg
- Perelman School of Medicine at the University of Pennsylvania, Philadephia, Pennsylvania, USA
| | - Patricia Giorgio
- Department of Infectious Disease, Hospital Británico, Buenos Aires City, Argentina
| | - Camille N Kotton
- Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, Boston, USA
| | - Fauzi Saliba
- APHP, Hopital Paul Brousse, Université Paris Saclay, INSERM unit No. 1193, Villejuif, France
| | - Emmanuel Q Wey
- ILDH, Division of Medicine, University College London Medical School, London, UK.,Centre for Clinical Microbiology, Division of Infection & Immunity, UCL, London, UK.,Department of Infection, Royal Free London NHS Foundation Trust, London, UK
| | - Michael Spiro
- Department of Anesthesia and Intensive Care Medicine, Royal Free Hospital, London, UK.,Division of Surgery & Interventional Science, University College London, London, UK
| | - Dimitri Aristotle Raptis
- Division of Surgery & Interventional Science, University College London, London, UK.,Clinical Service of HPB Surgery and Liver Transplantation, Royal Free Hospital, London, UK
| | - Federico Villamil
- Liver Transplantation Unit, British Hospital, Buenos Aires City, Argentina.,Hepatology and Liver Transplantation Unit, Hospital El Cruce, Florencio Varela, Buenos Aires Province, Argentina
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15
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Radcliffe C, Patel KK, Azar MM, Koff A, Belfield KD, Peaper DR, Topal JE, Malinis M. Rectal screening for azole Non‐susceptible
Candida
species in patients undergoing liver transplantation. Transpl Infect Dis 2022; 24:e13811. [DOI: 10.1111/tid.13811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/04/2022] [Accepted: 02/08/2022] [Indexed: 11/28/2022]
Affiliation(s)
| | - Kishan K. Patel
- Yale School of Medicine Section of Infectious Diseases New Haven CT USA
| | - Marwan M. Azar
- Yale School of Medicine Section of Infectious Diseases New Haven CT USA
| | - Alan Koff
- UC Davis School of Medicine Section of Infectious Diseases Sacramento CA USA
| | | | - David R. Peaper
- Yale School of Medicine Department of Laboratory Medicine New Haven CT USA
| | - Jeffrey E. Topal
- Yale School of Medicine Section of Infectious Diseases New Haven CT USA
| | - Maricar Malinis
- Yale School of Medicine Section of Infectious Diseases New Haven CT USA
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16
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Khalid M, Neupane R, Anjum H, Surani S. Fungal infections following liver transplantation. World J Hepatol 2021; 13:1653-1662. [PMID: 34904035 PMCID: PMC8637669 DOI: 10.4254/wjh.v13.i11.1653] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 06/24/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023] Open
Abstract
With increasing morbidity and mortality from chronic liver disease and acute liver failure, the need for liver transplantation is on the rise. Most of these patients are extremely vulnerable to infections as they are immune-compromised and have other chronic co-morbid conditions. Despite the recent advances in practice and improvement in diagnostic surveillance and treatment modalities, a major portion of these patients continue to be affected by post-transplant infections. Of these, fungal infections are particularly notorious given their vague and insidious onset and are very challenging to diagnose. This mini-review aims to discuss the incidence of fungal infections following liver transplantation, the different fungi involved, the risk factors, which predispose these patients to such infections, associated diagnostic challenges, and the role of prophylaxis. The population at risk is increasingly old and frail, suffering from various other co-morbid conditions, and needs special attention. To improve care and to decrease the burden of such infections, we need to identify the at-risk population with more robust clinical and diagnostic parameters. A more robust global consensus and stringent guidelines are needed to fight against resistant microbes and maintain the longevity of current antimicrobial therapies.
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Affiliation(s)
- Madiha Khalid
- Department of Medicine, Orlando Health Medical Center, Orlando, FL 32806, United States
| | - Ritesh Neupane
- Department of Medicine, Penn State Health Milton S Hershey Medical Center, Hershey, PA 17033, United States
| | - Humayun Anjum
- Department of Medicine, University of North Texas, Denton, TX 76203, United States
| | - Salim Surani
- Department of Pulmonary Critical Care and Sleep Medicine, Texas A&M Health Science Center, Corpus Christi, TX 78405, United States.
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17
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Invasive Candidiasis in Liver Transplant Recipients: A Review. CURRENT FUNGAL INFECTION REPORTS 2021. [DOI: 10.1007/s12281-021-00426-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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18
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Odysseos G, Mayr U, Bozsaki G, Seidensticker C, Ehmer U, Schmid RM, Lahmer T, Dill V. Isavuconazole and Liposomal Amphotericin B as Successful Combination Therapy of Refractory Invasive Candidiasis in a Liver Transplant Recipient: A Case Report and Literature Review. Mycopathologia 2021; 187:113-120. [PMID: 34718931 PMCID: PMC8807427 DOI: 10.1007/s11046-021-00599-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 10/15/2021] [Indexed: 11/30/2022]
Abstract
Invasive fungal infections in liver transplant recipients are associated with elevated morbidity and mortality and pose a challenge to the treating physicians. Despite of lacking clinical data, the use of antifungal combination therapy is often considered to improve response rates in an immunocompromised patient population. We herein report a case of refractory invasive candidiasis in a liver transplant recipient treated successfully with a combination of isavuconazole und high-dose liposomal amphotericin B. The antimycotic combination treatment was able to clear a bloodstream infection with C. glabrata and led to regression of bilomas among tolerable side effects. The use of the above-mentioned antifungal combination therapy in a liver transplant recipient has not been reported previously. This case highlights the efficacy and safety of antifungal combination therapy in immunocompromised patients with refractory invasive candidiasis.
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Affiliation(s)
- Georgios Odysseos
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Ulrich Mayr
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Gabor Bozsaki
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Christian Seidensticker
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Ursula Ehmer
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Roland M Schmid
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Tobias Lahmer
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany
| | - Veronika Dill
- Klinik und Poliklinik für Innere Medizin III, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Straße 22, 81675, Munich, Germany.
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19
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Gatti M, Rinaldi M, Ferraro G, Toschi A, Caroccia N, Arbizzani F, Raschi E, Poluzzi E, Pea F, Viale P, Giannella M. Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta-analysis. Mycoses 2021; 64:1317-1327. [PMID: 34387004 PMCID: PMC9292189 DOI: 10.1111/myc.13362] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/03/2021] [Accepted: 08/10/2021] [Indexed: 12/24/2022]
Abstract
INTRODUCTION Although echinocandins are recommended as first-line prophylaxis for high-risk orthotopic liver transplant (OLT) recipients, occurrence of breakthrough-invasive fungal infections (IFIs) remains a serious concern. We aim to assess the risk of breakthrough IFIs among OLT recipients exposed to prophylaxis with echinocandins compared to other antifungals. MATERIALS AND METHODS Two authors independently searched PubMed-MEDLINE, Embase, study registries and reference lists from inception to March 2021, to retrieve randomised controlled trials (RCTs) or observational studies comparing efficacy and safety of echinocandins vs other antifungals for prophylaxis in OLT recipients. Data were independently extracted from two authors, and the quality of included studies was independently assessed according to ROB 2.0 tool for RCTs and ROBINS-I tool for observational studies. The primary outcome was occurrence of breakthrough IFI at the end of prophylaxis (EOP). RESULTS 698 articles were screened, and ten studies (3 RCTs and 7 observational) were included. No difference between echinocandins and other antifungals in terms of breakthrough IFIs at the EOP emerged both from RCTs (odds ratio [OR] 0.85, 95% CI 0.24-2.99) and observational studies (OR 1.43, 95% CI 0.28-7.40). No difference emerged also for secondary outcomes. In the subgroup comparison between echinocandins and polyenes, a trend for higher risk of breakthrough IFI at the EOP (OR 4.82, 95% CI 0.97-24.03) was noted. CONCLUSIONS Echinocandins do not seem to be associated with increased risk of breakthrough IFIs in OLT recipients. However, the large diversity in the comparator group hinders a definitive interpretation. Further studies exploring the relationship between echinocandin use and breakthrough IFIs according to specific comparators are warranted.
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Affiliation(s)
- Milo Gatti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.,SSD Clinical Pharmacology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Rinaldi
- Infectious Disease Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giuseppe Ferraro
- Infectious Disease Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Alice Toschi
- Infectious Disease Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Natascia Caroccia
- Infectious Disease Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Federica Arbizzani
- Infectious Disease Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Emanuel Raschi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Elisabetta Poluzzi
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Federico Pea
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.,SSD Clinical Pharmacology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Pierluigi Viale
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.,Infectious Disease Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maddalena Giannella
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.,Infectious Disease Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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20
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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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21
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Fungal Infections in Liver Transplant Recipients. J Fungi (Basel) 2021; 7:jof7070524. [PMID: 34210106 PMCID: PMC8304186 DOI: 10.3390/jof7070524] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/25/2021] [Accepted: 06/21/2021] [Indexed: 01/03/2023] Open
Abstract
Invasive fungal infections (IFIs) are one of the most feared complications associated with liver transplantation, with high rates of morbidity and mortality. We discuss the most common invasive fungal infections in the setting of liver transplant, including Candida, Aspergillus, and Cryptococcal infections, and some less frequent but devastating mold infections. Further, we evaluate the use of prophylaxis to prevent invasive fungal infection in this population as a promising mechanism to reduce risks to patients after liver transplant.
