Distribution of invasive fungal infections: Molecular epidemiology, etiology, clinical conditions, diagnosis and risk factors: A 3-year experience with 490 patients under intensive care

Abstract Background Ibrutinib is a tyrosine kinase inhibitor used to treat hematologic malignancies that may increase the risk of serious infection including invasive fungal infections (IFI). In a study of 378 patients with hematologic malignancy on ibrutinib, serious infection and IFI occurred in 11% and 4% respectively (Varughese et al. Clin Infect Dis). The primary aims of our study were to determine the incidence of serious infection and associated risk factors in patients on ibrutinib. Methods We performed a retrospective analysis of patients with hematologic malignancy prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital from 2014 to 2019 to identify serious infections defined as those requiring inpatient management. We collected demographic, clinical and oncologic data. Chi-squared tests were used to determine factors associated with an increased risk of infection. Results A total of 254 patients received ibrutinib including 156 with CLL, 89 with NHL and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. There were 51 (20%) patients with serious infections including 45 (17.7%) bacterial, 9 (3.5%) viral and 5 (2%) IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis). Anti-mold prophylaxis was prescribed to 7 (2.8%) patients, none of whom developed IFI. Risk factors associated with serious infection included ECOG score ≥ 2 (OR 4.6, p < 0.001), concurrent steroid use (≥ 10 mg prednisone daily for ≥ 2 weeks; OR 3.0, p < 0.001), neutropenia (OR 3.6, p < 0.01), lymphopenia (OR 2.4, p < 0.05) and maximum ibrutinib dose of 560 mg (OR 2, p < 0.05). There was a dose dependent increase in infections based on number of chemotherapy regimens prior to ibrutinib initiation: 14.3% with 0, 19.7% with 1-2 and 28.7% with ≥ 3 prior treatments. Conclusion The incidence of serious infection in hematologic patients on ibrutinib was higher than previously reported (20% versus 11%) but the rate of IFI was lower (2% versus 4%). High ECOG score, leukopenia, steroids, and higher ibrutinib doses were associated with an increased risk for serious infection. Targeted antimicrobial prophylaxis should be considered for patients on ibrutinib with these risk factors. Improving functional status may also reduce the risk of infection in patients on ibrutinib. Disclosures All Authors: No reported disclosures

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Invasive Fungal Infections after Anti-CD19 Chimeric Antigen Receptor-Modified T-Cell Therapy: State of the Evidence and Future Directions

Journal of Fungi ◽

10.3390/jof7020156 ◽

2021 ◽

Vol 7 (2) ◽

pp. 156

Author(s):

Will Garner ◽

Palash Samanta ◽

Ghady Haidar

Keyword(s):

Risk Factors ◽

T Cell ◽

Cell Therapy ◽

Chimeric Antigen Receptor ◽

Fungal Infections ◽

Antigen Receptor ◽

Invasive Fungal Infections ◽

T Cell Therapy ◽

Car T Cell ◽

Car T

Studies describing invasive fungal infections (IFIs) after chimeric antigen receptor-modified T-cell (CAR-T-cell) therapy are limited. Although post-CAR-T-cell IFIs appear to be uncommon, they are associated with significant morbidity and mortality. Specific risk factors for IFIs in CAR-T-cell recipients have not been fully characterized and are often extrapolated from variables contributing to IFIs in patients with other hematologic malignancies or those undergoing hematopoietic cell transplant. Optimal prophylaxis strategies, including the use of yeast versus mold-active azoles, also remain ill-defined. Further research should investigate key risk factors for IFIs and establish an evidence-based approach to antifungal prophylaxis in these patients in order to improve clinical outcomes.

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Prevalence and impact of invasive fungal infections in intensive care

Critical Care ◽

10.1186/cc12026 ◽

2013 ◽

Vol 17 (S2) ◽

Author(s):

JM Patel ◽

K Couper ◽

T Melody ◽

R O'Brien ◽

D Parekh

Keyword(s):

Intensive Care ◽

Fungal Infections ◽

Invasive Fungal Infections

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Invasive fungal infections in the intensive care unit: a multicentre, prospective, observational study in Italy (2006-2008)

Mycoses ◽

10.1111/j.1439-0507.2011.02044.x ◽

2011 ◽

Vol 55 (1) ◽

pp. 73-79 ◽

Cited By ~ 76

Author(s):

Anna Maria Tortorano ◽

Giovanna Dho ◽

Anna Prigitano ◽

Giuseppe Breda ◽

Anna Grancini ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Observational Study ◽

Prospective Observational Study ◽

Fungal Infections ◽

Invasive Fungal Infections

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Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib

Blood ◽

10.1182/blood-2017-11-818286 ◽

2018 ◽

Vol 131 (17) ◽

pp. 1955-1959 ◽

Cited By ~ 114

Author(s):

David Ghez ◽

Anne Calleja ◽

Caroline Protin ◽

Marine Baron ◽

Marie-Pierre Ledoux ◽

...

Keyword(s):

Risk Factors ◽

Invasive Aspergillosis ◽

Early Onset ◽

Fungal Infections ◽

Invasive Fungal Infections ◽

Key Points

Key Points Ibrutinib may be associated with invasive fungal infections especially IA. Most infections usually occur during the first months of treatment, often in patients with other risk factors for fungal infections.

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Identification and in Vitro Susceptibility Pattern of Fungal Pathogens in Immunocompromised Patients with invasive Fungal Infections

10.51429/ejmm30317 ◽

2021 ◽

Vol 30 (3) ◽

pp. 127-134

Author(s):

Shaimaa A.S. Selem ◽

Neveen A. Hassan ◽

Mohamed Z. Abd El-Rahman ◽

Doaa M. Abd El-Kareem

Keyword(s):

Intensive Care ◽

Fungal Infection ◽

Fungal Pathogens ◽

Fungal Infections ◽

Antifungal Susceptibility ◽

Invasive Fungal Infections ◽

Immunocompromised Patients ◽

University Hospitals ◽

Vitek 2

Background: In intensive care units, invasive fungal infections have become more common, particularly among immunocompromised patients. Early identification and starting the treatment of those patients with antifungal therapy is critical for preventing unnecessary use of toxic antifungal agents. Objective: The aim of this research is to determine which common fungi cause invasive fungal infection in immunocompromised patients, as well as their antifungal susceptibility patterns in vitro, in Assiut University Hospitals. Methodology: This was a hospital based descriptive study conducted on 120 patients with clinical suspicion of having fungal infections admitted at different Intensive Care Units (ICUs) at Assiut University Hospitals. Direct microscopic examination and inoculation on Sabouraud Dextrose Agar (SDA) were performed on the collected specimens. Isolated yeasts were classified using phenotypic methods such as chromogenic media (Brilliance Candida agar), germ tube examination, and the Vitek 2 system for certain isolates, while the identification of mould isolates was primarily based on macroscopic and microscopic characteristics. Moulds were tested in vitro for antifungal susceptibility using the disc diffusion, and yeast were tested using Vitek 2 device cards. Results: In this study, 100 out of 120 (83.3%) of the samples were positive for fungal infection. Candida and Aspergillus species were the most commonly isolated fungal pathogens. The isolates had the highest sensitivity to Amphotericin B (95 %), followed by Micafungin (94 %) in an in vitro sensitivity survey. Conclusion: Invasive fungal infections are a leading cause of morbidity and mortality in immunocompromised patients, with Candida albicans being the most frequently isolated yeast from various clinical specimens; however, the rise in resistance, especially to azoles, is a major concern.

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