J Antimicrob Chemother 2013; 68 Suppl 3: iii3 – iii4 doi:10.1093/jac/dkt393
Introduction and aims J. Peter Donnelly* Department of Haematology and Nijmegen Institute for Infection, Inflammation and Immunity, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands *Corresponding author. Tel: +31-24-361-9987; Fax: +31-24-361-2080; E-mail: [email protected]
Keywords: invasive fungal disease, prophylaxis, diagnostic-driven treatment, triggers, multidisciplinary team management
strategies and an integrated multidisciplinary management plan for patients at risk of IFD. The experts were divided into three groups, each guided by a Chairperson, to focus on driving change within their country in one of the following topics: (i) personalized risk assessment and the indications for prophylaxis (who are the right patients and how can treatment be optimized in this group?); (ii) triggers for treatment (how can integrated care pathways be more effectively utilized?); and (iii) integrated multidisciplinary management (what protocol or key requirements can be proposed as a process to guide clinical practice?). To facilitate this process, the Chairpersons summarized the evidence base, identified gaps in knowledge and outlined key discussion points. They then facilitated group discussions, which were led by a designated group leader. Each group was asked to consider how they would propose a change in the way care is provided, recommend actions and identify practical considerations based on the centre and the country they represent, to help provide an international perspective. The participants reconvened in a plenary session, during which the main points on each topic were presented to the whole group for further discussion and refinement. Participants then worked independently to develop the three articles published in this Supplement. I would like to thank the authors for their lively contributions and thoughtful discussions and hope that their efforts will stimulate the clinical community to provide the best care for patients with IFD, wherever they practice.
Acknowledgements HealthCare21 organized the meeting, provided logistical support to the speakers and provided editorial support in preparing the final manuscripts. The authors are also indebted to Pfizer Ilaclari Ltd Sti. for providing an unrestricted educational grant to facilitate the entire undertaking.
Funding Pfizer Ilaclari Ltd Sti. provided an unrestricted educational grant to facilitate the entire undertaking.
# The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected]
iii3
Downloaded from http://jac.oxfordjournals.org/ at Universite Laval on June 21, 2014
Invasive fungal disease (IFD) is associated with significant morbidity, mortality and costs.1 The incidence of IFD, especially invasive pulmonary aspergillosis, continues to increase in parallel with the increasing number of patients undergoing intensive chemotherapy to treat haematological malignancies or receiving a haematological stem cell transplant (HSCT).2,3 Existing data suggest an incidence of IFD of 7– 8 cases per 100 allogeneic HSCTs in North America and there is no reason to suppose the rate will be any different in Europe.4 The diagnosis of fungal infection is complex and delays in starting antifungal therapy are associated with increased mortality.5 This has led to three broad approaches to management: (i) prophylaxis when the patient is at risk of IFD on admission for chemotherapy or conditioning therapy for an HSCT;6 (ii) empirical antifungal therapy when the patient is ill and IFD is either suspected or cannot be excluded; and, more recently, (iii) detection of signs of invasive fungal infection or disease early enough to start targeted therapy.6 – 9 Prophylaxis is recommended for certain groups that are considered to be at high risk, but opinions are divided on the costeffectiveness of the approach.6,10,11 Empirical antifungal therapy has long been adopted as a standard of care, but concerns about overtreatment and the associated toxicities and costs have led to a desire to seek an alternative approach.12 This has been variously called ‘pre-emptive’ or ‘diagnostic driven’ to emphasize the need for tests, be they radiographic or mycological.12 The definitions of IFD by The European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/ MSG) rely on clinical and mycological diagnostic criteria to assign certainty of diagnosis to three groups, namely ‘proven’, ‘probable’ and ‘possible’.13 However, the definitions were not meant to be used to guide clinical practice as only a minority of cases meet the criteria at the point where clinicians want to decide to treat or not. This led Maertens et al. 14 to propose a spectrum of conditions in which there was either clinical or mycological evidence to support a potential diagnosis of IFD that could trigger action, be it further diagnosis or treatment or both. To further explore this, a meeting was convened of 16 experts representing key clinical centres, principally from across Europe but including Israel and India. Their task was to develop an ‘international process’ for implementing diagnostic and treatment
Donnelly
Transparency declarations This article is part of a Supplement sponsored by Pfizer Ilaclari Ltd Sti. J.P.D. has received research grants and speaker’s fees from Astellas, Gilead Sciences Inc. Merck, Sharp and Dohme and Pfizer Inc., and is a consultant and scientific advisor for Astellas, Gilead Sciences Inc. and Pfizer Inc. The authors received modest financial compensation for their time and expenses in attending a meeting in Vienna to discuss the contents of the articles.