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22
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Gioia F, Filigheddu E, Corbella L, Fernández-Ruiz M, López-Medrano F, Pérez-Ayala A, Aguado JM, Fariñas MC, Arnaiz F, Calvo J, Cifrian JM, Gonzalez-Rico C, Vidal E, Torre-Cisneros J, Ras MM, Pérez S, Sabe N, López-Soria LM, Rodríguez-Alvarez RJ, Montejo JM, Valerio M, Machado M, Muñoz P, Linares L, Bodro M, Moreno A, Fernández-Cruz A, Cantón R, Moreno S, Martin-Davila P, Fortún J. Invasive aspergillosis in solid organ transplantation: Diagnostic challenges and differences in outcome in a Spanish national cohort (Diaspersot study). Mycoses 2021; 64:1334-1345. [PMID: 33934405 DOI: 10.1111/myc.13298] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 04/18/2021] [Accepted: 04/26/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND The diagnosis of invasive aspergillosis (IA) can be problematic in solid organ transplantation (SOT). The prognosis greatly varies according to the type of transplant, and the impact of prophylaxis is not well defined. PATIENTS AND METHODS The Diaspersot cohort analyses the impact of IA in SOT in Spain during the last 10 years. Proven and probable/putative IA was included. RESULTS We analysed 126 cases of IA. The incidences of IA were as follows: 6.5%, 2.9%, 1.8% and 0.6% for lung, heart, liver and kidney transplantation, respectively. EORTC/MSG criteria confirmed only 49.7% of episodes. Tree-in-bud sign or ground-glass infiltrates were present in 56.3% of patients, while serum galactomannan (optical density index >0.5) was positive in 50.6%. A total of 41.3% received combined antifungal therapy. Overall mortality at 3 months was significantly lower (p < 0.001) in lung transplant recipients (14.8%) than in all other transplants [globally: 48.6%; kidney 52.0%, liver 58.3%, heart 31.2%, and combined 42.9%]. Fifty-four percent of episodes occurred despite the receipt of antifungal prophylaxis, and in 10%, IA occurred during prophylaxis (breakthrough infection), with both nebulised amphotericin (in lung transplant recipients) and candins (in the rest). CONCLUSIONS Invasive aspergillosis diagnostic criteria, applied to SOT patients, may differ from those established for haematological patients. IA in lung transplants has a higher incidence, but is associated with a better prognosis than other transplants. Combination therapy is frequently used for IA in SOT. Prophylactic measures require optimisation of its use within this population.
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Affiliation(s)
- Francesca Gioia
- Infectious Diseases Department, Hospital Ramón y Cajal, IRYCIS (Instituto Ramón y Cajal de Investigación Sanitaria), Universidad de Alcalá, Madrid, Spain
| | - Eta Filigheddu
- Infectious Diseases Department, Hospital Ramón y Cajal, IRYCIS (Instituto Ramón y Cajal de Investigación Sanitaria), Universidad de Alcalá, Madrid, Spain
| | - Laura Corbella
- Infectious Diseases Unit, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain.,Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain
| | - Mario Fernández-Ruiz
- Infectious Diseases Unit, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain.,Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain
| | - Francisco López-Medrano
- Infectious Diseases Unit, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain.,Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain
| | - Ana Pérez-Ayala
- Microbiology Department, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain
| | - Jose María Aguado
- Infectious Diseases Unit, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain.,Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain
| | - Maria Carmen Fariñas
- Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.,Infectious Diseases Unit, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Cantabria, Spain
| | - Francisco Arnaiz
- Infectious Diseases Unit, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Cantabria, Spain
| | - Jorge Calvo
- Microbiology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Spain
| | - Jose Maria Cifrian
- Pneumology Department, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Spain
| | - Claudia Gonzalez-Rico
- Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.,Infectious Diseases Unit, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Cantabria, Spain
| | - Elisa Vidal
- Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.,Infectious Diseases Unit, Maimonides Institute for Biomedical Research (IMIBIC), Hospital Universitario Reina Sofía-IMIBIC-Universidad de Cordoba, Cordoba, Spain
| | - Julian Torre-Cisneros
- Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.,Infectious Diseases Unit, Maimonides Institute for Biomedical Research (IMIBIC), Hospital Universitario Reina Sofía-IMIBIC-Universidad de Cordoba, Cordoba, Spain
| | - Maria Mar Ras
- Infectious Disease Department, Hospital Universitari Bellvitge, University of Barcelona, Barcelona, Spain
| | - Sandra Pérez
- Infectious Disease Department, Hospital Universitari Bellvitge, University of Barcelona, Barcelona, Spain
| | - Nuria Sabe
- Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.,Infectious Disease Department, Hospital Universitari Bellvitge, University of Barcelona, Barcelona, Spain
| | | | | | - José Miguel Montejo
- Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.,Infectious Disease Unit, Hospital Universitario Cruces, Barakaldo, Spain
| | - Maricela Valerio
- Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Marina Machado
- Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Patricia Muñoz
- Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Laura Linares
- Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.,Infectious Diseases Department, Hospital Clinic of Barcelona, IDIBAPS, University of Barcelona, Spain
| | - Marta Bodro
- Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.,Infectious Diseases Department, Hospital Clinic of Barcelona, IDIBAPS, University of Barcelona, Spain
| | - Asuncion Moreno
- Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.,Infectious Diseases Department, Hospital Clinic of Barcelona, IDIBAPS, University of Barcelona, Spain
| | - Ana Fernández-Cruz
- Infectious Diseases Unit, Internal Medicine Department, Hospital Universitario Puerta de Hierro-Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Madrid, Spain
| | - Rafael Cantón
- Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.,Microbiology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Santiago Moreno
- Infectious Diseases Department, Hospital Ramón y Cajal, IRYCIS (Instituto Ramón y Cajal de Investigación Sanitaria), Universidad de Alcalá, Madrid, Spain
| | - Pilar Martin-Davila
- Infectious Diseases Department, Hospital Ramón y Cajal, IRYCIS (Instituto Ramón y Cajal de Investigación Sanitaria), Universidad de Alcalá, Madrid, Spain.,Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain
| | - Jesús Fortún
- Infectious Diseases Department, Hospital Ramón y Cajal, IRYCIS (Instituto Ramón y Cajal de Investigación Sanitaria), Universidad de Alcalá, Madrid, Spain.,Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain
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23
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Rinaldi M, Bartoletti M, Ferrarese A, Franceschini E, Campoli C, Coladonato S, Pascale R, Tedeschi S, Gatti M, Cricca M, Ambretti S, Siniscalchi A, Morelli MC, Cescon M, Cillo U, Di Benedetto F, Burra P, Mussini C, Cristini F, Lewis R, Viale P, Giannella M. Breakthrough invasive fungal infection after liver transplantation in patients on targeted antifungal prophylaxis: A prospective multicentre study. Transpl Infect Dis 2021; 23:e13608. [PMID: 33768656 PMCID: PMC8519035 DOI: 10.1111/tid.13608] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 03/08/2021] [Accepted: 03/14/2021] [Indexed: 01/21/2023]
Abstract
Objective To investigate the rate of and the risk factors for breakthrough‐IFI (b‐IFI) after orthotopic liver transplantation (OLT) according to the new definition proposed by Mycoses‐Study‐Group‐Education‐and‐Research‐Consortium (MSG‐ERC) and the European‐Confederation‐of‐Medical‐Mycology (ECMM). Methods Multicenter prospective study of adult patients who underwent OLT at three Italian hospitals, from January 2015 to December 2018. Targeted antifungal prophylaxis (TAP) protocol was developed and shared among participating centers. Follow‐up was 1‐year after OLT. B‐IFI was defined as infection occurring during exposure to antifungal prophylaxis. Risk factors for b‐IFI were analyzed among patients exposed to prophylaxis by univariable analysis. Results We enrolled 485 OLT patients. Overall compliance to TAP protocol was 64.3%, 220 patients received antifungal prophylaxis, 172 according to TAP protocol. Twenty‐nine patients were diagnosed of IFI within 1 year after OLT. Of them, 11 presented with b‐IFI within 17 (IQR 11‐33) and 16 (IQR 4‐30) days from OLT and from antifungal onset, respectively. Then out of 11 patients with b‐IFI were classified as having high risk of IFI and were receiving anti‐mould prophylaxis, nine with echinocandins and one with polyenes. Comparison of patients with and without b‐IFI showed significant differences for prior Candida colonization, need of renal replacement therapy after OLT, re‐operation, and CMV infection (whole blood CMV‐DNA >100 000 copies/mL). Although non‐significant, a higher rate of b‐IFI in patients on echinocandins was observed (8.2% vs 1.8%, P = .06). Conclusions We observed 5% of b‐IFI among OLT patients exposed to antifungal prophylaxis. The impact of echinocandins on b‐IFI risk in this setting should be further explored.
