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Bussini L, Bartoletti M, Bassetti M, Cortegiani A, De Pascale G, De Rosa FG, Falcone M, Giannella M, Girardis M, Grossi P, Mikulska M, Navalesi P, Pea F, Sanguinetti M, Tascini C, Viaggi B, Viale P. Role of liposomal amphotericin B in intensive care unit: an expert opinion paper. JOURNAL OF ANESTHESIA, ANALGESIA AND CRITICAL CARE 2025; 5:23. [PMID: 40301956 PMCID: PMC12042420 DOI: 10.1186/s44158-025-00236-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Accepted: 03/16/2025] [Indexed: 05/01/2025]
Abstract
INTRODUCTION Invasive fungal infections (IFI) are frequent in patients admitted to the intensive care unit (ICU). The use of first-line antifungals like triazoles or echinocandins may be limited by the global spread of multi-drug resistance species, drug-drug interactions, low organ penetration, and some safety concerns in case of multi-organ failure. Liposomal amphotericin B (L-AmB) is a polyene drug with a broad activity against mold and yeast and an acceptable safety profile. To outline the role of L-AmB in the treatment of IFI in critically ill patients, a panel of experts was invited to draw up an expert opinion paper on the appropriate place in therapy of L-AmB in different clinical scenarios of patients admitted to ICU. METHODS A multidisciplinary group of 16 specialists in infectious disease, microbiology, pharmacology, and intensive care elaborated an expert opinion document through a multi-step approach: (1) the scientific panel defined the items and wrote the statements on the management of IFI in ICU, (2) a survey was submitted to an external panel to express agreement or disagreement on the statements, and (3) the panel reviewed the survey and implemented the final document. RESULTS The final document included 35 statements that focused on epidemiology and microbiological rationale of the use of systemic L-AmB in critically ill patients and its potential role in specific clinical scenarios in the ICU. CONCLUSION Systemic L-AmB may represent an appropriate therapeutic choice for IFI in ICU patients with different underlying conditions, especially when the use of first-line agents is undermined. This expert opinion paper may provide a useful guide for clinicians.
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Affiliation(s)
- Linda Bussini
- Infectious Diseases Unit, Hospital Health Direction, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072, Milan, Italy
| | - Michele Bartoletti
- Infectious Diseases Unit, Hospital Health Direction, IRCCS Humanitas Research Hospital, 20089, Rozzano, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072, Milan, Italy
| | - Matteo Bassetti
- Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Division of Infectious Diseases, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
| | - Andrea Cortegiani
- Department of Precision Medicine in Medical Surgical and Critical Care, University of Palermo, Palermo, Italy
- Department of Anesthesia, Intensive Care and Emergency Policlinico Paolo Giaccone, University of Palermo, Palermo, Italy
| | - Gennaro De Pascale
- Department of Emergency, Intensive Care Medicine and Anaesthesia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | | | - Marco Falcone
- Infectious Disease Unit, AOU Pisana PO Cisanello, University of Pisa, Pisa, 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
| | - Massimo Girardis
- Anesthesia and Intensive Care Medicine, Policlinico Di Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Paolo Grossi
- Infectious and Tropical Diseases Unit, Department of Medicine and Surgery, University of Insubria - ASST-Sette Laghi, Varese, Italy
| | - Malgorzata Mikulska
- Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
- Division of Infectious Diseases, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
| | - Paolo Navalesi
- Institute of Anesthesia and Intensive Care, University of Padua, Padua, Italy
| | - Federico Pea
- Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy
- Clinical Pharmacology Unit, IRCCS Azienda Ospedaliero Universitaria Di Bologna, Bologna, Italy
| | - Maurizio Sanguinetti
- Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of the Sacred Heart, Rome, Italy
| | - Carlo Tascini
- Infectious Diseases Clinic, Azienda Sanitaria Universitaria del Friuli Centrale (ASUFC), Udine, Italy
| | - Bruno Viaggi
- ICU Department, Careggi Hospital, Florence, 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.
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Herrera S, Magyar U, Husain S. Invasive Aspergillosis in the Current Era. Infect Dis Clin North Am 2025; 39:e33-e60. [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] [MESH Headings] [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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Long C, Peng W, Zhao J, Wan Q. The Influence of Invasive Candida Infections on Prognosis and Analysis of Their Risk Factors After Liver Transplantation. Clin Ther 2024; 46:1041-1048. [PMID: 39368880 DOI: 10.1016/j.clinthera.2024.09.012] [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: 02/26/2024] [Revised: 08/24/2024] [Accepted: 09/08/2024] [Indexed: 10/07/2024]
Abstract
PURPOSE This study aimed to investigate the incidence, timing, risk factors, and impacts of invasive Candida infections (ICIs) within 3 months after liver transplantation (LT) on LT recipients' prognosis. METHODS Patients undergoing LT from January 2015 to December 2022 in a tertiary university hospital were investigated the incidence, onset, and risk factors of ICIs and the effects of ICIs on the outcome of LT recipients using statistical methods. FINDINGS The mean age of involved 389 LT recipients was 47.3 ± 10.5 years, with 322 (82.8%) being men. The incidence of ICIs was 3.3% (13/389), and the median time between LT and onset of ICIs was 5.0 days. The univariate analysis of predictors of ICIs identified that massive blood loss, prolonged duration of central line and urethral catheter, and prophylactic antifungal therapy were related to post-LT ICI risk. Multivariate logistic regression analysis adjusted for men and age identified that intraoperative blood loss ≥5000 mL (odds ratio [OR] = 7.005, 95% CI: 2.084-23.542, P = 0.002) and central line duration >14 days (OR = 5.270, 95% CI: 1.556-17.854, P = 0.008) were independently associated with the development of post-LT ICIs. Post-LT prophylactic antifungal therapy >3 days reduced ICIs (OR = 0.103, 95% CI: 0.021-0.501, P = 0.005). Regarding clinical outcomes, patients with ICIs were more likely to stay in the intensive care unit for 7 days or longer compared with those without ICIs (OR = 6.910, 95% CI: 1.737-27.493, P = 0.006). ICIs had no impact on hospitalization stay and 1-month all-cause mortality after LT. IMPLICATIONS ICIs are frequent and occur early after LT. Predictors of post-LT ICIs were massive intraoperative blood loss and prolonged duration of the central line. However, post-LT prophylactic antifungal therapy reduced ICIs. Patients with ICIs stayed longer in the intensive care unit than those without ICIs.
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Affiliation(s)
- Chunjiao Long
- Department of Nephrology, the Third Xiangya Hospital of Central South University, Changsha, China
| | - Weiting Peng
- The Second Affiliated Hospital Class, Grade 2019, 8-Year Clinical Medicine Program, Xiangya School of Medicine, Central South University, Changsha, China
| | - Jie Zhao
- Department of Liver Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Qiquan Wan
- Department of Transplant Surgery, the Third Xiangya Hospital of Central South University, Changsha, China; Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, the Third Xiangya Hospital of Central South University, Changsha, China.