References 1 Menzin J, Meyers JL, Friedman M et al. Mortality, length of hospitalization, and costs associated with invasive fungal infections in high-risk patients. Am J Health-System Pharmacy 2009; 66: 1711–7.
3 Pagano L, Caira M, Nosari A et al. Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study—Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne. Clin Infect Dis 2007; 45: 1161 –70. 4 Kontoyiannis DP, Marr KA, Park BJ et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 2010; 50: 1091–100. 5 Maertens J, Groll AH, Cordonnier C et al. Treatment and timing in invasive mould disease. J Antimicrob Chemother 2011; 66 Suppl 1: i37– 43. 6 Rogers TR, Slavin MA, Donnelly JP. Antifungal prophylaxis during treatment for haematological malignancies: are we there yet? Brit J Haematol 2011; 153: 681–97.
iii4
8 Maertens J, Marchetti O, Herbrecht R et al. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3—2009 update. Bone Marrow Transplant 2011; 46: 709–18. 9 Ruping MJ, Vehreschild JJ, Groll A et al. Current issues in the clinical management of invasive aspergillosis—the AGIHO, DMykG, OGMM and PEG web-based survey and expert consensus conference 2009. Mycoses 2011; 54: e557– 68. 10 Ananda-Rajah MR, Cheng A, Morrissey CO et al. Attributable hospital cost and antifungal treatment of invasive fungal diseases in high-risk hematology patients: an economic modeling approach. Antimicrob Agents Chemother 2011; 55: 1953– 60. 11 Xu SX, Shen JL, Tang XF et al. Newer antifungal agents for fungal infection prevention during hematopoietic cell transplantation: a metaanalysis. Transplant Proc 2013; 45: 407–14. 12 Agrawal S, Hope W, Sinko J et al. Optimizing management of invasive mould diseases. J Antimicrob Chemother 2011; 66 Suppl 1: i45–53. 13 De Pauw B, Walsh TJ, Donnelly JP et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813– 21. 14 Maertens JA, Nucci M, Donnelly JP. The role of antifungal treatment in hematology. Haematologica 2012; 97: 325– 7.
Downloaded from http://jac.oxfordjournals.org/ at Universite Laval on June 21, 2014
2 Maschmeyer G, Haas A, Cornely OA. Invasive aspergillosis: epidemiology, diagnosis and management in immunocompromised patients. Drugs 2007; 67: 1567– 601.
7 Freifeld AG, Bow EJ, Sepkowitz KA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2011; 52: e56–93.
Introduction and aims J. Peter Donnelly* Department of Haematology and Nijmegen Institute for Infection, Inflammation and Immunity, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands *Corresponding author. Tel: +31-24-361-9987; Fax: +31-24-361-2080; E-mail: [email protected]
Keywords: invasive fungal disease, prophylaxis, diagnostic-driven treatment, triggers, multidisciplinary team management
strategies and an integrated multidisciplinary management plan for patients at risk of IFD. The experts were divided into three groups, each guided by a Chairperson, to focus on driving change within their country in one of the following topics: (i) personalized risk assessment and the indications for prophylaxis (who are the right patients and how can treatment be optimized in this group?); (ii) triggers for treatment (how can integrated care pathways be more effectively utilized?); and (iii) integrated multidisciplinary management (what protocol or key requirements can be proposed as a process to guide clinical practice?). To facilitate this process, the Chairpersons summarized the evidence base, identified gaps in knowledge and outlined key discussion points. They then facilitated group discussions, which were led by a designated group leader. Each group was asked to consider how they would propose a change in the way care is provided, recommend actions and identify practical considerations based on the centre and the country they represent, to help provide an international perspective. The participants reconvened in a plenary session, during which the main points on each topic were presented to the whole group for further discussion and refinement. Participants then worked independently to develop the three articles published in this Supplement. I would like to thank the authors for their lively contributions and thoughtful discussions and hope that their efforts will stimulate the clinical community to provide the best care for patients with IFD, wherever they practice.
Acknowledgements HealthCare21 organized the meeting, provided logistical support to the speakers and provided editorial support in preparing the final manuscripts. The authors are also indebted to Pfizer Ilaclari Ltd Sti. for providing an unrestricted educational grant to facilitate the entire undertaking.
Funding Pfizer Ilaclari Ltd Sti. provided an unrestricted educational grant to facilitate the entire undertaking.