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Affiliation(s)
- Matteo Rinaldi
- Division of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Michele Bartoletti
- Division of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Alberto Ferrarese
- Multivisceral Transplant Unit (Gastroenterology), Department of Surgery Oncology and Gastroenterology, Surgical and Gastroenterological Sciences, Padua University Hospital, Padua, Italy
| | - Erica Franceschini
- Infectious Diseases Unit, Department of Nephrology Dialysis and Transplant Unit, University Hospital of Modena, Modena, Italy
| | - Caterina Campoli
- Division of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Simona Coladonato
- Division of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Renato Pascale
- Division of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Sara Tedeschi
- Division of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Milo Gatti
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Monica Cricca
- Operative Unit of Clinical Microbiology, PoliclinicoSant' Orsola Malpighi, University of Bologna, Bologna, Italy
| | - Simone Ambretti
- Infectious Diseases Unit, Department of Nephrology Dialysis and Transplant Unit, University Hospital of Modena, Modena, Italy
| | - Antonio Siniscalchi
- Division of Anesthesia, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maria Cristina Morelli
- Division of Internal Medicine for the Treatment of Severe Organ Failure, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Cescon
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.,Division of Liver and Multiorgan Transplant, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Umberto Cillo
- Department of Surgical, Oncological, and Gastroenterological Sciences, Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padova, Italy
| | - Fabrizio Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit (Gastroenterology), Department of Surgery Oncology and Gastroenterology, Surgical and Gastroenterological Sciences, Padua University Hospital, Padua, Italy
| | - Cristina Mussini
- Infectious Diseases Unit, Department of Nephrology Dialysis and Transplant Unit, University Hospital of Modena, Modena, Italy
| | - Francesco Cristini
- Infectious Diseases Unit, AUSL Romagna Infermi Hospital Rimini, Rimini, Italy
| | - Russell Lewis
- Division of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Pierluigi Viale
- Division of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Maddalena Giannella
- Division of Infectious Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
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24
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Neofytos D, Garcia-Vidal C, Lamoth F, Lichtenstern C, Perrella A, Vehreschild JJ. Invasive aspergillosis in solid organ transplant patients: diagnosis, prophylaxis, treatment, and assessment of response. BMC Infect Dis 2021; 21:296. [PMID: 33761875 PMCID: PMC7989085 DOI: 10.1186/s12879-021-05958-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 03/04/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Invasive aspergillosis (IA) is a rare complication in solid organ transplant (SOT) recipients. Although IA has significant implications on graft and patient survival, data on diagnosis and management of this infection in SOT recipients are still limited. METHODS Discussion of current practices and limitations in the diagnosis, prophylaxis, and treatment of IA and proposal of means of assessing treatment response in SOT recipients. RESULTS Liver, lung, heart or kidney transplant recipients have common as well as different risk factors to the development of IA, thus each category needs a separate evaluation. Diagnosis of IA in SOT recipients requires a high degree of awareness, because established diagnostic tools may not provide the same sensitivity and specificity observed in the neutropenic population. IA treatment relies primarily on mold-active triazoles, but potential interactions with immunosuppressants and other concomitant therapies need special attention. CONCLUSIONS Criteria to assess response have not been sufficiently evaluated in the SOT population and CT lesion dynamics, and serologic markers may be influenced by the underlying disease and type and severity of immunosuppression. There is a need for well-orchestrated efforts to study IA diagnosis and management in SOT recipients and to develop comprehensive guidelines for this population.
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Affiliation(s)
- Dionysios Neofytos
- Service des Maladies Infectieuses, Hôpitaux Universitaires de Genève, Rue Gabrielle-Perret-Gentil 4, Geneva, Switzerland.
| | - Carolina Garcia-Vidal
- Servicio de Enfermedades Infecciosas, Hospital Clínic de Barcelona-IDIBAPS, Universitat de Barcelona, FungiCLINIC Research group (AGAUR), Barcelona, Spain
| | - Frédéric Lamoth
- Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, 1011, Lausanne, Switzerland
- Department of Laboratories, Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland
| | - Christoph Lichtenstern
- Department of Anaesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, Heidelberg, Germany
| | - Alessandro Perrella
- VII Department of Infectious Disease and Immunology, Hospital D. Cotugno, Naples, Italy
- CLSE-Liver Transplant Unit, Hospital A. Cardarelli, Naples, Italy
| | - Jörg Janne Vehreschild
- Medical Department II, Hematology and Oncology, University Hospital of Frankfurt, Frankfurt, Germany
- Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany
- German Centre for Infection Research, partner site Bonn-Cologne, University of Cologne, Cologne, Germany
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25
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Chea N, Sapiano MRP, Zhou L, Epstein L, Guh A, Edwards JR, Allen-Bridson K, Russo V, Watkins J, Pouch SM, Magill SS. Rates and causative pathogens of surgical site infections attributed to liver transplant procedures and other hepatic, biliary, or pancreatic procedures, 2015-2018. Transpl Infect Dis 2021; 23:e13589. [PMID: 33617680 PMCID: PMC8380253 DOI: 10.1111/tid.13589] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 02/08/2021] [Indexed: 01/22/2023]
Abstract
Liver transplant recipients are at high risk for surgical site infections (SSIs). Limited data are available on SSI epidemiology following liver transplant procedures (LTPs). We analyzed data on SSIs from 2015 to 2018 reported to CDC's National Healthcare Safety Network to determine rates, pathogen distribution, and antimicrobial resistance after LTPs and other hepatic, biliary, or pancreatic procedures (BILIs). LTP and BILI SSI rates were 5.7% and 5.9%, respectively. The odds of SSI after LTP were lower than after BILI (adjusted odds ratio = 0.70, 95% confidence interval 0.57-0.85). Among LTP SSIs, 43.1% were caused by Enterococcus spp., 17.2% by Candida spp., and 15.0% by coagulase-negative Staphylococcus spp. (CNS). Percentages of SSIs caused by Enterococcus faecium or CNS were higher after LTPs than BILIs, whereas percentages of SSIs caused by Enterobacteriaceae, Enterococcus faecalis, or viridans streptococci were higher after BILIs. Antimicrobial resistance was common in LTP SSI pathogens, including E. faecium (69.4% vancomycin resistant); Escherichia coli (68.8% fluoroquinolone non-susceptible and 44.7% extended spectrum cephalosporin [ESC] non-susceptible); and Klebsiella pneumoniae and K. oxytoca (39.4% fluoroquinolone non-susceptible and 54.5% ESC non-susceptible). National LTP SSI pathogen and resistance data can help prioritize studies to determine effective interventions to prevent SSIs and reduce antimicrobial resistance in liver transplant recipients.
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Affiliation(s)
- Nora Chea
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Mathew R P Sapiano
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.,Lantana Consulting Group, Inc, East Thetford, VT, USA
| | - Liang Zhou
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.,CACI Inc., Atlanta, GA, USA
| | - Lauren Epstein
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Alice Guh
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Jonathan R Edwards
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Katherine Allen-Bridson
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Victoria Russo
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.,CACI Inc., Atlanta, GA, USA
| | - Jennifer Watkins
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.,CACI Inc., Atlanta, GA, USA
| | | | - Shelley S Magill
- Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
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26
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Miesel L, Cushion MT, Ashbaugh A, Lopez SR, Ong V. Efficacy of Rezafungin in Prophylactic Mouse Models of Invasive Candidiasis, Aspergillosis, and Pneumocystis Pneumonia. Antimicrob Agents Chemother 2021; 65:e01992-20. [PMID: 33318018 PMCID: PMC8092522 DOI: 10.1128/aac.01992-20] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 12/07/2020] [Indexed: 12/19/2022] Open
Abstract
Antifungal prophylaxis is recommended to prevent invasive fungal disease caused by Candida spp., Aspergillus spp., and Pneumocystis jirovecii in patients at risk for opportunistic infections, such as allogeneic blood or marrow transplant recipients, patients with hematological disease undergoing chemotherapy, or patients on immunosuppressive therapies. Current approaches to antifungal prophylaxis require multiple agents to cover these key fungi. Rezafungin, a novel echinocandin designed for next-generation properties (e.g., greater stability and long-acting pharmacokinetics for once-weekly dosing), has demonstrated in vitro activity against Candida and Aspergillus spp. and efficacy against Pneumocystis spp. biofilms. Rezafungin was evaluated in in vivo studies of prophylactic efficacy using immunosuppressed mouse models of invasive candidiasis, aspergillosis, and Pneumocystis pneumonia. Rezafungin reduction of Candida CFU burden was generally greater with increasing drug concentrations (5, 10, or 20 mg/kg) and when rezafungin was administered closer to the time of fungal challenge (day -1, -3, or -5). Similarly, in the aspergillosis model, survival rates increased with drug concentrations and when rezafungin was administered closer to the time of fungal challenge. Against Pneumocystismurina, rezafungin significantly reduced trophic nuclei and asci counts at all doses tested. Rezafungin prevented infection at the two higher doses compared to vehicle and had comparable activity to the active control trimethoprim-sulfamethoxazole at human equivalent doses for prevention. These findings support phase 3 development of rezafungin and the potential for single-agent prophylaxis against invasive fungal disease caused by Candida spp., Aspergillus spp., and Pneumocystis jirovecii.