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Bredehoeft CT, Sarwar S, Marschalk N. Simultaneous invasive aspergillosis and mucormycosis after orthotopic liver transplant. Transpl Infect Dis 2024; 26:e14381. [PMID: 39340387 DOI: 10.1111/tid.14381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024]
Affiliation(s)
- Cole T Bredehoeft
- Department of Internal Medicine, Division of Infectious Diseases, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Sajed Sarwar
- Department of Internal Medicine, Division of Infectious Diseases, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Nicholas Marschalk
- Department of Internal Medicine, Division of Infectious Diseases, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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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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Jiang J, Peng P, Wan Q. The predictors of fungal infections after liver transplantation and the influence of fungal infections on outcomes. Clin Exp Med 2024; 24:144. [PMID: 38960977 PMCID: PMC11222231 DOI: 10.1007/s10238-024-01419-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 06/24/2024] [Indexed: 07/05/2024]
Abstract
The primary objective of this study was to assess the incidence, timing, risk factors of fungal infections (FIs) within 3 months after liver transplantation (LT). The secondary objective was to evaluate the impact of FIs on outcomes. Four hundred and ten patients undergoing LT from January 2015 until January 2023 in a tertiary university hospital were included in the present retrospective cohort study to investigate the risk factors of FIs and to assess the impacts of FIs on the prognosis of LT recipients using logistic regression. The incidence of FIs was 12.4% (51/410), and median time from LT to the onset of FIs was 3 days. By univariate analysis, advanced recipient age, prolonged hospital stay prior to LT, high Model for End Stage Liver Disease (MELD) score, use of broad-spectrum antibiotics, and elevated white blood cell (WBC) count, increased operating time, massive blood loss and red blood cell transfusion, elevated alanine aminotransferase on day 1 and creatinine on day 3 after LT, prolonged duration of urethral catheter, prophylactic antifungal therapy, the need for mechanical ventilation and renal replacement therapy were identified as factors of increased post-LT FIs risk. Multivariate logistic regression analysis identified that recipient age ≥ 55 years[OR = 2.669, 95%CI: 1.292-5.513, P = 0.008], MELD score at LT ≥ 22[OR = 2.747, 95%CI: 1.274-5.922, P = 0.010], pre-LT WBC count ≥ 10 × 109/L[OR = 2.522, 95%CI: 1.117-5.692, P = 0.026], intraoperative blood loss ≥ 3000 ml [OR = 2.691, 95%CI: 1.262-5.738, P = 0.010], post-LT duration of urethral catheter > 4 d [OR = 3.202, 95%CI: 1.553-6.602, P = 0.002], and post-LT renal replacement therapy [OR = 5.768, 95%CI: 1.822-18.263, P = 0.003] were independently associated with the development of post-LT FIs. Post-LT prophylactic antifungal therapy ≥ 3 days was associated with a lower risk of the development of FIs [OR = 0.157, 95%CI: 0.073-0.340, P < 0.001]. As for clinical outcomes, FIs had a negative impact on intensive care unit (ICU) length of stay ≥ 7 days than those without FIs [OR = 3.027, 95% CI: 1.558-5.878, P = 0.001] but had no impact on hospital length of stay and 1-month all-cause mortality after LT. FIs are frequent complications after LT and the interval between the onset of FIs and LT was short. Risk factors for post-LT FIs included high MELD score at LT, advanced recipient age, pre-LT WBC count, massive intraoperative blood loss, prolonged post-LT duration of urethral catheter, and the need for post-LT renal replacement therapy. However, post-LT prophylactic antifungal therapy was independently associated with the reduction in the risk of FIs. FIs had a significant negative impact on ICU length of stay.
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Affiliation(s)
- Juan Jiang
- Department of Nephrology, The Third Xiangya Hospital of Central South University, Changsha, 410013, China
| | - Peng Peng
- Clinical Laboratory Medicine Center, Xiangya Hospital Zhuzhou of Central South University, Zhuzhou, 421007, China
| | - Qiquan Wan
- Department of Transplant Surgery, The Third Xiangya Hospital of Central South University, Changsha, 410013, China.
- Engineering and Technology Research Center for Transplantation Medicine of National Health Commission, The Third Xiangya Hospital of Central South University, Changsha, 410013, China.
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Elhaj Mahmoud D, Hérivaux A, Morio F, Briard B, Vigneau C, Desoubeaux G, Bouchara JP, Gangneux JP, Nevez G, Le Gal S, Papon N. The epidemiology of invasive fungal infections in transplant recipients. Biomed J 2024; 47:100719. [PMID: 38580051 PMCID: PMC11220536 DOI: 10.1016/j.bj.2024.100719] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 03/21/2024] [Accepted: 03/24/2024] [Indexed: 04/07/2024] Open
Abstract
Transplant patients, including solid-organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, are exposed to various types of complications, particularly rejection. To prevent these outcomes, transplant recipients commonly receive long-term immunosuppressive regimens that in turn make them more susceptible to a wide array of infectious diseases, notably those caused by opportunistic pathogens. Among these, invasive fungal infections (IFIs) remain a major cause of mortality and morbidity in both SOT and HSCT recipients. Despite the continuing improvement in early diagnostics and treatments of IFIs, the management of these infections in transplant patients is still complicated. Here, we provide an overview concerning the most recent trends in the epidemiology of IFIs in SOT and HSCT recipients by describing the prominent yeast and mold species involved, the timing of post-transplant IFIs and the risk factors associated with their occurrence in these particularly weak populations. We also give special emphasis into basic research advances in the field that recently suggested a role of the global and long-term prophylactic regimen in orchestrating various biological disturbances in the organism and conditioning the emergence of the most adapted fungal strains to the particular physiological profiles of transplant patients.
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Affiliation(s)
- Dorra Elhaj Mahmoud
- University of Angers, University of Brest, Infections Respiratoires Fongiques, SFR Interactions Cellulaires et Applications Thérapeutiques, Angers, France
| | - Anaïs Hérivaux
- University of Angers, University of Brest, Infections Respiratoires Fongiques, SFR Interactions Cellulaires et Applications Thérapeutiques, Angers, France
| | - Florent Morio
- Nantes Université, CHU Nantes, Cibles et Médicaments des Infections et de L'Immunité, UR1155, Nantes, France
| | - Benoit Briard
- INSERM, Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100, Université de Tours, Faculté de Médecine de Tours, Tours, France; CHRU Tours, Parasitologie-Mycologie Médicale-Médecine Tropicale, Tours, France
| | - Cécile Vigneau
- University of Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail), UMR_S, 1085, Rennes, France; Division of Nephrology, Rennes University Hospital, Rennes, France
| | - Guillaume Desoubeaux
- INSERM, Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100, Université de Tours, Faculté de Médecine de Tours, Tours, France; CHRU Tours, Parasitologie-Mycologie Médicale-Médecine Tropicale, Tours, France
| | - Jean-Philippe Bouchara
- University of Angers, University of Brest, Infections Respiratoires Fongiques, SFR Interactions Cellulaires et Applications Thérapeutiques, Angers, France
| | - Jean-Pierre Gangneux
- University of Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail), UMR_S, 1085, Rennes, France; Laboratory of Parasitology and Medical Mycology, European Confederation of Medical Mycology (ECMM) Excellence Center, Centre National de Référence Aspergilloses Chroniques, Rennes University Hospital, Rennes, France
| | - Gilles Nevez
- Laboratory of Parasitology and Mycology, Brest University Hospital, Brest, France; University of Brest, University of Angers, Infections Respiratoires Fongiques, SFR Interactions Cellulaires et Applications Thérapeutiques, Brest, France
| | - Solène Le Gal
- Laboratory of Parasitology and Mycology, Brest University Hospital, Brest, France; University of Brest, University of Angers, Infections Respiratoires Fongiques, SFR Interactions Cellulaires et Applications Thérapeutiques, Brest, France
| | - Nicolas Papon
- University of Angers, University of Brest, Infections Respiratoires Fongiques, SFR Interactions Cellulaires et Applications Thérapeutiques, Angers, France.
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Wang W, Wang Y, Zhang Y, Zhang W, Bai X, Zhang Q, Liang T. Universal antifungal prophylaxis effectively prevents fungal bloodstream infection in pediatric liver transplant recipients: a retrospective real-world study. Int J Infect Dis 2024; 143:107003. [PMID: 38521451 DOI: 10.1016/j.ijid.2024.107003] [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: 01/11/2024] [Revised: 02/20/2024] [Accepted: 03/07/2024] [Indexed: 03/25/2024] Open
Abstract
OBJECTIVES Fungal bloodstream infection (fBSI) following pediatric liver transplantation presents a significant challenge; however, there remains a paucity of guidance regarding antifungal prophylaxis in this population. This study aimed to evaluate the effectiveness of universal antifungal prophylaxis and propose a desirable strategy. METHODS We enrolled 604 pediatric patients who underwent liver transplantation between 2020 and 2023, including 242 patients with empirical prophylaxis and 362 patients with universal prophylaxis. Univariate and multivariate logistic regression analyses were performed to identify independent factors for fBSI. RESULTS Eight (2.2%) pediatric recipients in the universal prophylaxis group and 13 (5.4%) in the empirical group developed fBSI (P = 0.038). Universal prophylaxis was a protective factor (P = 0.044), while high-volume intraoperative plasma transfusion and deceased donor liver transplantation were independent risk factors for fBSI (P = 0.035 and 0.008, respectively). Universal antifungal strategy showed an increased overall survival trend after liver transplantation although without significant statistical difference (P = 0.217). Patients with fBSI had poorer survival than those without fBSI (P <0.001). CONCLUSIONS Universal prophylaxis strategy for fBSI in pediatrics after liver transplantation is desirable as it could markedly decrease the occurrence of fBSI. Pediatric patients with deceased donors and high-volume intraoperative transfusion should be paid more attention to preventing fBSI.
