Epidemiology and Risk Factors of Invasive Fungal Infections

Author(s):  
Frédéric Lamoth
2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S576-S577
Author(s):  
Thomas Holowka ◽  
Harry Cheung ◽  
Maricar F Malinis ◽  
Sarah Perreault ◽  
Iris Isufi ◽  
...  

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


2021 ◽  
Vol 7 (2) ◽  
pp. 156
Author(s):  
Will Garner ◽  
Palash Samanta ◽  
Ghady Haidar

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.


Blood ◽  
2018 ◽  
Vol 131 (17) ◽  
pp. 1955-1959 ◽  
Author(s):  
David Ghez ◽  
Anne Calleja ◽  
Caroline Protin ◽  
Marine Baron ◽  
Marie-Pierre Ledoux ◽  
...  

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.


2013 ◽  
Vol 7 ◽  
pp. CMPed.S8028 ◽  
Author(s):  
Michael H. Wilke

Introduction Invasive fungal infection in pediatric intensive care units (PICU) is a rising challenge. Candida species are the most common microorganisms in these infections. Due to growing resistance against fluconazole, echinocandins are being used for the appropriate therapy. However, the recent IDSA guidelines recommend them only in cases where fluconazole or Amphotericin B cause treatment failure or are contraindicated. In a literature review, the importance of invasive fungal infections in PICU settings and the role of anidulafungin shall be examined. Materials and Methods Articles were retrieved form PubMed covering the years 2000–2012. Various search terms were used. Then the articles were clustered in different types like ‘review,’ ‘pharmacokinetics,’ ‘case reports’ and others. Results From 67 search results, 14 articles were selected. Of these, 7 were related to anidulafungin, while 7 were related to echinocandins or fungal infections in the PICU. Anidulafungin was examined in 4 PK/PD studies where a good safety profile was found. No serious adverse events occurred. The articles reporting risk factors show that central venous catheters, receipt of antibiotics, receipt of parenteral nutrition, and neutropenia are the most important independent risk factors for invasive fungal infections in PICU. Three reviews of antifungal agents show that echinocandins may be useful due to their safety profile; micafungin is the best examined one and further trials are needed. Discussion The published literature on invasive fungal infections in PICU settings has grown over the years. There are only a few articles, however, which are directly related to the use of anidulafungin in this setting. A most recent publication showed good PK/PD dynamics and a good safety profile for anidulafungin. So far, no RCT in the area of invasive candidiasis in infants and neonates has been published. A review of currently registered trials at ClinicalTrials.gov has shown one more trial related to PK/PD and two trials that investigate the use of anidulafungin or anidulafungin in combination with Voriconazole in pediatrics. Conclusion The small body of existing literature on anidulafungin in infants shows success in treatment, no drug-related adverse events, and good pharmacodynamics. A dosing of 0.75 mg/kg/day or 1.5 mg/kg/day is as effective as 50 mg/day or 100 mg/day in adults. More trials on the use in clinical reality of PICU or NICU should follow.


Author(s):  
Vikas Devra ◽  
Varsha Varshney

Background: COVID 19 or severe acute respiratory syndrome (SARS-CoV-2) evolved as global pandemic since December 2019 when it was first reported in Wuhan, China. Coinfection in patients with COVID-19 has been reported in multiple studies, being bacterial in origin the most frequent; and fungal infection being reported only in severe cases. Methods: This study was conducted at the department of E.N.T. at PanditDeenDayalUpadhyay Medical College, Churu. Cases presented to E.N.T. OPD with clinical features of invasive rhino-orbital fungal infection for the period of two month from 1st June 2021 were included in the study. Patients were clinically evaluated, HRCT, MRI scans and with KOH mount and culture of involved tissue ere done. Patient’s COVID-19 status was ascertained. The clinicopathological association of occurrence of invasive fungal infections in post covid and non-covid patients along with other risk factors like diabetes mellitus, immune compromised state and long-term steroid use was done using statistical methods Results: We studied 21 patients who attended our OPD with features of invasive fungal infection. Most common presentation was swelling and pain in the cheek region and red eye and swelling around the eye, three patients presented with maxillary swelling with blackish discoloration of teeth. Radiological findings were suggestive of fungal etiology in all patients. KOH mount showed fungal hyphae in 20 cases. Total 20 cases were post COVID status. Old DM was there in 12 patients whereas 9 patients showed new onset hyperglycemia. Conclusions: COVID-19 is associated with a significant incidence of secondary infections, both bacterial and fungal probably due to immune dysregulation. The widespread use of steroids/monoclonal antibodies/broad-spectrum antibiotics as part of the management protocols against COVID-19 may lead to the exacerbation of preexisting fungal diseases or development of new infection. Treating Physicians should make themselves aware and prepare for the possibility of invasive secondary fungal infections in patients with COVID-19 infection especially in patients with preexisting risk factors and should enable early diagnosis and treatment with the subsequent reduction of mortality and morbidity. Keywords: Coronavirus, COVID-19, mucormycosis, invasive fungal infections


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