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Affiliation(s)
- Lynn Miesel
- Pharmacology Discovery Services, Taipei, Taiwan
| | - Melanie T Cushion
- University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
- Cincinnati VAMC, Cincinnati, Ohio, USA
| | - Alan Ashbaugh
- University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
- Cincinnati VAMC, Cincinnati, Ohio, USA
| | | | - Voon Ong
- Cidara Therapeutics, Inc., San Diego, California, USA
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27
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Chakravarti A, Butler-Laporte G, Carrier FM, Bilodeau M, Huard G, Corsilli D, Savard P, Luong ML. Targeted caspofungin prophylaxis for invasive aspergillosis in high-risk liver transplant recipients, a single-center experience. Transpl Infect Dis 2021; 23:e13568. [PMID: 33450126 DOI: 10.1111/tid.13568] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 11/04/2020] [Accepted: 01/03/2021] [Indexed: 01/18/2023]
Abstract
BACKGROUND Invasive aspergillosis (IA) is a rare but highly lethal complication after orthotopic liver transplantation (OLT). Targeted antifungal prophylaxis has been proposed as a strategy to prevent IA among orthotopic liver transplant recipient (OLTr), but limited data are available to support its efficacy. METHOD We conducted a single-center, retrospective, before and after cohort study, comparing IA incidences among OLTr who did not receive antifungal prophylaxis after transplantation (cohort 1) to OLTr who received targeted antifungal prophylaxis after liver transplantation (cohort 2). Patients in cohort 2 received caspofungin prophylaxis if they presented one of the following risk factors: retransplantation, acute liver failure, dialysis, or Aspergillus colonization prior to transplantation. The primary outcome was IA at 90 days after transplantation. RESULTS A total of 391 OLTr were included in the study; 181 patients in the cohort 1 (no prophylaxis) and 210 patients in the cohort 2 (targeted prophylaxis). Among patients in cohort 2, 19% (40/ 210) were considered at high risk for IA and 85% (34/40) of those received caspofungin prophylaxis. The incidence of IA at 90 days was 3.3% (6/ 181) and 0.5% (1/ 210), in cohort 1 and 2, respectively (OR 0.14; 95%CI 0.01-0.83; P = .03). Ninety-day mortality was similar among the two cohorts (3.9% (7/181) and 2.4% (5/210) in cohort 1 and 2, respectively (OR 0.61; 95% 0.18-1.93; P = .40)). The 90-day mortality among the OLTs with IA was 71% (5/7). CONCLUSION Targeted caspofungin prophylaxis was associated with lower rate of IA.
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Affiliation(s)
- Arpita Chakravarti
- Division of Infectious Disease, Department of Medicine, University of Montreal Hospital Center, Montreal, QC, Canada
| | - Guillaume Butler-Laporte
- Division of Infectious Disease, Department of Medicine, McGill University Health Center, Montreal, QC, Canada
| | - Francois Martin Carrier
- Department of Anesthesiology, University of Montreal Hospital Center, Montreal, QC, Canada.,Division of Critical Care, Department of Medicine, University of Montreal Hospital Center, Montreal, QC, Canada
| | - Marc Bilodeau
- Division of Hepatology, Department of Medicine, University of Montreal Hospital Center, Montreal, QC, Canada
| | - Genevieve Huard
- Division of Hepatology, Department of Medicine, University of Montreal Hospital Center, Montreal, QC, Canada
| | - Daniel Corsilli
- Division of Critical Care, Department of Medicine, University of Montreal Hospital Center, Montreal, QC, Canada.,Division of Hepatology, Department of Medicine, University of Montreal Hospital Center, Montreal, QC, Canada
| | - Patrice Savard
- Division of Infectious Disease, Department of Medicine, University of Montreal Hospital Center, Montreal, QC, Canada
| | - Me-Linh Luong
- Division of Infectious Disease, Department of Medicine, University of Montreal Hospital Center, Montreal, QC, Canada
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28
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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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29
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Lum L, Lee A, Vu M, Strasser S, Davis R. Epidemiology and risk factors for invasive fungal disease in liver transplant recipients in a tertiary transplant center. Transpl Infect Dis 2020; 22:e13361. [PMID: 32510755 DOI: 10.1111/tid.13361] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 03/29/2020] [Accepted: 05/27/2020] [Indexed: 01/07/2023]
Abstract
BACKGROUND Invasive fungal disease (IFD) in liver transplant recipients causes significant morbidity and mortality. We aim to describe institutional epidemiology and risk factors for IFD in the liver transplant population. METHODS We conducted a retrospective cohort study of all adult liver transplant recipients in our institution from 2005 to October 2015 to describe the epidemiology of patients with proven and probable IFD according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. To determine risk factors for IFD, a case-control study was also conducted. Cases were defined as liver transplant recipients with proven or probable IFD, and controls were defined as liver transplant recipients without IFD. Each case was matched to two controls by age (±10 years of age), gender, and time of transplant (within one year of the case). RESULTS 28/554 (5.1%) patients developed IFD. Candidiasis (n = 11; 39.3%), Aspergillosis (n = 10; 35.7%), and Cryptococcosis (n = 3; 10.7%) were the most common fungal infections in the proven and probable IFD groups. Mold infections occurred in 13 (46.4%) cases. Reoperation, roux-en-y anastomosis, and massive intraoperative transfusion of ≥40 units of cellular blood products were major risk factors for IFD in the multivariate analysis. CONCLUSION Candida and Aspergillus are the most common causes of IFD in liver transplantation in our center. There is significant overlap in risk factors for such infections post-transplantation. In our cohort, critically ill patients with complicated perioperative course seem to predispose them to mold infections post-transplantation, but larger studies are required to better delineate risk factors for mold infection as well as determine the efficacy and optimal duration of mold prophylaxis in liver transplantation. With increasing echinocandin use for antifungal prophylaxis, it is also important to monitor for emerging antifungal resistance.
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Affiliation(s)
- Lionel Lum
- Department of Infectious Diseases and Microbiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Andie Lee
- Department of Infectious Diseases and Microbiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.,Faculty of Medicine, University of Sydney, Sydney, NSW, Australia
| | - Monica Vu
- University of New South Wales, Sydney, NSW, Australia
| | - Simone Strasser
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Rebecca Davis
- Department of Infectious Diseases and Microbiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
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30
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Risk prediction for candidemia in surgical intensive care unit patients. North Clin Istanb 2020; 7:348-353. [PMID: 33043259 PMCID: PMC7521091 DOI: 10.14744/nci.2020.27136] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 03/25/2020] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE Patients in surgical intensive care units are thought to be at the highest risk for developing candidemia, especially patients undergoing abdominal surgery. The present study aims to investigate risk factors for candidemia in patients with abdominal surgery. METHODS A retrospective study was undertaken that involved patients admitted to the surgical ICU between January 2016 and January 2017. All postoperative adult patients (>18 years old) who underwent abdominal surgery were included in this study. RESULTS During the one-year study period, 49 patients developed candidemia. Thirty-five of candida isolates were non-albicans strains. Of them, 25 (51%) isolates were Candida parapsilosis, eight (16.3%) isolates were C. glabrata, one (2%) isolate was C. tropicalis and one (2%) isolate was C. kefyr. The median age of all patients enrolled in this study was 60.5±15.6 years. In univariate analysis, the duration of the hospital stays, intensive care unit stay, type of surgery, respiratory failure, total parenteral nutrition, transfusion and use of central venous catheter were significantly higher in patients with candidemia. In multivariate analysis, duration of hospital and intensive care unit stay and use of central venous catheter was associated with an increased risk of candidemia. The mortality rate of case patients was 36.7%. CONCLUSION Patients undergoing abdominal surgery are at increased risk of candidemia, especially the patients with prolonged intensive care unit/hospital stay and the patients with a central venous catheters. Antifungal prophylaxis may be considered for patients with increased risk.
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31
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A Multicenter, Randomized, Open-Label Study to Compare Micafungin with Fluconazole in the Prophylaxis of Invasive Fungal Infections in Living-Donor Liver Transplant Recipients. J Gastrointest Surg 2020; 24:832-840. [PMID: 31066013 DOI: 10.1007/s11605-019-04241-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 04/21/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Although invasive fungal infections (IFIs) contribute to substantial morbidity and mortality in liver transplant recipients, only a few randomized studies analyzed the results of antifungal prophylaxis with echinocandins. The aim of this open-label, non-inferiority study was to evaluate the efficacy and safety of micafungin in the prophylaxis of IFIs in living-donor liver transplantation recipients (LDLTRs), with fluconazole as the comparator. METHODS LDLTRs (N = 172) from five centers were randomized 1:1 to receive intravenous micafungin 100 mg/day or fluconazole 100~200 mg/day (intravenous or oral). A non-inferiority of micafungin was tested against fluconazole. RESULTS The per-protocol set included 144 patients without major clinical trial protocol violations: 69 from the micafungin group and 75 from the fluconazole group. Mean age of the study patients was 54.2 years and mean model for end-stage liver disease (MELD) score amounted to 16.5. Clinical success rates in the micafungin and fluconazole groups were 95.65% and 96.10%, respectively (difference: - 0.45%; 90% confidence interval [CI]: - 6.93%, 5.59%), which demonstrated micafungin's non-inferiority (the lower bound for the 90% CI exceeded - 10%). The study groups did not differ significantly in terms of the secondary efficacy endpoints: absence of IFIs at the end of the prophylaxis and the end of the study, time to proven IFI, fungal-free survival, and adverse reactions. A total of 17 drug-related adverse events were observed in both groups; none of them was serious and all resolved. CONCLUSION Micafungin can be used as an alternative to fluconazole in the prevention of IFIs in LDLTRs. CLINICAL TRIALS REGISTRATION NCT01974375.