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Affiliation(s)
- Weili Wang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yangyang Wang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yuntao Zhang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wei Zhang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
| | - Qi Zhang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China.
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9
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Amjad W, Hamaad Rahman S, Schiano TD, Jafri SM. Epidemiology and Management of Infections in Liver Transplant Recipients. Surg Infect (Larchmt) 2024; 25:272-290. [PMID: 38700753 DOI: 10.1089/sur.2023.346] [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] [Indexed: 07/13/2024] Open
Abstract
Background: Improvements in liver transplant (LT) outcomes are attributed to advances in surgical techniques, use of potent immunosuppressants, and rigorous pre-LT testing. Despite these improvements, post-LT infections remain the most common complication in this population. Bacteria constitute the most common infectious agents, while fungal and viral infections are also frequently encountered. Multi-drug-resistant bacterial infections develop because of polymicrobial overuse and prolonged hospital stays. Immediate post-LT infections are commonly caused by viruses. Conclusions: Appropriate vaccination, screening of both donor and recipients before LT and antiviral prophylaxis in high-risk individuals are recommended. Antimicrobial drug resistance is common in high-risk LT and associated with poor outcomes; epidemiology and management of these cases is discussed. Additionally, we also discuss the effect of coronavirus disease 2019 (COVID-19) infection and monkeypox in the LT population.
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Affiliation(s)
- Waseem Amjad
- Gastroenterology and Hepatology, University of Maryland, Baltimore, Maryland, USA
| | | | - Thomas D Schiano
- Recanati-Miller Transplantation Institute, Division of Liver Diseases, Mount Sinai Medical Center, New York, New York, USA
| | - Syed-Mohammed Jafri
- Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, Michigan, USA
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10
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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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11
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Pennington KM, Martin MJ, Murad MH, Sanborn D, Saddoughi SA, Gerberi D, Peters SG, Razonable RR, Kennedy CC. Risk Factors for Early Fungal Disease in Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis. Transplantation 2024; 108:970-984. [PMID: 37953478 DOI: 10.1097/tp.0000000000004871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2023]
Abstract
BACKGROUND Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant. METHODS We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant. RESULTS We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis. CONCLUSIONS Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both.
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Affiliation(s)
- Kelly M Pennington
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
| | - Max J Martin
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
| | - M Hassan Murad
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - David Sanborn
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
| | | | | | - Steve G Peters
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
| | - Raymund R Razonable
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
- Division of Public Health, Infectious Diseases and Occupational Medicine, Mayo Clinic, Rochester, MN
| | - Cassie C Kennedy
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
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12
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Chadha R, Sakai T, Rajakumar A, Shingina A, Yoon U, Patel D, Spiro M, Bhangui P, Sun LY, Humar A, Bezinover D, Findlay J, Saigal S, Singh S, Yi NJ, Rodriguez-Davalos M, Kumar L, Kumaran V, Agarwal S, Berlakovich G, Egawa H, Lerut J, Clemens Broering D, Berenguer M, Cattral M, Clavien PA, Chen CL, Shah S, Zhu ZJ, Ascher N, Bhangui P, Rammohan A, Emond J, Rela M. Anesthesia and Critical Care for the Prediction and Prevention for Small-for-size Syndrome: Guidelines from the ILTS-iLDLT-LTSI Consensus Conference. Transplantation 2023; 107:2216-2225. [PMID: 37749811 DOI: 10.1097/tp.0000000000004803] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/27/2023]
Abstract
BACKGROUND During the perioperative period of living donor liver transplantation, anesthesiologists and intensivists may encounter patients in receipt of small grafts that puts them at risk of developing small for size syndrome (SFSS). METHODS A scientific committee (106 members from 21 countries) performed an extensive literature review on aspects of SFSS with proposed recommendations. Recommendations underwent a blinded review by an independent expert panel and discussion/voting on the recommendations occurred at a consensus conference organized by the International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplantation Society of India. RESULTS It was determined that centers with experience in living donor liver transplantation should utilize potential small for size grafts. Higher risk recipients with sarcopenia, cardiopulmonary, and renal dysfunction should receive small for size grafts with caution. In the intraoperative phase, a restrictive fluid strategy should be considered along with routine use of cardiac output monitoring, as well as use of pharmacologic portal flow modulation when appropriate. Postoperatively, these patients can be considered for enhanced recovery and should receive proactive monitoring for SFSS, nutrition optimization, infection prevention, and consideration for early renal replacement therapy for avoidance of graft congestion. CONCLUSIONS Our recommendations provide a framework for the optimal anesthetic and critical care management in the perioperative period for patients with grafts that put them at risk of developing SFSS. There is a significant limitation in the level of evidence for most recommendations. This statement aims to provide guidance for future research in the perioperative management of SFSS.
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Affiliation(s)
- Ryan Chadha
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL
| | - Tetsuro Sakai
- Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Akila Rajakumar
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Alexandra Shingina
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN
| | - Uzung Yoon
- Department of Anesthesiology, Thomas Jefferson University Hospital, Philadelphia, PA
| | - Dhupal Patel
- Department of Anesthesia and Intensive Care Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Michael Spiro
- Department of Anaesthesia, Royal Devon and Exeter and Department of Anaesthesia and Intensive Care Medicine, The Royal Free Hospital, London, United Kingdom
| | - Pooja Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Delhi, NCR, India
| | - Li-Ying Sun
- Department of Critical Liver Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Abhinav Humar
- Division of Transplantation, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Dmitri Bezinover
- Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA
| | - James Findlay
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Sanjiv Saigal
- Centre of Liver and Biliary Sciences, Centre of Gastroenterology, Hepatology and Endoscopy, Max Super Specialty Hospital, New Delhi, India
| | - Shweta Singh
- Department of Anesthesiology and Critical Care, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Nam-Joon Yi
- Division of HBP Surgery, Department of Surgery, Seoul National University, College of Medicine, Seoul, Korea
| | - Manuel Rodriguez-Davalos
- Division of Transplantation and Advanced Hepatobiliary Surgery, University of Utah, Primary Children's Hospital, Salt Lake City, UT
| | - Lakshmi Kumar
- Department of Anesthesiology, Amrita Hospital, Kochi, India
| | - Vinay Kumaran
- Division of Transplant Surgery, Department of Surgery, VCU Medical Center, Richmond, VA
| | - Shaleen Agarwal
- Centre of Liver and Biliary Sciences, Centre of Gastroenterology, Hepatology and Endoscopy, Max Super Specialty Hospital, New Delhi, India
| | | | - Hiroto Egawa
- Department of Surgery, Tokyo Women's Medical University, Tokyo, Japan
| | - Jan Lerut
- Cliniques Universitaires Saint-Luc, Brussels, Belgium
| | - Dieter Clemens Broering
- Organ Transplant Center of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Marina Berenguer
- Liver Transplantation and Hepatology Unit, La Fe University Hospital and IISLaFe and Ciberehd, Valencia, Spain
| | - Mark Cattral
- Ajmera Transplant Center, University of Toronto, Toronto, ON, Canada
| | | | - Chao-Long Chen
- Liver Transplantation Centre, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Samir Shah
- Department of Hepatology, Institute of Liver Disease, HPB Surgery and Transplant, Global Hospitals, Mumbai, India
| | - Zhi-Jun Zhu
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China
| | - Nancy Ascher
- Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Delhi, NCR, India
| | - Ashwin Rammohan
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Jean Emond
- Liver and Abdominal Transplant Surgery, Columbia University Irving Medical Center, New York, NY
| | - Mohamed Rela
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
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13
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Badrane H, Cheng S, Dupont CL, Hao B, Driscoll E, Morder K, Liu G, Newbrough A, Fleres G, Kaul D, Espinoza JL, Clancy CJ, Nguyen MH. Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures. Nat Commun 2023; 14:5918. [PMID: 37739935 PMCID: PMC10516878 DOI: 10.1038/s41467-023-41509-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 09/07/2023] [Indexed: 09/24/2023] Open
Abstract
The longstanding model is that most bloodstream infections (BSIs) are caused by a single organism. We perform whole genome sequencing of five-to-ten strains from blood culture (BC) bottles in each of ten patients with Candida glabrata BSI. We demonstrate that BCs contain mixed populations of clonal but genetically diverse strains. Genetically distinct strains from two patients exhibit phenotypes that are potentially important during BSIs, including differences in susceptibility to antifungal agents and phagocytosis. In both patients, the clinical microbiology lab recovered a fluconazole-susceptible index strain, but we identify mixed fluconazole-susceptible and -resistant populations. Diversity in drug susceptibility is likely clinically relevant, as fluconazole-resistant strains were subsequently recovered by the clinical laboratory during persistent or relapsing infections. In one patient, unrecognized respiration-deficient small colony variants are fluconazole-resistant and significantly attenuated for virulence during murine candidiasis. Our data suggest a population-based model of C. glabrata genotypic and phenotypic diversity during BSIs.
