Matteo Bassetti1,2, Jose Garnacho-Montero3, Thierry Calandra4, Bartjan Kullberg5, George Dimopoulos6, Elie Azoulay7, Arunaloke Chakrabarti8, Daniel Kett9, Cristobal Leon10, Luis Ostrosky-Zeichner11, Maurizio Sanguinetti12, Jean-Francois Timsit13, Malcom D Richardson14, Andrew Shorr15, Oliver A Cornely16. 1. Infectious Diseases Clinic, Santa Maria Misericordia Hospital, University of Udine, Udine, Italy. mattba@tin.it. 2. Clinica Malattie Infettive, Azienda Sanitaria Universitaria Integrata, Presidio Ospedaliero Santa Maria della Misericordia, Piazzale S. Maria della Misericordia, n. 15, 33100, Udine, Italy. mattba@tin.it. 3. Unidad Clínica de Cuidados Intensivos, Hospital Universitario Virgen Macarena and Institute of Biomedicine of Seville, IBiS/CSIC/University of Seville, seville, Spain. 4. Infectious Diseases Service, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland. 5. Department of Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands. 6. Department of Critical Care, University Hospital ATTIKON, National and Kapodistrian University of Athens, Athens, Greece. 7. Medical Intensive Care Unit, Hôpital Saint-Louis, ECSTRA Team, Biostatistics and Clinical Epidemiology, Paris Diderot Sorbonne University, Paris, France. 8. Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 9. Division of Pulmonary and Critical Care Medicine, The Leonard M. Miller School of Medicine at the University of Miami, Miami, FL, USA. 10. Intensive Care Unit, Hospital Universitario de Valme, Universidad de Sevilla, Seville, Spain. 11. Division of Infectious Diseases, McGovern Medical School, UTHealth, Houston, USA. 12. Institute of Microbiology, Università Cattolica del Sacro Cuore, Rome, Italy. 13. 1UMR1137-IAMETeam 5, Decision Sciences in Infectious Disease Prevention, Control and Care, Paris Diderot University-Inserm, Sorbonne Paris Cité and 2AP-HP, Medical and Infectious Diseases ICU, Bichat Hospital, Paris, France. 14. Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK. 15. Pulmonary and Critical Care Medicine, Medstar Washington Hospital Center, Washington, USA. 16. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Clinical Trials Centre Cologne (ZKS Köln), Department I of Internal Medicine, German Centre for Infection Research (DZIF), University of Cologne, Cologne, Germany.
Abstract
PURPOSE: To describe concisely the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to Candida and Aspergillus infections in non-neutropenic patients in the ICU setting. METHODS: A systematic review of the medical literature taking account of national and international guidelines and expert opinion. RESULTS: Severe invasive fungal infections (IFIs) are becoming increasingly frequent in critically ill patients. Approximately 80% of IFIs are due to Candida spp. and 0.3-19% to Aspergillus spp. Recent observations emphasize the necessity of building a worldwide sentinel network to monitor the emergence of new fungal species and changes in susceptibility. Robust data on the attributable mortality are essential for the design of clinical studies with mortality endpoints. Although early antifungal therapy for Candida has been recommended in patients with risk factors, sepsis of unknown cause, and positive Candida serum biomarkers [β-1 → 3-D-glucan (BDG) and Candida albicans germ tube antibody (CAGTA)], its usefulness and influence on outcome need to be confirmed. Future studies may specifically address the optimal diagnostic and therapeutic strategies for patients with abdominal candidiasis. Better knowledge of the pharmacokinetics of antifungal molecules and tissue penetration is a key issue for intensivists. Regarding invasive aspergillosis, further investigation is needed to determine its incidence in the ICU, its relationship with influenza outbreaks, the clinical impact of rapid diagnosis, and the significance of combination treatment. CONCLUSIONS: Fundamental questions regarding IFI have to be addressed over the next decade. The clinical studies described in this research agenda should provide a template and set priorities for the clinical investigations that need to be performed.
PURPOSE: To describe concisely the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to Candida and Aspergillus infections in non-neutropenicpatients in the ICU setting. METHODS: A systematic review of the medical literature taking account of national and international guidelines and expert opinion. RESULTS: Severe invasive fungal infections (IFIs) are becoming increasingly frequent in critically illpatients. Approximately 80% of IFIs are due to Candida spp. and 0.3-19% to Aspergillus spp. Recent observations emphasize the necessity of building a worldwide sentinel network to monitor the emergence of new fungal species and changes in susceptibility. Robust data on the attributable mortality are essential for the design of clinical studies with mortality endpoints. Although early antifungal therapy for Candida has been recommended in patients with risk factors, sepsis of unknown cause, and positive Candida serum biomarkers [β-1 → 3-D-glucan (BDG) and Candida albicans germ tube antibody (CAGTA)], its usefulness and influence on outcome need to be confirmed. Future studies may specifically address the optimal diagnostic and therapeutic strategies for patients with abdominal candidiasis. Better knowledge of the pharmacokinetics of antifungal molecules and tissue penetration is a key issue for intensivists. Regarding invasive aspergillosis, further investigation is needed to determine its incidence in the ICU, its relationship with influenza outbreaks, the clinical impact of rapid diagnosis, and the significance of combination treatment. CONCLUSIONS: Fundamental questions regarding IFI have to be addressed over the next decade. The clinical studies described in this research agenda should provide a template and set priorities for the clinical investigations that need to be performed.
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