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32
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Prophylaxis and Treatment of Invasive Aspergillosis: Who and How of Prophylaxis, Treatment, and New Therapies. CURRENT TREATMENT OPTIONS IN INFECTIOUS DISEASES 2020. [DOI: 10.1007/s40506-020-00213-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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33
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Märtson AG, Bakker M, Blokzijl H, Verschuuren EAM, Berger SP, Span LFR, van der Werf TS, Alffenaar JWC. Exploring failure of antimicrobial prophylaxis and pre-emptive therapy for transplant recipients: a systematic review. BMJ Open 2020; 10:e034940. [PMID: 31915177 PMCID: PMC6955515 DOI: 10.1136/bmjopen-2019-034940] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 11/29/2019] [Accepted: 12/05/2019] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVES Infections remain a threat for solid organ and stem cell transplant recipients. Antimicrobial prophylaxis and pre-emptive therapy have improved survival of these patients; however, the failure rates of prophylaxis are not negligible. The aim of this systematic review is to explore the reasons behind failure of antimicrobial prophylaxis and pre-emptive therapy. SETTING This systematic review included prospective randomised controlled trials and prospective single-arm studies. PARTICIPANTS The studies included were on prophylaxis and pre-emptive therapy of opportunistic infections in transplant recipients. Studies were included from databases MEDLINE, CENTRAL and Embase published until October first 2018. PRIMARY AND SECONDARY OUTCOME MEASURES Primary outcome measures were breakthrough infections, adverse events leading to stopping of treatment, switching medication or dose reduction. Secondary outcome measures were acquired resistance to antimicrobials, antifungals or antivirals and death. RESULTS From 3317 identified records, 30 records from 24 studies with 2851 patients were included in the systematic review. Seventeen focused on prophylactic and pre-emptive treatment of cytomegalovirus and seven studies on invasive fungal infection. The main reasons for failure of prophylaxis and pre-emptive therapy were adverse events and breakthrough infections, which were described in 54% (13 studies) and 38% (9 studies) of the included studies, respectively. In 25%, six of the studies, a detailed description of patients who experienced failure of prophylaxis or pre-emptive therapy was unclear or lacking. CONCLUSIONS Our results show that although failure is reported in the studies, the level of detail prohibits a detailed analysis of failure of prophylaxis and pre-emptive therapy. Clearly reporting on patients with a negative outcome should be improved. We have provided guidance on how to detect failure early in a clinical setting in accordance to the results from this systematic review. PROSPERO REGISTRATION NUMBER CRD42017077606.
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Affiliation(s)
- Anne-Grete Märtson
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Martijn Bakker
- Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Hans Blokzijl
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Erik A M Verschuuren
- Department of Pulmonary Diseases and Tuberculosis, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Stefan P Berger
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Lambert F R Span
- Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Tjip S van der Werf
- Department of Pulmonary Diseases and Tuberculosis, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Jan-Willem C Alffenaar
- Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- The University of Sydney, Sydney Pharmacy School, Sydney, New South Wales, Australia
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34
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Uno T, Wada K, Hosomi K, Matsuda S, Ikura MM, Takenaka H, Terakawa N, Oita A, Yokoyama S, Kawase A, Takada M. Drug interactions between tacrolimus and clotrimazole troche: a data mining approach followed by a pharmacokinetic study. Eur J Clin Pharmacol 2019; 76:117-125. [PMID: 31654150 DOI: 10.1007/s00228-019-02770-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 09/24/2019] [Indexed: 12/16/2022]
Abstract
PURPOSE This study investigated the effects of clotrimazole troche on the risk of transplant rejection and the pharmacokinetics of tacrolimus. METHODS The data mining approach was used to investigate whether the use of clotrimazole increased the risk of transplant rejection in patients receiving tacrolimus therapy. Patient data were acquired from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2017. Next, we retrospectively investigated the effect of clotrimazole troche on tacrolimus pharmacokinetics in seven patients who underwent heart transplantation between March and December 2017. RESULTS The FAERS subset data indicated a significant association between transplant rejection and tacrolimus with clotrimazole [reporting odds ratio 1.92, 95% two-sided confidence interval (95% CI) 1.43-2.58, information component 0.81, 95% CI 0.40-1.23]. The pharmacokinetic study demonstrated a significant correlation between trough concentration (C0) and area under the concentration-time curve of tacrolimus after discontinuation of clotrimazole (R2 = 0.60, P < 0.05) but not before its discontinuation. Furthermore, the median clearance/bioavailability of tacrolimus after discontinuation of clotrimazole was 2.2-fold greater than that before its discontinuation (0.27 vs. 0.59 L/h/kg, P < 0.05). The median C0 decreased from 10.7 ng/mL on the day after discontinuation of clotrimazole to 6.5 ng/mL at 1 day and 5.3 ng/mL at 2 days after its discontinuation. CONCLUSION Immediate dose adjustments of tacrolimus may be beneficial to avoid transplant rejection when clotrimazole troche is added or discontinued.
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Affiliation(s)
- Takaya Uno
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-osaka, Japan
- Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, Higashi-osaka, Japan
| | - Kyoichi Wada
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan
| | - Kouichi Hosomi
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-osaka, Japan
- Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, Higashi-osaka, Japan
| | - Sachi Matsuda
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Megumi Morii Ikura
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Hiromi Takenaka
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Nobue Terakawa
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Akira Oita
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Satoshi Yokoyama
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-osaka, Japan
- Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, Higashi-osaka, Japan
| | - Atsushi Kawase
- Department of Pharmacy, Faculty of Pharmacy, Kindai University, Higashi-osaka, Japan
| | - Mitsutaka Takada
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-osaka, Japan.
- Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, Higashi-osaka, Japan.
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35
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Welte T, Len O, Muñoz P, Romani L, Lewis R, Perrella A. Invasive mould infections in solid organ transplant patients: modifiers and indicators of disease and treatment response. Infection 2019; 47:919-927. [PMID: 31576498 DOI: 10.1007/s15010-019-01360-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2019] [Accepted: 09/18/2019] [Indexed: 02/06/2023]
Abstract
PURPOSE Invasive mould infections, in particular invasive aspergillosis (IA), are comparatively frequent complications of immunosuppression in patients undergoing solid organ transplantation (SOT). Guidelines provide recommendations as to the procedures to be carried out to diagnose and treat IA, but only limited advice for SOT recipients. METHODS Literature review and expert consensus summarising the existing evidence related to prophylaxis, diagnosis, treatment and assessment of response to IA and infections by Mucorales in SOT patients RESULTS: Response to therapy should be assessed early and at regular intervals. No indications of improvement should lead to a prompt change of the antifungal treatment, to account for possible infections by Mucorales or other moulds such as Scedosporium. Imaging techniques, especially CT scan and possibly angiography carried out at regular intervals during early and long-term follow-up and coupled with a careful clinical diagnostic workout, should be evaluated as diagnostic tools and outcome predictors, and standardised to improve therapy monitoring. The role of biomarkers such as the galactomannan test and PCR, as well as selected inflammation parameters, has not yet been definitively assessed in the SOT population and needs to be studied further. The therapeutic workup should consider a reduction of immunosuppressive therapy. CONCLUSIONS The role of immunosuppression and immune tolerance mechanisms in the response to invasive fungal infection treatment is an important factor in the SOT population and should not be underestimated. The choice of the antifungal should consider not only their toxicity but also their effects on the immune system, two features that are intertwined.