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Affiliation(s)
| | | | | | - Binghua Hao
- University of Pittsburgh, Pittsburgh, PA, USA
| | | | | | - Guojun Liu
- University of Pittsburgh, Pittsburgh, PA, USA
| | | | | | - Drishti Kaul
- J. Craig Venter Institute, La Jolla, CA, 92037, USA
| | | | - Cornelius J Clancy
- University of Pittsburgh, Pittsburgh, PA, USA
- VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
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14
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Farahani A, Ghiasvand F, Davoudi S, Ahmadinejad Z. Invasive aspergillosis in liver transplant recipients, an infectious complication with low incidence but significant mortality. World J Transplant 2023; 13:264-275. [PMID: 37746042 PMCID: PMC10514749 DOI: 10.5500/wjt.v13.i5.264] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 08/17/2023] [Accepted: 09/04/2023] [Indexed: 09/15/2023] Open
Abstract
BACKGROUND Infections, including invasive fungal infections (IFIs), are among the leading causes of mortality in liver transplant recipients during the first year post-transplantation. AIM To investigate the epidemiology, clinical manifestations, risk factors, treatment outcomes, and mortality rate of post-liver transplantation invasive aspergillosis (IA). METHODS In this case-control study, 22 patients with IA were identified by reviewing the archived and electronic medical records of 850 patients who received liver transplants at the Imam Khomeini Hospital complex in Tehran, Iran, between 2014 and 2019. The control group comprised 38 patients without IA infection matched for age and sex. The information obtained included the baseline characteristics of liver transplant patients, operative reports, post-transplantation characteristics of both groups and information about the fungal infection of the patient group. RESULTS The prevalence rate of IA among liver transplant recipients at Imam Khomeini Hospital was 2.7%. The risk factors of IA among studied patients included high serum creatinine levels before and post-transplant, renal replacement therapy, antithymocyte globulin induction therapy, post-transplant bile leakage, post-transplant hepatic artery thrombosis, repeated surgery within 30 d after the transplant, bacterial pneumonia before the aspergillosis diagnosis, receiving systemic antibiotics before the aspergillus infection, cytomegalovirus infection, and duration of post-transplant hospitalization in the intensive care unit. The most prevalent form of infection was invasive pulmonary aspergillosis, and the most common chest computed tomography scan findings were nodules, pleural effusion, and the halo sign. In the case group, prophylactic antifungal therapy was administered more frequently than in the control group. The antifungal therapy response rate at 12 wk was 63.7%. The 3- and 12- mo mortality rates of the patients with IA were 36.4% and 45.4%, respectively (compared with the mortality rate of the control group in 12 mo, which was zero). CONCLUSION In this study, the prevalence of IA among liver transplant recipients was relatively low. However, it was one of the leading causes of mortality following liver transplantation. Targeted antifungal therapy may be a factor in the low incidence of infections at our facility. Identifying the risk factors of IFIs, maintaining an elevated level of clinical suspicion, and initiating early antifungal treatment may significantly improve the prognosis and reduce the mortality rate of liver transplant recipients.
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Affiliation(s)
- Azam Farahani
- Department of Infectious Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran 1478714466, Iran
| | - Fereshteh Ghiasvand
- Department of Infectious Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran 1478714466, Iran
| | - Setareh Davoudi
- Department of Infectious Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran 1478714466, Iran
| | - Zahra Ahmadinejad
- Liver Transplantation Research Center, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran 1478714466, Iran
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15
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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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16
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Nanchal R, Subramanian R, Alhazzani W, Dionne JC, Peppard WJ, Singbartl K, Truwit J, Al-Khafaji AH, Killian AJ, Alquraini M, Alshammari K, Alshamsi F, Belley-Cote E, Cartin-Ceba R, Hollenberg SM, Galusca DM, Huang DT, Hyzy RC, Junek M, Kandiah P, Kumar G, Morgan RL, Morris PE, Olson JC, Sieracki R, Steadman R, Taylor B, Karvellas CJ. Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations. Crit Care Med 2023; 51:657-676. [PMID: 37052436 DOI: 10.1097/ccm.0000000000005824] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/14/2023]
Abstract
OBJECTIVES To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. DESIGN The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. INTERVENTIONS In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. CONCLUSIONS Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence.
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Affiliation(s)
- Rahul Nanchal
- Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI
| | | | - Waleed Alhazzani
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Joanna C Dionne
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | | | | | | | | | | | | | | | | | | | | | | | | | - David T Huang
- University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Mats Junek
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | | | - Gagan Kumar
- Northeast Georgia Medical Center, Gainesville, GA
| | - Rebecca L Morgan
- Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
| | - Peter E Morris
- University of Kentucky College of Medicine, Lexington, KY
| | - Jody C Olson
- Kansas University Medical Center, Kansas City, KS
| | | | - Randolph Steadman
- University of California Los Angeles Medical Center, Los Angeles, CA
| | | | - Constantine J Karvellas
- Department of Critical Care Medicine and Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
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17
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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: 12] [Impact Index Per Article: 6.0] [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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18
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Invasive Fungal Breakthrough Infections under Targeted Echinocandin Prophylaxis in High-Risk Liver Transplant Recipients. J Fungi (Basel) 2023; 9:jof9020272. [PMID: 36836384 PMCID: PMC9961099 DOI: 10.3390/jof9020272] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/15/2023] [Accepted: 02/17/2023] [Indexed: 02/22/2023] Open
Abstract
Invasive fungal infections (IFIs) are frequent and outcome-relevant complications in the early postoperative period after orthotopic liver transplantation (OLT). Recent guidelines recommend targeted antimycotic prophylaxis (TAP) for high-risk liver transplant recipients (HR-LTRs). However, the choice of antimycotic agent is still a subject of discussion. Echinocandins are increasingly being used due to their advantageous safety profile and the increasing number of non-albicans Candida infections. However, the evidence justifying their use remains rather sparse. Recently published data on breakthrough IFI (b-IFI) raise concerns about echinocandin efficacy, especially in the case of intra-abdominal candidiasis (IAC), which is the most common infection site after OLT. In this retrospective study, we analyzed 100 adult HR-LTRs undergoing first-time OLT and receiving echinocandin prophylaxis between 2017 and 2020 in a tertiary university hospital. We found a breakthrough incidence of 16%, having a significant impact on postoperative complications, graft survival, and mortality. The reasons for this may be multifactorial. Among the pathogen-related factors, we identified the breakthrough of Candida parapsilosis in 11% of patients and one case of persistent IFI due to the development of a secondary echinocandin resistance of an IAC caused by Candida glabrata. Consequently, the efficacy of echinocandin prophylaxis in liver transplantation should be questioned. Further studies are necessary to clarify the matter of breakthrough infections under echinocandin prophylaxis.
