Fungal Infections with Ibrutinib and Other Small-Molecule Kinase Inhibitors

  • Marissa A. Zarakas
  • Jigar V. Desai
  • Georgios Chamilos
  • Michail S. LionakisEmail author
Fungal Genomics and Pathogenesis (S Shoham, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Fungal Genomics and Pathogenesis


Purpose of Review

Small-molecule kinase inhibitors (SMKIs) have revolutionized the management of malignant and autoimmune disorders. Emerging clinical reports point towards an increased risk for invasive fungal infections (IFIs) in patients treated with certain SMKIs. In this mini-review, we highlight representative examples of SMKIs that have been associated with or are expected to give rise to IFIs.

Recent Findings

The clinical use of the Bruton’s tyrosine kinase inhibitor ibrutinib as well as other FDA-approved SMKIs has been associated with IFIs. The fungal infection susceptibility associated with the clinical use of certain SMKIs underscores their detrimental effects on innate and adaptive antifungal immune responses.


The unprecedented development and clinical use of SMKIs is expected to give rise to an expansion of iatrogenic immunosuppressive factors predisposing to IFIs (and other opportunistic infections). Beyond increased clinical surveillance, better understanding of the pathogenesis of SMKI-associated immune dysregulation should help in devising improved risk stratification and prophylaxis strategies in vulnerable patients.


Invasive fungal infections Small-molecule kinase inhibitors Ibrutinib Aspergillosis Pneumocystis jirovecii pneumonia Cryptococcosis 


Funding Information

This work was supported by the Division of Intramural Research (DIR) of the NIAID, NIH.

Compliance With Ethical Standards

Conflict of Interest

Marissa Zarakas, Jigar Desai, Georgios Chamilos, and Michail Lionakis declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2019

Authors and Affiliations

  • Marissa A. Zarakas
    • 1
  • Jigar V. Desai
    • 1
  • Georgios Chamilos
    • 2
    • 3
  • Michail S. Lionakis
    • 1
    Email author
  1. 1.Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaUSA
  2. 2.Department of Clinical Microbiology and Microbial Pathogenesis, School of MedicineUniversity of CreteHeraklionGreece
  3. 3.Institute of Molecular Biology and BiotechnologyFoundation for Research and TechnologyHeraklionGreece

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