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Affiliation(s)
- Tobias Welte
- Department of Respiratory Medicine, Hannover Medical School, Carl Neuberg Str 1, 30625, Hannover, Germany.
| | - Oscar Len
- Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - Patricia Muñoz
- Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid, Spain
- Medicine Department, Universidad Complutense de Madrid, CIBER Enfermedades Respiratorias-CIBERES (CB06/06/0058), Madrid, Spain
| | - Luigina Romani
- Department of Experimental Medicine, School of Medicine, University of Perugia, 06132, Perugia, Italy
| | - Russell Lewis
- Infectious Diseases Hospital, S. Orsola-Malpighi, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Alessandro Perrella
- VII, Department of Infectious Disease and Immunology, Hospital D. Cotugno, Naples, Italy
- CLSE-Liver Transplant Unit, Hospital A. Cardarelli, Naples, Italy
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36
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Cornely OA, Hoenigl M, Lass-Flörl C, Chen SCA, Kontoyiannis DP, Morrissey CO, Thompson GR. Defining breakthrough invasive fungal infection-Position paper of the mycoses study group education and research consortium and the European Confederation of Medical Mycology. Mycoses 2019; 62:716-729. [PMID: 31254420 PMCID: PMC6692208 DOI: 10.1111/myc.12960] [Citation(s) in RCA: 92] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 06/26/2019] [Accepted: 06/27/2019] [Indexed: 12/14/2022]
Abstract
Breakthrough invasive fungal infections (IFIs) have emerged as a significant problem in patients receiving systemic antifungals; however, consensus criteria for defining breakthrough IFI are missing. This position paper establishes broadly applicable definitions of breakthrough IFI for clinical research. Representatives of the Mycoses Study Group Education and Research Consortium (MSG-ERC) and the European Confederation of Medical Mycology (ECMM) reviewed the relevant English literature for definitions applied and published through 2018. A draft proposal for definitions was developed and circulated to all members of the two organisations for comment and suggestions. The authors addressed comments received and circulated the updated document for approval. Breakthrough IFI was defined as any IFI occurring during exposure to an antifungal drug, including fungi outside the spectrum of activity of an antifungal. The time of breakthrough IFI was defined as the first attributable clinical sign or symptom, mycological finding or radiological feature. The period defining breakthrough IFI depends on pharmacokinetic properties and extends at least until one dosing interval after drug discontinuation. Persistent IFI describes IFI that is unchanged/stable since treatment initiation with ongoing need for antifungal therapy. It is distinct from refractory IFI, defined as progression of disease and therefore similar to non-response to treatment. Relapsed IFI occurs after treatment and is caused by the same pathogen at the same site, although dissemination can occur. These proposed definitions are intended to support the design of future clinical trials and epidemiological research in clinical mycology, with the ultimate goal of increasing the comparability of clinical trial results.
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Affiliation(s)
- Oliver A Cornely
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
- Department I of Internal Medicine, ECMM Center of Excellence for Medical Mycology, German Centre for Infection Research, Partner Site Bonn-Cologne (DZIF), University of Cologne, Cologne, Germany
- Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Cologne, Germany
| | - Martin Hoenigl
- Division of Infectious Diseases, University of California San Diego, San Diego, CA, USA
- Division of Pulmonology and Section of Infectious Diseases, Medical University of Graz, Graz, Austria
| | - Cornelia Lass-Flörl
- Division of Hygiene and Microbiology, ECMM Excellence Center for Medical Mycology, Medical University Innsbruck, Innsbruck, Austria
| | - Sharon C-A Chen
- Centre for Infectious Diseases and Microbiology, Laboratory Services, ICPMR, New South Wales Health Pathology, Westmead Hospital, Centre for Infectious Diseases and Microbiology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Dimitrios P Kontoyiannis
- Department of Infectious Diseases, Infection Control, and Employee Health, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
| | - C Orla Morrissey
- Infectious Diseases, Alfred Health and Monash University, Melbourne, VIC, Australia
| | - George R Thompson
- Departments of Medical Microbiology and Immunology and Internal Medicine Division of Infectious Diseases, UC-Davis Medical Center, Sacramento, CA, USA
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Jorgenson MR, Descourouez JL, Marka NA, Leverson GE, Smith JA, Andes DR, Fernandez LA, Foley DP. A targeted fungal prophylaxis protocol with static dosed fluconazole significantly reduces invasive fungal infection after liver transplantation. Transpl Infect Dis 2019; 21:e13156. [PMID: 31390109 DOI: 10.1111/tid.13156] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 07/10/2019] [Accepted: 08/01/2019] [Indexed: 12/22/2022]
Abstract
BACKGROUND Invasive fungal infection (IFI) after liver transplant (LTx) is associated with extensive morbidity and mortality. Targeted prophylaxis reduces risk, but qualifying criteria, drug of choice and regimen are unclear and compliance is inconsistent. OBJECTIVE Assess the impact of a risk factor-based fungal prophylaxis protocol (FPP) after LTx on fungal infection rates, fungal epidemiology, and transplant outcomes. METHODS Observational cohort study of adult LTx recipients between July 1, 2009, and June 30, 2017. Patients in the FPP group were given a set dose of 400 mg fluconazole without renal adjustment on POD 1-14 via pharmacist delegation protocol. RESULTS One hundred and eighty-nine patients met inclusion criteria; 50 in the FPP and 139 in the pre-implementation comparator group. Of those who would be considered high-risk, 22.3% received antifungal prophylaxis prior to FPP implementation vs 92% after implementation (P < .0001). There were significantly fewer fungal infections in the FPP group at 1 year (12.5% vs 26.6%, P = .03). IFI in the pre-implementation control group was due to Candida species in 95% of cases; 30% were species with reduced fluconazole susceptibility. IFI in the FPP group was due to Candida species in all cases, and no isolates had reduced fluconazole susceptibility. Aspergillus did not account for any IFI between the groups. One-year patient and graft survival were similar between groups. In a multivariable model accounting for patient and donor age, donor type, MELD, and cold ischemic time, FPP was protective against fungal infection (HR 0.3, P = .015). FPP did not significantly impact graft survival (HR 0.4, P = .14), but trended toward improved patient survival. (HR 0.18, P = .06). CONCLUSION Implementation of a targeted FPP utilizing static dosing of fluconazole 400 mg × 14 days to those that meet high-risk criteria significantly reduces invasive fungal infection after liver transplant. Use of this protocol did not adversely affect fungal epidemiology and may have a positive impact on allograft and patient survival. Future large prospective studies are needed to better evaluate survival impact.
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Affiliation(s)
- Margaret R Jorgenson
- Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Jillian L Descourouez
- Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Nicholas A Marka
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA
| | - Glen E Leverson
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA
| | - Jeannina A Smith
- Division of Infectious Disease, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA
| | - David R Andes
- Division of Infectious Disease, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA
| | - Luis A Fernandez
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA
| | - David P Foley
- Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA
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Uno T, Wada K, Matsuda S, Ikura M, Takenaka H, Terakawa N, Oita A, Yokoyama S, Kawase A, Hosomi K, Takada M. Clotrimazole troches can alter everolimus pharmacokinetics in post-transplant patients: A case report. Br J Clin Pharmacol 2019; 85:2176-2178. [PMID: 31243774 DOI: 10.1111/bcp.14017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 05/10/2019] [Accepted: 05/17/2019] [Indexed: 11/30/2022] Open
Affiliation(s)
- Takaya Uno
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan.,Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-osaka, Japan.,Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, Higashi-osaka, Japan
| | - Kyoichi Wada
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan
| | - Sachi Matsuda
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Megumi Ikura
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Hiromi Takenaka
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Nobue Terakawa
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Akira Oita
- Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Satoshi Yokoyama
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-osaka, Japan.,Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, Higashi-osaka, Japan
| | - Atsushi Kawase
- Department of Pharmacy, Faculty of Pharmacy, Kindai University, Higashi-osaka, Japan
| | - Kouichi Hosomi
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-osaka, Japan.,Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, Higashi-osaka, Japan
| | - Mitsutaka Takada
- Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-osaka, Japan.,Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, Higashi-osaka, Japan
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39
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Aslam S, Rotstein C. Candida infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33:e13623. [PMID: 31155770 DOI: 10.1111/ctr.13623] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 05/29/2019] [Indexed: 12/11/2022]
Abstract
These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice provide recommendations for the diagnosis and management of Candida infections in solid organ transplant recipients. Candida infections manifest primarily as candidemia and invasive candidiasis and cause considerable morbidity and mortality. Early diagnosis and initiation of treatment are necessary to reduce mortality. For both candidemia and invasive candidiasis, an echinocandin is recommended for initial therapy. However, early transition to oral therapy is encouraged when patients are stable and the organism is susceptible. Candida prophylaxis should be targeted for high-risk patients in liver, small bowel, and pancreas transplant recipients. Future research should address which patient groups may benefit most from preventative antifungal therapy strategies.
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Affiliation(s)
- Saima Aslam
- Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California
| | - Coleman Rotstein
- Multi-organ Transplant Program, Division of Infectious Diseases, Department of Medicine, University of Toronto, University Health Network, Toronto, Ontario, Canada
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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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Giannella M, Husain S, Saliba F, Viale P. Use of echinocandin prophylaxis in solid organ transplantation. J Antimicrob Chemother 2019; 73:i51-i59. [PMID: 29304212 DOI: 10.1093/jac/dkx449] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Invasive fungal infections (IFIs) are a major threat to patients undergoing solid organ transplantation (SOT). Owing to improvements in surgical techniques, immunosuppression therapy and antifungal prophylaxis, the incidence of IFIs has been decreasing in recent years. However, IFI-associated morbidity and mortality remain significant. Invasive candidiasis (IC) and aspergillosis (IA) are the main IFIs after SOT. Risk factors for IC and IA continue to evolve, and thus strategies for their prevention should be constantly updated and targeted to both individual patient risk factors and local epidemiology. In this review, we discuss the current epidemiology and risk factors for IFIs in SOT recipients in the context of actual approaches to antifungal prophylaxis, including experience with the use of echinocandins, after SOT.
