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Drugs

, Volume 68, Issue 14, pp 1941–1962 | Cite as

Patients at High Risk of Invasive Fungal Infections

When and How to Treat
  • Maria J. G. T. Rüping
  • Jörg J. Vehreschild
  • Oliver A. Cornely
Therapy In Practice

Abstract

When and how to treat invasive fungal infections (IFIs) is discussed in this review, with a focus on the two most prevalent non-endemic IFIs, namely invasive aspergillosis and invasive candidiasis. Early treatment initiation in patients with IFIs has a profound impact on mortality rates, but reliable diagnostic measures are lacking. This situation has led to the parallel use of different treatment strategies, e.g. prophylaxis, empirical and pre-emptive treatment, as well as targeted treatment in response to a definite diagnosis of IFI. Identifying high-risk patients is the first step in reducing IFI-related mortality. Patients at risk of invasive aspergillosis comprise (i) those with acute myelogenous leukaemia (AML) or myelodysplastic syndrome (MDS) during remission induction chemotherapy; (ii) patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT); (iii) recipients of solid organ transplants; and (iv) those with other conditions of severe and prolonged immunosuppression. Patients at high risk of invasive candidiasis are less well defined. Risk factors are diverse and include haematological malignancy, neutropenia, age <1 month or >65 years, and recent abdominal surgery. The individual risk further depends on the presence of a variety of other risk factors, including central venous catheters, use of broad spectrum antibacterials, prolonged intensive care unit (ICU) stay, total parenteral nutrition, mucosal Candida spp. colonization and renal failure.

Extensive research has been conducted to facilitate the best possible treatment strategies for these severe infections. Optimal timing and choice of antifungal agents largely remain a matter of controversy. After having reviewed the major clinical trials, we conclude that comparisons between different treatment strategies cannot be made, neither at present nor in the near future. The complexity of the clinical problem leads to an eclectic treatment approach to reduce morbidity and mortality from IFIs without compromising tolerability. We recommend prophylaxis with posaconazole for allogeneic HSCT recipients, patients receiving induction chemotherapy for AML or MDS, and those undergoing immunosuppressive therapy for graft-versus-host disease after allogeneic HSCT. For the empirical treatment of persistently febrile neutropenia, caspofungin is our first-and liposomal amphotericin B deoxycholate (LAmB) our second-line choice. Once a diagnosis of invasive aspergillosis has been established, voriconazole should be the preferred treatment option, with LAmB being an alternative. Fluconazole prophylaxis for invasive candidiasis should remain restricted to high-risk ICU patients. Once a diagnosis has been established, the drug of choice for adequate treatment depends largely on neutrophil count and haemodynamic stability. In non-neutropenic patients, an echinocandin should be considered the first-line treatment option, while patients with susceptible Candida spp. may be switched to fluconazole. In neutropenic patients, caspofungin or micafungin might be preferred to anidulafungin as first-line treatment. LAmB is a second-line treatment option in both settings.

Early diagnosis of IFIs is imperative to facilitate treatment success. In all patients at risk for IFIs, blood cultures, galactomannan antigen and diagnostic imaging should be rigorously enforced.

Keywords

Fluconazole Voriconazole Intensive Care Unit Patient Invasive Aspergillosis Caspofungin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors did not receive any funding or external help for the completion of this article. Dr Rüping has received travel grants from Schering-Plough/Essex and Gilead. Dr Vehreschild has received travel grants from Merck Sharp & Dohme/Merck, Pfizer, Schering-Plough and Viropharma. Dr Cornely is supported by the German Federal Ministry of Research and Education (BMBF grant 01KN0706) and has received research grants from, is an advisor to, or served at the speakers’ bureau of Astellas, Basilea, Bayer, F2G, Genzyme, Gilead, Pfizer, Merck, Mölnlycke, Nektar, Optimer, Schering-Plough, SpePharm, United Medical, Vicuron and Zeneus.

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Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Maria J. G. T. Rüping
    • 1
  • Jörg J. Vehreschild
    • 1
  • Oliver A. Cornely
    • 1
    • 2
  1. 1.Department I of Internal Medicine, Clinical Trials Unit Infectious Diseases IIHospital of the University of CologneCologneGermany
  2. 2.Clinical Trials Center CologneHospital of the University of CologneCologneGermany

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