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19
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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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20
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Kriegl L, Boyer J, Egger M, Hoenigl M. Antifungal stewardship in solid organ transplantation. Transpl Infect Dis 2022; 24:e13855. [PMID: 35593394 PMCID: PMC9786549 DOI: 10.1111/tid.13855] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 05/10/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Antifungal stewardship (AFS) has emerged as an important component of quality in managing invasive fungal infections (IFIs), and cost-benefit calculations suggest regular training in AFS is well worth the effort. METHODS This review will discuss the most common IFIs in solid organ transplantation (SOT)-recipients, how to diagnose them, and current recommendations for antifungal treatment and prophylaxis before demonstrating key takeaway points of AFS in this high-risk population. RESULTS Effective AFS starts before a patient is admitted for SOT, through education and regular interactions of the interdisciplinary clinical team involved in patient management, considering local factors such as epidemiological data and knowledge of diagnostic options including local turnaround times. Understanding the spectrum of antifungal agents, their efficacy and safety profiles, and pharmacokinetics, as well as duration of therapy is hereby essential. The most frequent IFIs in SOT recipients are caused by Candida species, followed by Aspergillus species, both with increasing resistance rates. Diagnosis of IFI can be challenging due to unspecific clinical presentation and difficult interpretation of microbiological findings and biomarkers. Prophylactic strategies, such as those for invasive aspergillosis in lung transplantation or invasive candidiasis (IC) in certain liver transplant settings, as well as the selection of the appropriate therapeutic agents require detailed knowledge on the pharmacokinetics and drug-drug interactions of antifungals. CONCLUSIONS Here in this review, we address what constitutes good AFS in this heterogeneous field of solid organ transplant recipients.
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Affiliation(s)
- Lisa Kriegl
- Division of Infectious DiseasesDepartment of Internal MedicineMedical University of GrazGrazAustria
| | - Johannes Boyer
- Division of Infectious DiseasesDepartment of Internal MedicineMedical University of GrazGrazAustria
| | - Matthias Egger
- Division of Infectious DiseasesDepartment of Internal MedicineMedical University of GrazGrazAustria,BioTechMed‐GrazGrazAustria
| | - Martin Hoenigl
- Division of Infectious DiseasesDepartment of Internal MedicineMedical University of GrazGrazAustria,BioTechMed‐GrazGrazAustria,Division of Infectious Diseases and Global Public HealthDepartment of MedicineUniversity of California San DiegoSan DiegoCaliforniaUSA
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21
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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: 5] [Impact Index Per Article: 1.7] [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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22
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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: 18] [Impact Index Per Article: 6.0] [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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23
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Phoompoung P, Herrera S, Pérez Cortés Villalobos A, Foroutan F, Orchanian-Cheff A, Husain S. Risk factors of invasive fungal infections in liver transplant recipients: A systematic review and meta-analysis. Am J Transplant 2022; 22:1213-1229. [PMID: 34953174 DOI: 10.1111/ajt.16935] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 12/15/2021] [Accepted: 12/16/2021] [Indexed: 01/25/2023]
Abstract
Invasive fungal infections (IFIs) remain one of the most common infectious complications after organ transplantation, and liver transplant recipients (LTRs) have the highest mortality rate. However, risk factors associated with IFIs have only been evaluated in small single-center studies. We performed a meta-analysis by conducting a comprehensive search using Ovid MEDLINE, Ovid Embase, Cochrane database of systematic reviews, and Cochrane central register of controlled trials. All case-control and cohort studies evaluating risk factors for IFIs in adult LTRs were screened. Utilizing a random-effects model, a multivariate analysis was completed, and 28 studies were eligible for meta-analysis. Rates of IFIs ranged from 1.4% to 32.7%. Previous antibiotic use (OR 9.3; 95% CI 3.2-27.0) and bacterial infection (OR 4.3; 95% CI 2.1-8.6) were risk factors of invasive candidiasis. Yet for invasive aspergillosis, posttransplant renal replacement therapy (OR 9.2; 95% CI 4.2-20.4), reoperation (OR 8.0; 95% CI 2.9-21.7), and cytomegalovirus infection (OR 6.2; 95% CI 2.0-19.3) were risk factors. The top independent risk factors for IFIs during studies from 2010 to 2019 were previous fungal colonization (OR 9.19; 95% CI 4.92-17.16), reoperation (OR 5.45; 95% CI 2.93-10.15), and previous bacterial infections (OR 3.81; 95% CI 2.13-6.83). These risk factors may be targeted by antifungal prophylaxis in LTRs.
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Affiliation(s)
- Pakpoom Phoompoung
- Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada.,Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sabina Herrera
- Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada
| | | | - Farid Foroutan
- Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada
| | - Ani Orchanian-Cheff
- Library and Information Services, University Health Network, Toronto, Ontario, Canada
| | - Shahid Husain
- Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada
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24
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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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25
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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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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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Liu M, Zhu Z, Sun L. Risk Factors of Invasive Fungal Infection in Recipients After Liver Transplantation: A Systematic Review and Meta-Analysis. Front Med (Lausanne) 2021; 8:687028. [PMID: 34671611 PMCID: PMC8522940 DOI: 10.3389/fmed.2021.687028] [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: 03/30/2021] [Accepted: 08/31/2021] [Indexed: 12/30/2022] Open
Abstract
Objectives: Invasive fungal infection (IFI) remains an important cause of mortality in liver transplantation (LT). The objective of this meta-analysis was to identify the risk factors for IFI after LT. Methods: We searched for relevant studies published up to June 2020 from PubMed, Web of Science, Embase, and the Cochrane Library. Odds ratios (ORs) and their corresponding 95% CIs were used to identify significant differences in the risk factors. Heterogeneity between studies was evaluated by the I2 test, and potential publication bias was assessed with Egger's test. The quality of included studies was evaluated with the Newcastle-Ottawa Scale (NOS). Results: A total of 14 studies enrolling 4,284 recipients were included in the meta-analysis. Reoperation (OR = 2.18, 95% CI: 1.61–2.94), posttransplantation dialysis (OR = 2.03, 95% CI: 1.52–2.72), bacterial infection (OR = 1.81, 95% CI: 1.33–2.46), live donor (OR = 1.78, 95% CI: 1.20–2.63), retransplantation (OR = 2.45, 95% CI: 1.54–3.89), and fungal colonization (OR = 2.60, 95% CI: 1.99–3.42) were associated with the risk factors of IFI after LT. Conclusions: Despite some risk factors that have been identified as significant factors for IFI post-LT, which may inform prevention recommendations, rigorous and well-designed studies with adequate sample sizes should be conducted to solve the limitations of this study.
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Affiliation(s)
- Min Liu
- Department of Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,National Clinical Research Centre for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhijun Zhu
- Department of Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,National Clinical Research Centre for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Liying Sun
- Department of Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,National Clinical Research Centre for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.,Department of Intensive Care Unit, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Yetmar ZA, Lahr B, Brumble L, Gea Banacloche J, Steidley DE, Kushwaha S, Beam E. Epidemiology, risk factors, and association of antifungal prophylaxis on early invasive fungal infection in heart transplant recipients. Transpl Infect Dis 2021; 23:e13714. [PMID: 34435415 DOI: 10.1111/tid.13714] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 07/21/2021] [Accepted: 08/06/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND Invasive fungal infection (IFI) in heart transplant recipients is associated with poor outcomes. Estimated risk of 1-year IFI in heart transplant recipients is 3.4-8.6% with risk factors inconsistently identified in previous studies. The role of antifungal prophylaxis is unclear. The transplant program at Mayo Clinic provides 6 months of universal azole prophylaxis for those heart transplant recipients in Arizona. We sought to define risk factors for 1-year IFI and determine the effect of antifungal prophylaxis. METHODS We conducted a retrospective cohort study of patients undergoing heart transplantation at Mayo Clinic from January 2000 to March 2019. We analyzed demographics, details of transplant hospitalization, antifungal prophylaxis, and fungal infection. Multivariable Cox analyses were performed to identify risk factors of 1-year IFI and impact of IFI on posttransplant mortality. RESULTS A total of 966 heart transplant recipients were identified with a median age of 56 years (IQR 47, 62). A total of 444 patients received antifungal prophylaxis. Over 1-year follow-up, 62 patients developed IFI with a cumulative incidence of 6.4%. In multivariable analysis, factors associated with IFI were renal replacement therapy (RRT) (HR 3.24, 95% CI 1.65-6.39), allograft rejection (HR 2.33, 95% CI 1.25-4.34), and antifungal prophylaxis (HR 0.32, 95% CI 0.11-0.96). RRT was also associated with invasive mold infection (HR 3.00, 95% CI 1.29-6.97). CONCLUSIONS RRT and allograft rejection after transplantation are associated with 1-year IFI, and RRT is also associated with invasive mold infection. Antifungal prophylaxis appears to be protective and further study is needed in the heart transplant population.