# The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected]
iii3
Downloaded from http://jac.oxfordjournals.org/ at Universite Laval on June 21, 2014
Invasive fungal disease (IFD) is associated with significant morbidity, mortality and costs.1 The incidence of IFD, especially invasive pulmonary aspergillosis, continues to increase in parallel with the increasing number of patients undergoing intensive chemotherapy to treat haematological malignancies or receiving a haematological stem cell transplant (HSCT).2,3 Existing data suggest an incidence of IFD of 7– 8 cases per 100 allogeneic HSCTs in North America and there is no reason to suppose the rate will be any different in Europe.4 The diagnosis of fungal infection is complex and delays in starting antifungal therapy are associated with increased mortality.5 This has led to three broad approaches to management: (i) prophylaxis when the patient is at risk of IFD on admission for chemotherapy or conditioning therapy for an HSCT;6 (ii) empirical antifungal therapy when the patient is ill and IFD is either suspected or cannot be excluded; and, more recently, (iii) detection of signs of invasive fungal infection or disease early enough to start targeted therapy.6 – 9 Prophylaxis is recommended for certain groups that are considered to be at high risk, but opinions are divided on the costeffectiveness of the approach.6,10,11 Empirical antifungal therapy has long been adopted as a standard of care, but concerns about overtreatment and the associated toxicities and costs have led to a desire to seek an alternative approach.12 This has been variously called ‘pre-emptive’ or ‘diagnostic driven’ to emphasize the need for tests, be they radiographic or mycological.12 The definitions of IFD by The European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/ MSG) rely on clinical and mycological diagnostic criteria to assign certainty of diagnosis to three groups, namely ‘proven’, ‘probable’ and ‘possible’.13 However, the definitions were not meant to be used to guide clinical practice as only a minority of cases meet the criteria at the point where clinicians want to decide to treat or not. This led Maertens et al. 14 to propose a spectrum of conditions in which there was either clinical or mycological evidence to support a potential diagnosis of IFD that could trigger action, be it further diagnosis or treatment or both. To further explore this, a meeting was convened of 16 experts representing key clinical centres, principally from across Europe but including Israel and India. Their task was to develop an ‘international process’ for implementing diagnostic and treatment
Donnelly
Transparency declarations This article is part of a Supplement sponsored by Pfizer Ilaclari Ltd Sti. J.P.D. has received research grants and speaker’s fees from Astellas, Gilead Sciences Inc. Merck, Sharp and Dohme and Pfizer Inc., and is a consultant and scientific advisor for Astellas, Gilead Sciences Inc. and Pfizer Inc. The authors received modest financial compensation for their time and expenses in attending a meeting in Vienna to discuss the contents of the articles.
References 1 Menzin J, Meyers JL, Friedman M et al. Mortality, length of hospitalization, and costs associated with invasive fungal infections in high-risk patients. Am J Health-System Pharmacy 2009; 66: 1711–7.
3 Pagano L, Caira M, Nosari A et al. Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study—Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne. Clin Infect Dis 2007; 45: 1161 –70. 4 Kontoyiannis DP, Marr KA, Park BJ et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 2010; 50: 1091–100. 5 Maertens J, Groll AH, Cordonnier C et al. Treatment and timing in invasive mould disease. J Antimicrob Chemother 2011; 66 Suppl 1: i37– 43. 6 Rogers TR, Slavin MA, Donnelly JP. Antifungal prophylaxis during treatment for haematological malignancies: are we there yet? Brit J Haematol 2011; 153: 681–97.
iii4
8 Maertens J, Marchetti O, Herbrecht R et al. European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3—2009 update. Bone Marrow Transplant 2011; 46: 709–18. 9 Ruping MJ, Vehreschild JJ, Groll A et al. Current issues in the clinical management of invasive aspergillosis—the AGIHO, DMykG, OGMM and PEG web-based survey and expert consensus conference 2009. Mycoses 2011; 54: e557– 68. 10 Ananda-Rajah MR, Cheng A, Morrissey CO et al. Attributable hospital cost and antifungal treatment of invasive fungal diseases in high-risk hematology patients: an economic modeling approach. Antimicrob Agents Chemother 2011; 55: 1953– 60. 11 Xu SX, Shen JL, Tang XF et al. Newer antifungal agents for fungal infection prevention during hematopoietic cell transplantation: a metaanalysis. Transplant Proc 2013; 45: 407–14. 12 Agrawal S, Hope W, Sinko J et al. Optimizing management of invasive mould diseases. J Antimicrob Chemother 2011; 66 Suppl 1: i45–53. 13 De Pauw B, Walsh TJ, Donnelly JP et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813– 21. 14 Maertens JA, Nucci M, Donnelly JP. The role of antifungal treatment in hematology. Haematologica 2012; 97: 325– 7.
Downloaded from http://jac.oxfordjournals.org/ at Universite Laval on June 21, 2014
2 Maschmeyer G, Haas A, Cornely OA. Invasive aspergillosis: epidemiology, diagnosis and management in immunocompromised patients. Drugs 2007; 67: 1567– 601.
7 Freifeld AG, Bow EJ, Sepkowitz KA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2011; 52: e56–93.