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Affiliation(s)
- Maddalena Giannella
- Infectious Diseases Unit, Sant'Orsola Malpighi Hospital, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Shahid Husain
- Division of Infectious Diseases, Multi-Organ Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Faouzi Saliba
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - Pierluigi Viale
- Infectious Diseases Unit, Sant'Orsola Malpighi Hospital, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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Manuel O, Ison MG. Prevention and Treatment of Yeast and Endemic Fungal Infections. INFECTIOUS DISEASES IN SOLID-ORGAN TRANSPLANT RECIPIENTS 2019. [PMCID: PMC7138456 DOI: 10.1007/978-3-030-15394-6_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Invasive fungal infections (IFIs) remain an important complication of solid organ transplantation owing to their significant morbidity and mortality and include infections due to Candida, Cryptococcus, endemic mycosis, and other rare yeasts and molds. IFIs occur in different intervals posttransplantation and depend on a number of extrinsic and intrinsic risk factors, some of which are specific to the type of organs transplanted, surgical techniques, and type of immunosuppressive medications. Donor-derived IFIs and emergence of new multidrug-resistant yeasts have been reported in various healthcare settings. Clinical manifestations of yeast and endemic fungal infections vary in different types of organ transplants. Diagnosis of IFIs in SOT recipients is challenging due to their nonspecific signs and symptoms owing to the impaired inflammatory responses as a result of immunosuppression and the lack of highly sensitive and specific diagnostic modalities. Early diagnosis is key to successful therapy, and physicians should have a high index of suspicion based on risk factors and epidemiology of these pathogens. Antifungal treatment strategies for yeast infections have been outlined in various society guidelines. Management of complications that arise before or during antifungal therapy is critical for optimizing clinical response.
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Affiliation(s)
- Oriol Manuel
- Infectious Diseases Service and Transplantation Center, University Hospital of Lausanne, Lausanne, Switzerland
| | - Michael G Ison
- School of Medicine, Northwestern University Feinberg, Chicago, IL USA
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Abstract
Liver transplantation has become an important treatment modality for patients with end-stage liver disease/cirrhosis, acute liver failure, and hepatocellular carcinoma. Although surgical techniques and immunosuppressive regimens for liver transplantation have improved significantly over the past 20 years, infectious complications continue to contribute to the morbidity and mortality in this patient population. The use of standardized screening protocols for both donors and recipients, coupled with targeted prophylaxis against specific pathogens, has helped to mitigate the risk of infection in liver transplant recipients. Patients with chronic liver disease and cirrhosis have immunological deficits that place them at increased risk for infection while awaiting liver transplantation. The patient undergoing liver transplantation is prone to develop healthcare-acquired infections due to multidrug-resistant organisms that could potentially affect patient outcomes after transplantation. The complex nature of liver transplant surgery that involves multiple vascular and hepatobiliary anastomoses further increases the risk of infection after liver transplantation. During the early post-transplantation period, healthcare-acquired bacterial and fungal infections are the most common types of infection encountered in liver transplant recipients. The period of maximal immunosuppression that occurs at 1–6 months after transplantation can be complicated by opportunistic infections due to both primary infection and reactivation of latent infection. Severe community-acquired infections can complicate the course of liver transplantation beyond 12 months after transplant surgery. This chapter provides an overview of liver transplantation including indications, donor-recipient selection criteria, surgical procedures, and immunosuppressive therapies. A focus on infections in patients with chronic liver disease/cirrhosis and an overview of the specific infectious complications in liver transplant recipients are presented.
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Abstract
Invasive candidiasis (IC) remains the most common invasive fungal infection following solid-organ transplant (SOT), but risk factors are evolving. Current challenges include infection due to drug resistant non-albicans and emerging novel species such as Candida auris. Preventive antifungal use in SOT needs to be re-examined in light of these current challenges. Cryptococcosis is the second most common IFI following SOT. Cryptococcus gattii is an emerging pathogen that can have reduced in-vitro susceptibility to antifungal agents. Cryptococcus associated IRIS in SOT is a clinical entity that warrants heightened awareness for timely recognition and management.
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Affiliation(s)
- Sarah Taimur
- Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, One-Gustave L. Levy Place, New York, NY 10029, USA.
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45
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Al Jishi Y, Rotstein C, Kumar D, Humar A, Singer LG, Keshavjee S, Husain S. Echinocandin use in lung transplant recipients. Clin Transplant 2018; 32:e13437. [PMID: 30375050 DOI: 10.1111/ctr.13437] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Revised: 10/12/2018] [Accepted: 10/22/2018] [Indexed: 01/01/2023]
Abstract
BACKGROUND Invasive fungal infections (IFI) are associated with significant morbidity and mortality in lung transplant recipients (LTRs). However, data outlining use of echinocandins in prophylaxis and therapy of LTRs are limited. METHOD A single-center retrospective cohort study on all LTRs from January-2010 to December-2016. Participants were screened for antifungal use to assess rate, tolerability, and clinical outcome of echinocandin use in LTRs, during the first 6 weeks of posttransplant. RESULTS A total of 777 lung transplants were reviewed in 763 LTRs. Antifungals were administered to 268 (35%) of LTRs. Reasons included preemptive antifungal therapy (55% [149/268]), targeted antifungal prophylaxis (34% [92/268]), and definitive IFI therapy (10% [27/268]). Azoles were first-line agents in 80% (215/268) of LTRs, caspofungin in 11% (30/268), micafungin in 6.7% (18/268), amphotericin B in 1.5% (4/268), and anidulafungin in 0.4% (1/268]). LTRs were started on echinocandins due to abnormal liver enzymes in 91% (46/49). Overall, 23% (50/215) of LTR's were switched off azoles. Of these, 54% (27/50) were switched to echinocandins. Switch from azoles to echinocandin was undertaken due to abnormal liver enzymes in 63% (17/27). No patients receiving first-line echinocandins were switched to other therapies due to adverse events. CONCLUSIONS Our data suggest that echinocandins are utilized in approximately 18.3% of lung transplant recipients. They are the preferred second-line agents due to a lower adverse-effect profile compared to the azoles.
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Affiliation(s)
- Yamama Al Jishi
- Department of Medicine, Division of Infectious Diseases and Toronto Lung Transplant Program, University of Toronto, Toronto, Ontario, Canada.,Division of Infectious Diseases, Department of Medicine, University of Toronto, University Health Network, Toronto, Ontario, Canada
| | - Coleman Rotstein
- Division of Infectious Diseases, Department of Medicine, University of Toronto, University Health Network, Toronto, Ontario, Canada.,Multi-Organ Transplant Program, University of Toronto, University Health Network, Toronto, Ontario, Canada
| | - Deepali Kumar
- Division of Infectious Diseases, Department of Medicine, University of Toronto, University Health Network, Toronto, Ontario, Canada.,Multi-Organ Transplant Program, University of Toronto, University Health Network, Toronto, Ontario, Canada
| | - Atul Humar
- Division of Infectious Diseases, Department of Medicine, University of Toronto, University Health Network, Toronto, Ontario, Canada.,Multi-Organ Transplant Program, University of Toronto, University Health Network, Toronto, Ontario, Canada
| | - Lianne G Singer
- Multi-Organ Transplant Program, University of Toronto, University Health Network, Toronto, Ontario, Canada.,Division of Respirology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Shaf Keshavjee
- Multi-Organ Transplant Program, University of Toronto, University Health Network, Toronto, Ontario, Canada.,Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute and Division of Thoracic Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Shahid Husain
- Division of Infectious Diseases, Department of Medicine, University of Toronto, University Health Network, Toronto, Ontario, Canada.,Multi-Organ Transplant Program, University of Toronto, University Health Network, Toronto, Ontario, Canada
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46
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Swaminathan S, Kamat S, Pinto NA. Echinocandins: Their role in the management of Candida biofilms. Indian J Med Microbiol 2018; 36:87-92. [PMID: 29735833 DOI: 10.4103/ijmm.ijmm_17_400] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The importance of antifungal agents and their clinical implications has received little attention in comparison to antibiotics, particularly in the health-care setting. However, apart from bacterial infections rising in hospitals, the incidences of fungal infections are growing with the development of resistance to conventional antifungal agents. Newer antifungal agents such as echinocandins (ECs) have been extensively studied over the past decade and are recognised as a superior treatment compared with prior antifungals as a first line of therapy in tertiary institutions. Caspofungin (CAS), micafungin (MICA) and anidulafungin (ANID) are the three most widely used EC antifungal agents. The treatment of biofilm-associated fungal infections affecting patients in tertiary health-care facilities has been identified as a challenge, particularly in Indian Intensive Care Unit (ICU) settings. With the rising number of critically ill patients requiring invasive devices such as central venous catheters for treatment, especially in ICUs, these devices serve as a potential source of nosocomial infections. Candida spp. colonisation is a major precursor of these infections and further complicates and prolongs treatment procedures, adding to increasing costs both for hospitals and the patient. Analysing studies involving the use of these agents can help in making critical decisions for antifungal therapy in the event of a fungal infection in the ICU. In addition, the development of resistance to antifungal agents is a crucial factor for assessing the appropriate antifungals that can be used for treatment. This review provides an overview of ANID in biofilms, along with CAS and MICA, in terms of clinical efficacy, resistance development and potency, primarily against Candida spp.
