Risk Factors

Risk Factors that Predispose to Invasive Fungal Infections*

Invasive fungal infections (IFIs) occur predominantly in immunocompromised individuals but can also be seen in previously well persons. The human innate immune system recognizes key components of the fungal cell wall as foreign resulting in a myriad of signaling cascades. This triggers release of antifungal molecules as well as adaptive immune responses, which kill or at least contain the invading fungi. However, these defenses may fail in hosts with primary or secondary immunodeficiencies resulting in IFIs. A number of risk factors can predispose a patient to Invasive Fungal Infections (IFIs).

*Source: Christina C Chang, Stuart M Levitz, Fungal immunology in clinical practice: Magical realism or practical reality?, Medical Mycology, Volume 57, Issue Supplement_3, June 2019, Pages S294–S306, https://doi.org/10.1093/mmy/myy165

Epidemiological Trends of Invasive Aspergillosis

Patients at Risk for Infection Rising Rapidly

Evolving groups of non-neutropenic patients at risk for Invasive Aspergillosis in the era of (i) targeted “precision-medicine” therapies for the management of malignant, inflammatory, and autoimmune diseases that impact the immune system and (ii) complex metabolic and immunological abnormalities in a large proportion of critically ill patients who survive severe infections in the intensive care unit. ICU, intensive care unit; SMKI, small-molecule kinase inhibitor; CAR T cells, chimeric antigen receptor T cells.*

New Biologic Agents and Fungal Infections*

There has been a proliferation of new biologic agents in clinical practice many of which have been associated with susceptibility to specific and in some cases unusual fungal infections. Keeping pace with these novel agents, particularly their cellular and humoral impact, is challenging. Examples of these agents and their respective fungal susceptibility are reviewed in the table* below:

Inhibitor Mechanism	Biologic Agent Example(s)	Fungal Susceptibility
IL-17A	Secukinumab, Ixekizumab, Brodalumab	Candidiasis
IL-23/IL-17 blockers	Ustekinumab	Mucosal Candidiasis
Janus kinase inhibitors - JAK1/2 and 1/3 inhibitors	Tofacitinib, Ruxolitinib, Baricitinib	Cryptococcosis, Talaromycosis, Candidiasis
Bruton's tyrosine kinase (BTK) inhibitor	Ibrutinib	Cryptococcosis, Aspergillosis, Mucormycosis
Vascular endothelial growth factor (VEGF)	Bevacizumab	Aspergillosis, Fusariosis
α-4/β-7 integrin	Natalizumab, Vedolizumab	Cryptococcosis, Candidiasis
BCR-ABL, c-Kyt, other off-target kinases	Imatinib, Dasatinib, Sorafenib	Candidiasis, PJP, Rhodoturulosis
B cell lymphoma (BCL)-2	Venetoclax	Aspergillosis, Candidiasis, PJP