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Affiliation(s)
- Zachary A Yetmar
- Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota
| | - Brian Lahr
- Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Lisa Brumble
- Division of Infectious Diseases, Mayo Clinic, Jacksonville, Florida
| | | | - D Eric Steidley
- Division of Cardiovascular Diseases, Mayo Clinic, Phoenix, Arizona
| | - Sudhir Kushwaha
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
| | - Elena Beam
- Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota
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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] [MESH Headings] [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 DiseasesIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Michele Bartoletti
- Division of Infectious DiseasesIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
- Department of Medical and Surgical SciencesAlma Mater Studiorum University of BolognaBolognaItaly
| | - Alberto Ferrarese
- Multivisceral Transplant Unit (Gastroenterology)Department of Surgery Oncology and GastroenterologySurgical and Gastroenterological SciencesPadua University HospitalPaduaItaly
| | - Erica Franceschini
- Infectious Diseases UnitDepartment of Nephrology Dialysis and Transplant UnitUniversity Hospital of ModenaModenaItaly
| | - Caterina Campoli
- Division of Infectious DiseasesIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Simona Coladonato
- Division of Infectious DiseasesIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Renato Pascale
- Division of Infectious DiseasesIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Sara Tedeschi
- Division of Infectious DiseasesIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
- Department of Medical and Surgical SciencesAlma Mater Studiorum University of BolognaBolognaItaly
| | - Milo Gatti
- Department of Medical and Surgical SciencesAlma Mater Studiorum University of BolognaBolognaItaly
| | - Monica Cricca
- Operative Unit of Clinical MicrobiologyPoliclinicoSant' Orsola MalpighiUniversity of BolognaBolognaItaly
| | - Simone Ambretti
- Infectious Diseases UnitDepartment of Nephrology Dialysis and Transplant UnitUniversity Hospital of ModenaModenaItaly
| | - Antonio Siniscalchi
- Division of AnesthesiaIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Maria Cristina Morelli
- Division of Internal Medicine for the Treatment of Severe Organ FailureIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Matteo Cescon
- Department of Medical and Surgical SciencesAlma Mater Studiorum University of BolognaBolognaItaly
- Division of Liver and Multiorgan TransplantIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Umberto Cillo
- Department of Surgical, Oncological, and Gastroenterological SciencesHepatobiliary Surgery and Liver Transplantation UnitPadua University HospitalPadovaItaly
| | - Fabrizio Di Benedetto
- Hepato‐Pancreato‐Biliary Surgery and Liver Transplantation UnitUniversity of Modena and Reggio EmiliaModenaItaly
| | - Patrizia Burra
- Multivisceral Transplant Unit (Gastroenterology)Department of Surgery Oncology and GastroenterologySurgical and Gastroenterological SciencesPadua University HospitalPaduaItaly
| | - Cristina Mussini
- Infectious Diseases UnitDepartment of Nephrology Dialysis and Transplant UnitUniversity Hospital of ModenaModenaItaly
| | | | - Russell Lewis
- Division of Infectious DiseasesIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
- Department of Medical and Surgical SciencesAlma Mater Studiorum University of BolognaBolognaItaly
| | - Pierluigi Viale
- Division of Infectious DiseasesIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
- Department of Medical and Surgical SciencesAlma Mater Studiorum University of BolognaBolognaItaly
| | - Maddalena Giannella
- Division of Infectious DiseasesIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
- Department of Medical and Surgical SciencesAlma Mater Studiorum University of BolognaBolognaItaly
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30
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Liver Transplantation in Patients With Pretransplant Aspergillus Colonization: Is It Safe to Proceed? Transplantation 2021; 105:586-592. [PMID: 32301905 DOI: 10.1097/tp.0000000000003276] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Patients with end-stage liver disease and pretransplant Aspergillus colonization are problematic for determining liver transplant candidacy and timing of transplantation because of concerns for posttransplant invasive aspergillosis. METHODS We performed a retrospective review of the medical and laboratory records of all adult patients (aged ≥18 y) who underwent liver transplantation with pretransplant Aspergillus colonization at the Ronald Reagan University of California, Los Angeles, Medical Center from January 1, 2010, to December 31, 2015. RESULTS A total of 27 patients who had Aspergillus colonization (respiratory tract 26, biliary tract 1) before liver transplantation were identified. Pretransplant characteristics included previous liver transplant (11 of 27, 40.7%), dialysis (22 of 27, 81.5%), corticosteroid therapy (12 of 27, 44.4%), intensive care unit stay (27 of 27, 100%), and median model for end-stage liver disease score of 39. Only 22.2% (6 of 27) received pretransplant antifungal agents (median duration, 5 d), whereas 100% (27 of 27) received posttransplant antifungal prophylaxis (voriconazole 81.4%, 22 of 27; echinocandin 14.8%, 4 of 27; voriconazole plus echinocandin 3.7%, 1 of 27) for median duration of 85 d. Posttransplant invasive fungal infection occurred in 14.8% (4 of 27; aspergillosis 3, mucormycosis 1). Both 6-month and 12-month survival were 66.7% (18 of 27), but only 1 death was due to fungal infection. Other causes of death were liver graft failure, intraabdominal complications, and malignancy. CONCLUSIONS A substantial number of patients with pretransplant Aspergillus colonization can still undergo successful liver transplantation if they are otherwise suitable candidates and receive appropriate antifungal prophylaxis. Posttransplant outcome in these patients is determined mostly by noninfectious complications and not fungal infection. Pretransplant Aspergillus colonization alone should not necessarily preclude or delay liver transplantation.
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31
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Preliver Transplant Aspergillus Colonization: An Ounce of Prevention. Transplantation 2021; 105:474-475. [PMID: 32301908 DOI: 10.1097/tp.0000000000003277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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32
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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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Talapko J, Juzbašić M, Matijević T, Pustijanac E, Bekić S, Kotris I, Škrlec I. Candida albicans-The Virulence Factors and Clinical Manifestations of Infection. J Fungi (Basel) 2021; 7:79. [PMID: 33499276 PMCID: PMC7912069 DOI: 10.3390/jof7020079] [Citation(s) in RCA: 326] [Impact Index Per Article: 81.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 01/17/2021] [Accepted: 01/21/2021] [Indexed: 02/06/2023] Open
Abstract
Candida albicans is a common commensal fungus that colonizes the oropharyngeal cavity, gastrointestinal and vaginal tract, and healthy individuals' skin. In 50% of the population, C. albicans is part of the normal flora of the microbiota. The various clinical manifestations of Candida species range from localized, superficial mucocutaneous disorders to invasive diseases that involve multiple organ systems and are life-threatening. From systemic and local to hereditary and environmental, diverse factors lead to disturbances in Candida's normal homeostasis, resulting in a transition from normal flora to pathogenic and opportunistic infections. The transition in the pathophysiology of the onset and progression of infection is also influenced by Candida's virulence traits that lead to the development of candidiasis. Oral candidiasis has a wide range of clinical manifestations, divided into primary and secondary candidiasis. The main supply of C. albicans in the body is located in the gastrointestinal tract, and the development of infections occurs due to dysbiosis of the residential microbiota, immune dysfunction, and damage to the muco-intestinal barrier. The presence of C. albicans in the blood is associated with candidemia-invasive Candida infections. The commensal relationship exists as long as there is a balance between the host immune system and the virulence factors of C. albicans. This paper presents the virulence traits of Candida albicans and clinical manifestations of specific candidiasis.