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Affiliation(s)
| | - Shweta Kamat
- Medical Affairs, Pfizer Ltd., Mumbai, Maharashtra, India
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47
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Deziel PJ, Razonable R. Anti-infective chemoprophylaxis after solid-organ transplantation. Expert Rev Clin Immunol 2018; 14:469-479. [PMID: 29764228 DOI: 10.1080/1744666x.2018.1476852] [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] [Indexed: 10/16/2022]
Abstract
INTRODUCTION Solid organ transplant (SOT) recipients are at high risk of opportunistic infections due to bacterial, viral, fungal, and parasitic pathogens. Anti-infective prophylaxis is a time-tested proven strategy for the prevention of these infections after SOT. Areas covered: The current recommendations for the prevention of surgical site infections, herpes simplex, cytomegalovirus, invasive fungal infections, and selected parasitic diseases are highlighted. Recent peer-reviewed publications on the prevention of infection after SOT were reviewed and their significance was discussed in the context of the current recommendations for preventing infectious complications. Expert commentary: The authors comment on the current approaches to infection prevention in transplant recipients, and discuss how these recommendations are implemented in their clinical practice. Notable findings published during the past year were highlighted, and their clinical significance was interpreted in the context of current recommendations. The evolution of diagnostic and immunologic assays was emphasized, with focus on their potential role in optimizing the current antimicrobial approaches to infection prevention after SOT.
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Affiliation(s)
- Paul J Deziel
- a Division of Infectious Diseases, The William J von Liebig Center for Transplantation and Clinical Regeneration , Mayo Clinic College of Medicine and Science, Mayo Clinic , Rochester , MN , USA
| | - Raymund Razonable
- a Division of Infectious Diseases, The William J von Liebig Center for Transplantation and Clinical Regeneration , Mayo Clinic College of Medicine and Science, Mayo Clinic , Rochester , MN , USA
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48
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Neofytos D, Chatzis O, Nasioudis D, Boely Janke E, Doco Lecompte T, Garzoni C, Berger C, Cussini A, Boggian K, Khanna N, Manuel O, Mueller NJ, van Delden C. Epidemiology, risk factors and outcomes of invasive aspergillosis in solid organ transplant recipients in the Swiss Transplant Cohort Study. Transpl Infect Dis 2018; 20:e12898. [PMID: 29668068 DOI: 10.1111/tid.12898] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 03/07/2018] [Accepted: 03/07/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND There is lack of recent multicenter epidemiological data on invasive aspergillosis (IA) among solid organ transplant recipient (SOTr) in the mold-acting antifungal era. We describe the epidemiology and outcomes of IA in a contemporary cohort of SOTr using the Swiss Transplant Cohort Study. METHODS All consecutive SOTr with proven or probable IA between 01.05.2008 and 31.12.2014 were included. A case-control study to identify IA predictors was performed: 1-case was matched with 3-controls based on SOT type, transplant center, and time post-SOT. RESULTS Among 2868 SOTr, 70 (2.4%) patients were diagnosed with proven (N: 30/70, 42.9%) or probable (N: 40/70, 57.1%) IA. The incidence of IA was 8.3%, 7.1%, 2.6%, 1.3%, and 1.2% in lung, heart, combined, kidney, and liver transplant recipients, respectively, Galactomannan immunoassay was positive in 1/3 of patients tested. Only 33/63 (52.4%) of patients presented with typical pulmonary radiographic findings. Predictors of IA included: renal insufficiency, re-operation, and bacterial and viral infections. 12-week mortality was higher in liver (85.7%, 6/7) compared to other (15.9%, 10/63; P < .001) SOTr. CONCLUSIONS Invasive aspergillosis remains a rare complication post-SOT, with atypical radiographic presentations and low positivity rates of biomarkers posing significant diagnostic challenges. Although overall mortality has decreased in SOTr, it remains high in liver SOTr.
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Affiliation(s)
- D Neofytos
- Transplant Infectious Diseases Unit, University Hospitals of Geneva, Geneva, Switzerland
| | - O Chatzis
- Transplant Infectious Diseases Unit, University Hospitals of Geneva, Geneva, Switzerland.,Division of Pediatric Infectious Diseases, University Hospital of St Luc, Brussels, Belgium
| | - D Nasioudis
- Transplant Infectious Diseases Unit, University Hospitals of Geneva, Geneva, Switzerland
| | - E Boely Janke
- Transplant Infectious Diseases Unit, University Hospitals of Geneva, Geneva, Switzerland
| | - T Doco Lecompte
- Transplant Infectious Diseases Unit, University Hospitals of Geneva, Geneva, Switzerland
| | - C Garzoni
- Department of Infectious Diseases, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.,Departments of Internal Medicine and Infectious Disease, Clinica Luganese, Lugano, Switzerland
| | - C Berger
- Division of Infectious Diseases and Hospital Epidemiology, University Children's Hospital Zürich, Zürich, Switzerland
| | - A Cussini
- Department of Infectious Diseases, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - K Boggian
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St Gallen, St Gallen, Switzerland
| | - N Khanna
- Division of Infectious Diseases and Hospital Epidemiology, University and University Hospital of Basel, Basel, Switzerland
| | - O Manuel
- Service of Infectious Diseases and Transplantation Center, University Hospital of Lausanne, Lausanne, Switzerland
| | - N J Mueller
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland
| | - C van Delden
- Transplant Infectious Diseases Unit, University Hospitals of Geneva, Geneva, Switzerland
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49
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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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50
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Lavezzo B, Patrono D, Tandoi F, Martini S, Fop F, Ballerini V, Stratta C, Skurzak S, Lupo F, Strignano P, Donadio PP, Salizzoni M, Romagnoli R, De Rosa FG. A simplified regimen of targeted antifungal prophylaxis in liver transplant recipients: A single-center experience. Transpl Infect Dis 2018; 20:e12859. [PMID: 29427394 DOI: 10.1111/tid.12859] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2017] [Revised: 09/17/2017] [Accepted: 11/12/2017] [Indexed: 12/30/2022]
Abstract
BACKGROUND Invasive fungal infection (IFI) is a severe complication of liver transplantation burdened by high mortality. Guidelines recommend targeted rather than universal antifungal prophylaxis based on tiers of risk. METHODS We aimed to evaluate IFI incidence, risk factors, and outcome after implementation of a simplified two-tiered targeted prophylaxis regimen based on a single broad-spectrum antifungal drug (amphotericin B). Patients presenting 1 or more risk factors according to literature were administered prophylaxis. Prospectively collected data on all adult patients transplanted in Turin from January 2011 to December 2015 were reviewed. RESULTS Patients re-transplanted before postoperative day 7 were considered once, yielding a study cohort of 581 cases. Prophylaxis was administered to 299 (51.4%) patients; adherence to protocol was 94.1%. Sixteen patients developed 18 IFIs for an overall rate of 2.8%. All IFI cases were in targeted prophylaxis group; none of the non-prophylaxis group developed IFI. Most cases (81.3%) presented within 30 days after transplantation during prophylaxis; predominant pathogens were molds (94.4%). Only 1 case of candidemia was observed. One-year mortality in IFI patients was 33.3% vs 6.4% in patients without IFI (P = .001); IFI attributable mortality was 6.3%. At multivariate analysis, significant risk factors for IFI were renal replacement therapy (OR = 8.1) and re-operation (OR = 5.2). CONCLUSIONS The implementation of a simplified targeted prophylaxis regimen appeared to be safe and applicable and was associated with low IFI incidence and mortality. Association of IFI with re-operation and renal replacement therapy calls for further studies to identify optimal prophylaxis in this subset of patients.
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Affiliation(s)
- B Lavezzo
- Anesthesia and Intensive Care Unit 2, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - D Patrono
- Liver Transplant Center, General Surgery 2U, University of Torino, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - F Tandoi
- Liver Transplant Center, General Surgery 2U, University of Torino, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - S Martini
- Gastrohepatology Unit, AOU Città della Salute e della Scienza, Torino, Italy
| | - F Fop
- Nephrology, Dialysis and Transplantation Unit, University of Torino, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - V Ballerini
- Anesthesia and Intensive Care Unit 2, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - C Stratta
- Anesthesia and Intensive Care Unit 2, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - S Skurzak
- Anesthesia and Intensive Care Unit 2, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - F Lupo
- Liver Transplant Center, General Surgery 2U, University of Torino, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - P Strignano
- Liver Transplant Center, General Surgery 2U, University of Torino, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - P P Donadio
- Anesthesia and Intensive Care Unit 2, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - M Salizzoni
- Liver Transplant Center, General Surgery 2U, University of Torino, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - R Romagnoli
- Liver Transplant Center, General Surgery 2U, University of Torino, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - F G De Rosa
- Department of Medical Sciences, Infectious Diseases, University of Torino, A.O.U. Città della Salute e della Scienza, Torino, Italy
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