Intensive Care Medicine

, Volume 43, Issue 9, pp 1225–1238 | Cite as

Intensive care medicine research agenda on invasive fungal infection in critically ill patients

  • Matteo Bassetti
  • Jose Garnacho-Montero
  • Thierry Calandra
  • Bartjan Kullberg
  • George Dimopoulos
  • Elie Azoulay
  • Arunaloke Chakrabarti
  • Daniel Kett
  • Cristobal Leon
  • Luis Ostrosky-Zeichner
  • Maurizio Sanguinetti
  • Jean-Francois Timsit
  • Malcom D. Richardson
  • Andrew Shorr
  • Oliver A. Cornely
Research Agenda

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.

Keywords

Candida Aspergillus Antifungals Echinocandins Fluconazole Beta-d-glucan 

Abbreviations

BDG

β-1 → 3-d-glucan

CAGTA

Candida albicans germ tube antibody

CCPA

Chronic cavitary pulmonary aspergillosis

CFPA

Chronic fibrosing pulmonary aspergillosis

CPA

Chronic pulmonary aspergillosis

ESAT

Empirical systemic antifungal treatment

GM

Galactomannan

HSCT

Halogenic stem cell transplant

IC

Invasive candidiasis

IFI

Invasive fungal infections

IPA

Invasive pulmonary aspergillosis

LAmb

Liposomal amphotericin B

LFD

Lateral flow device

MALDI-TOF MS

Matrix-assisted laser desorption ionization–time of flight mass spectrometry

PCT

Procalcitonin

TDM

Therapeutic drug monitoring

Notes

Compliance with ethical standards

Conflicts of interests

No non-financial conflicts of interest exist for any of the authors.

Financial interest

MB serves on scientific advisory boards for Basilea, Gilead, Pfizer, Merck, and Astellas and has received funding for travel or speaker honoraria from Basilea, Gilead, Pfizer, Merck, and Astellas Pharma. LO has received research grants and/or speaking or consulting fees from Merck, Astellas, Pfizer, Scynexis, Cidara, Gilead, Meiji, and T2 biosystems. AS has served as a speaker for, consultant to, or received research support from Achaogen, Actavis, Astellas, AZ, Bayer, Cempra, Cidara, Entasysis, MedCo, Melinta, Merck, Paratek, Roche, Spero, Tetraphase, Theravamce, and Wockhordt. JFT serves on scientific advisory boards for Merck and Gilead and has received speaker honoraria and/or research grants from Merck, Astellas, and Pfizer. The other authors declare no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2017

Authors and Affiliations

  • Matteo Bassetti
    • 1
    • 16
  • Jose Garnacho-Montero
    • 2
  • Thierry Calandra
    • 3
  • Bartjan Kullberg
    • 4
  • George Dimopoulos
    • 5
  • Elie Azoulay
    • 6
  • Arunaloke Chakrabarti
    • 7
  • Daniel Kett
    • 8
  • Cristobal Leon
    • 9
  • Luis Ostrosky-Zeichner
    • 10
  • Maurizio Sanguinetti
    • 11
  • Jean-Francois Timsit
    • 12
  • Malcom D. Richardson
    • 13
  • Andrew Shorr
    • 14
  • Oliver A. Cornely
    • 15
  1. 1.Infectious Diseases Clinic, Santa Maria Misericordia HospitalUniversity of UdineUdineItaly
  2. 2.Unidad Clínica de Cuidados Intensivos, Hospital Universitario Virgen Macarena and Institute of Biomedicine of SevilleIBiS/CSIC/University of SevillesevilleSpain
  3. 3.Infectious Diseases Service, Department of MedicineCentre Hospitalier Universitaire Vaudois, University of LausanneLausanneSwitzerland
  4. 4.Department of Medicine and Radboud Center for Infectious DiseasesRadboud University Medical CenterNijmegenNetherlands
  5. 5.Department of Critical CareUniversity Hospital ATTIKON, National and Kapodistrian University of AthensAthensGreece
  6. 6.Medical Intensive Care Unit, Hôpital Saint-Louis, ECSTRA Team, Biostatistics and Clinical EpidemiologyParis Diderot Sorbonne UniversityParisFrance
  7. 7.Department of Medical MicrobiologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
  8. 8.Division of Pulmonary and Critical Care MedicineThe Leonard M. Miller School of Medicine at the University of MiamiMiamiUSA
  9. 9.Intensive Care Unit, Hospital Universitario de ValmeUniversidad de SevillaSevilleSpain
  10. 10.Division of Infectious DiseasesMcGovern Medical School, UTHealthHoustonUSA
  11. 11.Institute of MicrobiologyUniversità Cattolica del Sacro CuoreRomeItaly
  12. 12.1UMR1137-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 ICUBichat HospitalParisFrance
  13. 13.Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, Manchester Academic Health Science CentreThe University of ManchesterManchesterUK
  14. 14.Pulmonary and Critical Care MedicineMedstar Washington Hospital CenterWashingtonUSA
  15. 15.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 CologneCologneGermany
  16. 16.Clinica Malattie InfettiveAzienda Sanitaria Universitaria Integrata, Presidio Ospedaliero Santa Maria della MisericordiaUdineItaly

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