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Affiliation(s)
- Jasminka Talapko
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia; (J.T.); (M.J.)
| | - Martina Juzbašić
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia; (J.T.); (M.J.)
| | - Tatjana Matijević
- Department of Dermatology and Venereology, Clinical Hospital Center Osijek, HR-31000 Osijek, Croatia;
| | - Emina Pustijanac
- Faculty of Natural Sciences, Juraj Dobrila University of Pula, HR-52100 Pula, Croatia;
| | - Sanja Bekić
- Family Medicine Practice, HR-31000 Osijek, Croatia;
- Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia
| | - Ivan Kotris
- Department of Internal Medicine, General County Hospital Vukovar, HR-3200 Vukovar, Croatia;
| | - Ivana Škrlec
- Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, HR-31000 Osijek, Croatia; (J.T.); (M.J.)
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34
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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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35
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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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36
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Theodoropoulos NM, Bolstorff B, Bozorgzadeh A, Brandeburg C, Cumming M, Daly JS, Ellison RT, Forsberg K, Gade L, Gibson L, Greenough T, Litvintseva AP, Mack DA, Madoff L, Martins PN, McHale E, Melvin Z, Movahedi B, Stiles T, Vallabhaneni S, Levitz SM. Candida auris outbreak involving liver transplant recipients in a surgical intensive care unit. Am J Transplant 2020; 20:3673-3679. [PMID: 32530145 DOI: 10.1111/ajt.16144] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 06/05/2020] [Accepted: 06/06/2020] [Indexed: 01/25/2023]
Abstract
Candida auris is a yeast that is difficult to eradicate and has caused outbreaks in health care facilities. We report a cluster of 5 patients in 1 intensive care unit who were colonized or infected in 2017. The initial 2 patients were recipients of liver transplants who had cultures that grew C auris within 3 days of each other in June 2017 (days 43 and 30 posttransplant). Subsequent screening cultures identified 2 additional patients with C auris colonization. Respiratory and urine cultures from a fifth patient yielded C auris. All isolates were fluconazole resistant but susceptible to echinocandins. Whole genome sequencing showed the strains were clonal, suggesting in-hospital transmission, and related but distinct from New York/New Jersey strains, consistent with a separate introduction. However, no source or contact was found. Two of the 5 patients died. C auris infection likely contributed to 1 patient death by infecting a vascular aneurysm at the graft anastomosis. Strict infection control precautions were initiated to control the outbreak. Our experience reveals that although severe disease from C auris can occur in transplant recipients, outbreaks can be controlled using recommended infection control practices. We have had no further patients infected with C auris to date.
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Affiliation(s)
- Nicole M Theodoropoulos
- Division of Infectious Disease, University of Massachusetts Medical School, Worcester, Massachusetts
| | | | - Adel Bozorgzadeh
- Division of Transplant Surgery, University of Massachusetts Medical School, Worcester, Massachusetts
| | | | - Melissa Cumming
- Massachusetts Department of Public Health, Boston, Massachusetts
| | - Jennifer S Daly
- Division of Infectious Disease, University of Massachusetts Medical School, Worcester, Massachusetts
| | - Richard T Ellison
- Division of Infectious Disease, University of Massachusetts Medical School, Worcester, Massachusetts
| | | | - Lalitha Gade
- Centers for Disease Control & Prevention, Atlanta, Georgia
| | - Laura Gibson
- Division of Infectious Disease, University of Massachusetts Medical School, Worcester, Massachusetts
| | - Thomas Greenough
- Division of Infectious Disease, University of Massachusetts Medical School, Worcester, Massachusetts
| | | | - Deborah A Mack
- UMass Memorial Medical Center Infection Control Department, Worcester, Massachusetts
| | - Lawrence Madoff
- Massachusetts Department of Public Health, Boston, Massachusetts
| | - Paulo N Martins
- Division of Transplant Surgery, University of Massachusetts Medical School, Worcester, Massachusetts
| | - Eileen McHale
- Massachusetts Department of Public Health, Boston, Massachusetts
| | - Zita Melvin
- UMass Memorial Medical Center Infection Control Department, Worcester, Massachusetts
| | - Babak Movahedi
- Division of Transplant Surgery, University of Massachusetts Medical School, Worcester, Massachusetts
| | - Tracy Stiles
- Massachusetts Department of Public Health, Boston, Massachusetts
| | | | - Stuart M Levitz
- Division of Infectious Disease, University of Massachusetts Medical School, Worcester, Massachusetts
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37
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Decker SO, Incamps A, Wilk H, Uhle F, Bruckner T, Heininger A, Zimmermann S, Mehrabi A, Mieth M, Weiss KH, Weigand MA, Brenner T. Soluble intercellular adhesion molecule (ICAM)-1 detects invasive fungal infections in patients following liver transplantation. Biomarkers 2020; 25:548-555. [PMID: 32803993 DOI: 10.1080/1354750x.2020.1810318] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
PURPOSE Despite antifungal prophylaxis, liver transplanted patients are endangered by invasive fungal infections (IFI). Routinely used microbiological procedures are hallmarked by significant weaknesses, which may lead to a delay in antifungal treatment. METHODS Culture-based fungal findings, routinely used biomarkers of infection/inflammation (e.g., procalcitonin or C-reactive protein), as well as corresponding plasma concentrations of soluble Intercellular Adhesion Molecule (ICAM)-1 were analysed in 93 patients during a period of 28 days following liver transplantation (LTX). RESULTS Plasmatic sICAM-1 was significantly elevated in patients affected by an IFI within the first 28 days in comparison to fungally colonised or unobtrusive LTX patients. sICAM-1 might therefore be helpful for the identification of IFI patients after LTX (e.g., Receiver Operating Characteristic (ROC)-Area Under the Curve (AUC): 0.714 at 14d after LTX). The diagnostic performance of sICAM-1 was further improved by its combined use with different other IFI biomarkers (e.g., midregional proadrenomedullin). CONCLUSION The diagnostic deficiencies of routinely used microbiological procedures for IFI detection in patients after LTX may be reduced by plasmatic sICAM-1 measurements. Clinical Trial Notation. German Clinical Trials Register: DRKS00005480.
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Affiliation(s)
- Sebastian O Decker
- Department of Anesthesiology, Heidelberg University Hospital, , Heidelberg, Germany
| | - Anne Incamps
- Thermo Fisher Scientific Cezanne SAS, Clinical Diagnostic Division, Nimes, France
| | - Henryk Wilk
- Department of Anesthesiology, Heidelberg University Hospital, , Heidelberg, Germany
| | - Florian Uhle
- Department of Anesthesiology, Heidelberg University Hospital, , Heidelberg, Germany
| | - Thomas Bruckner
- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
| | - Alexandra Heininger
- Hospital Hygiene Staff Unit, University Medical Center Mannheim, Mannheim, Germany.,Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Heidelberg, Germany
| | - Stefan Zimmermann
- Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplant Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Karl Heinz Weiss
- Department of Internal Medicine IV, Heidelberg University Hospital, Heidelberg, Germany.,Salem Medical Centre, Heidelberg, Germany
| | - Markus A Weigand
- Department of Anesthesiology, Heidelberg University Hospital, , Heidelberg, Germany
| | - Thorsten Brenner
- Department of Anesthesiology, Heidelberg University Hospital, , Heidelberg, Germany.,Department of Anesthesiology and Intensive Care Medicine, Essen University Hospital, Essen, Germany
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38
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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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39
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Lavezzo B, Romagnoli R, Balagna R, De Rosa FG. The issue of the antifungal drug choice in prophylaxis of invasive fungal infection after liver transplant. Transpl Infect Dis 2019; 22:e13220. [PMID: 31782237 DOI: 10.1111/tid.13220] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 11/24/2019] [Indexed: 11/30/2022]
Affiliation(s)
- Bruna Lavezzo
- Anesthesia and Intensive Care Unit 2, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - Renato Romagnoli
- Liver Transplant Center, General Surgery 2, University of Torino, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - Roberto Balagna
- Anesthesia and Intensive Care Unit 2, A.O.U. Città della Salute e della Scienza, Torino, Italy
| | - Francesco 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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40
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Neyra KM, Brizendine KD. Retrospective study evaluating the performance of risk factors for invasive mold infections in liver transplantation. Transpl Infect Dis 2019; 22:e13223. [PMID: 31782873 DOI: 10.1111/tid.13223] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 10/03/2019] [Accepted: 11/24/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND Mold infections in liver transplant are associated with high mortality. Guidelines recommend prophylaxis targeted against mold based upon risk factors of fulminant hepatic failure, retransplantation, reoperation, and renal replacement therapy post-transplant. It is not known if these factors identify risk of mold infection at every center. METHODS A retrospective study was conducted of adult liver transplant recipients at a single center from 2010 to 2014. The association between risk factors and invasive mold infection and effect of antifungal prophylaxis were determined. RESULTS Five hundred thirty-four liver transplant recipients were identified. The overall incidence of invasive mold infection was 0.9% (N = 5). The incidence in patients with (N = 128) and without (N = 406) risk factors was 0.78% and 0.98%, respectively. Antifungal prophylaxis with mold activity was administered to 23/128 (18%) with risk factors, and none developed infection. No mold-active prophylaxis was given to 105/128 (82%) with risk factors, and incidence of mold infection was 0.95% (N = 1). Number needed to treat was 105. CONCLUSIONS Traditional risk factors for mold infection in liver transplant performed poorly. These results underscore the importance of transplant center-specific data to inform adoption of an antifungal prophylactic strategy. Studies are needed to determine alternative risk factors to facilitate appropriate targeting of antifungals.
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Affiliation(s)
- Karyna M Neyra
- Department of Infectious Disease, Cleveland Clinic, Cleveland, Ohio
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41
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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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42
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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: 87] [Impact Index Per Article: 14.5] [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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43
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Abbo LM, Grossi PA. Surgical site infections: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33:e13589. [PMID: 31077619 DOI: 10.1111/ctr.13589] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Accepted: 05/06/2019] [Indexed: 02/06/2023]
Abstract
These guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of post-operative surgical site infections (SSIs) in solid organ transplantation. SSIs are a significant cause of morbidity and mortality in SOT recipients. Depending on the organ transplanted, SSIs occur in 3%-53% of patients, with the highest rates observed in small bowel/multivisceral, liver, and pancreas transplant recipients. These infections are classified by increasing invasiveness as superficial incisional, deep incisional, or organ/space SSIs. The spectrum of organisms implicated in SSIs in SOT recipients is more diverse than the general population due to other important factors such as the underlying end-stage organ failure, immunosuppression, prolonged hospitalizations, organ transportation/preservation, and previous exposures to antibiotics in donors and recipients that could predispose to infections with multidrug-resistant organisms. In this guideline, we describe the epidemiology, clinical presentation, differential diagnosis, potential pathogens, and management. We also provide recommendations for the selection, dosing, and duration of peri-operative antibiotic prophylaxis to minimize post-operative SSIs.
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Affiliation(s)
- Lilian M Abbo
- Division of Infectious Diseases, Department of Medicine, University of Miami Miller School of Medicine and Jackson Health System, Miami, Florida
| | - Paolo Antonio Grossi
- Infectious Diseases Section, Department of Medicine and Surgery, University of Insubria, Varese, Italy
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44
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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: 168] [Impact Index Per Article: 28.0] [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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45
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Decker SO, Krüger A, Wilk H, Grumaz S, Vainshtein Y, Schmitt FCF, Uhle F, Bruckner T, Zimmermann S, Mehrabi A, Mieth M, Weiss KH, Weigand MA, Hofer S, Sohn K, Brenner T. New approaches for the detection of invasive fungal diseases in patients following liver transplantation-results of an observational clinical pilot study. Langenbecks Arch Surg 2019; 404:309-325. [PMID: 30834971 DOI: 10.1007/s00423-019-01769-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 02/21/2019] [Indexed: 12/13/2022]
Abstract
PURPOSE Despite antifungal prophylaxis following liver transplantation (LTX), patients are at risk for the development of subsequent opportunistic infections, such as an invasive fungal disease (IFD). However, culture-based diagnostic procedures are associated with relevant weaknesses. METHODS Culture and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of ß-D-glucan (BDG), galactomannan (GM), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A and mid-regional proadrenomedullin (MR-proADM) were evaluated in 93 patients at 6 consecutive time points within 28 days following LTX. RESULTS A NGS-based diagnostic approach was shown to be suitable for the early identification of fungal pathogens in patients following LTX. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with an IFD. CONCLUSION Plasma measurements of MR-proADM and IL-17A as well as a NGS-based diagnostic approach were shown to be attractive methodologies to attenuate the weaknesses of routinely used culture-based diagnostic procedures for the determination of an IFD in patients following LTX. However, an additional confirmation within a larger multicenter trial needs to be recommended. TRIAL REGISTRATION German Clinical Trials Register: DRKS00005480 .
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Affiliation(s)
- Sebastian O Decker
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Albert Krüger
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Henryk Wilk
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Silke Grumaz
- Fraunhofer IGB, Nobelstraße 12, 70569, Stuttgart, Germany
| | | | - Felix C F Schmitt
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Florian Uhle
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Thomas Bruckner
- Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 130, 69120, Heidelberg, Germany
| | - Stefan Zimmermann
- Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, Im Neuenheimer Feld 324, 69120, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplant Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Karl Heinz Weiss
- Department of Internal Medicine IV, Heidelberg University Hospital, Im Neunheimer Feld 410, 69120, Heidelberg, Germany
| | - Markus A Weigand
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany
| | - Stefan Hofer
- Department of Anesthesiology, Westpfalzklinikum, Hellmut-Hartert-Straße 1, 67655, Kaiserslautern, Germany
| | - Kai Sohn
- Fraunhofer IGB, Nobelstraße 12, 70569, Stuttgart, Germany
| | - Thorsten Brenner
- Department of Anesthesiology, Heidelberg University Hospital, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
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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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47
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Chiu YC, Ho MH, Chen TW, Hsieh CB, Fan HL. Twice-Weekly Tacrolimus Can Overcome Pharmacologic Interaction and Help in the Successful Treatment of Pulmonary Aspergillosis in a Liver Transplant Recipient. EXP CLIN TRANSPLANT 2018; 17:838-840. [PMID: 30373507 DOI: 10.6002/ect.2017.0171] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Drug-drug interactions between azoles and calcineurin inhibitors can cause issues for organ transplant specialists. Clinical practice guidelines for the treatment of solid-organ transplant recipients with invasive aspergillosis infection are lacking. Here, we present a patient who developed pulmonary aspergillosis after liver transplant. The patient had prolonged treatment with echinocandin that was not effective. A drug-drug interaction between azoles and tacrolimus caused issues for the clinical physician. We adjusted the doses, and the patient was successfully treated. A reduction in the tacrolimus dose, intensive monitoring of associated parameters, and elimination of risk exposures are important for a favorable outcome.
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Affiliation(s)
- Yu-Cheng Chiu
- From the Division of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
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48
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Brumble L, Keaveny AP. Editorial: The Risky Business of Fungal Infections in Patients with Cirrhosis. Am J Gastroenterol 2018; 113:564-566. [PMID: 29610500 DOI: 10.1038/ajg.2018.20] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2018] [Accepted: 01/05/2018] [Indexed: 12/11/2022]
Abstract
Hospitalized patients with cirrhosis have a high rate of mortality. In the report by Bajaj et al., the negative impact of fungal infections (FI) on outcomes in a large US cohort of hospitalized cirrhotics is highlighted. Risk factors for FI are identified. Increasing awareness of FI along with the application of new diagnostic tools in species identification will provide the opportunity to improve patient outcomes.
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Affiliation(s)
- Lisa Brumble
- Department of Medicine, Division of Infectious Disease, Mayo Clinic, Jacksonville, Florida, USA
| | - Andrew P Keaveny
- Department of Transplant, Mayo Clinic, Jacksonville, Florida, USA
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49
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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: 16] [Impact Index Per Article: 2.3] [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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Perioperative Antibiotic Prophylaxis to Prevent Surgical Site Infections in Solid Organ Transplantation. Transplantation 2018; 102:21-34. [DOI: 10.1097/tp.0000000000001848] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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