scholarly journals Invasive Fungal Infections in Infants—Focus on Anidulafungin

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.

2015 ◽  
Vol 7 ◽  
pp. e2015048 ◽  
Author(s):  
Jean Elcheikh

Over the past decade, invasive fungal infections (IFI) have remained an important problem in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined.We conducted a retrospective, bi-institutional comparative clinical study, and compared the efficacy and safety of micafungin 50mg/day (iv) with those of fluconazole (400mg/day) or itraconazole 200mg/day (iv) as prophylaxis for adult patients with various haematological diseases receiving haplo-identical allogeneic stem cell transplantation (haplo).Overall, 99 patients were identified; 30 patients received micafungin, and 69 patients received fluconazole or itraconazole. After a median follow-up of 13 months (range: 5-23), Proven or probable IFIs were reported in 3 patients (10%) in the micafungin group and 8 patients (12%) in the fluconazole or itraconazole group. Fewer patients in the micafungin group had invasive aspergillosis (1 [3%] vs. 5 [7%], P=0.6). A total of 4 (13%) patients in the micafungin group and 23 (33%) patients in the fluconazole or itraconazole group received empirical antifungal therapy (P = 0.14).No serious adverse events related to treatment were reported by patients and there was no treatment discontinuation because of drug-related adverse events in both groups.Despite the retrospective design of the study and limited sample, it contributes reassuring data to confirm results from randomised clinical trials, and to define a place for micafungin in prophylaxis after haplo.


2013 ◽  
Vol 154 (3) ◽  
pp. 83-92
Author(s):  
Mariann Harangi ◽  
Noémi Zsíros ◽  
Lilla Juhász ◽  
György Paragh

Statin therapy is considered to be safe and rarely associated with serious adverse events. However, a significant proportion of patients on statin therapy show some degree of intolerance which can lead to decreased adherence to statin therapy. The authors summarize the symptoms, signs and frequencies of the most common statin-induced adverse effects and their most important risk factors including some single nucleotide polymorphisms and gene mutations. Also, they review the available approaches to detect and manage the statin-intolerant patients. Orv. Hetil., 2013, 154, 83–92.


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.


2021 ◽  
Vol 14 (10) ◽  
pp. 955
Author(s):  
Jen-Yu Hsu ◽  
Yan-Chiao Mao ◽  
Po-Yu Liu ◽  
Kuo-Lung Lai

Some effective drugs have been approved or issued an Emergency Use Authorization for the treatment of COVID-19 in hospitalized patients, but post-market surveillance is warranted to monitor adverse events. We reviewed clinical trials and case reports in patients with moderate-to-severe COVID-19 infection who received remdesivir, baricitinib, tocilizumab, or sarilumab. The drug-specific pharmacokinetics, toxicity, and drug interactions are summarized in this study. Remdesivir and baricitinib are small-molecule drugs that are mainly metabolized by the kidneys, while tocilizumab and sarilumab are monoclonal antibody drugs with metabolic pathways that are currently not fully understood. The most common adverse events of these drugs are alterations in liver function, but serious adverse events have rarely been attributed to them. Only a few studies have reported that remdesivir might be cardiotoxic and that baricitinib might cause thromboembolism. Biological agents such as baricitinib, tocilizumab, and sarilumab could inhibit the pathway of inflammatory processes, leading to immune dysregulation, so the risk of secondary infection should be assessed before prescribing. Further recognition of the pathogenic mechanism and risk factors of adverse events is essential for optimizing treatment strategies.


2020 ◽  
Vol 28 (3) ◽  
pp. 467-473
Author(s):  
Kübra Evren Şahin

Background: This study aims to evaluate the frequency of and associated risk factors for adverse events caused by cardiac catheterization procedures in pediatric patients. Methods: Between January 2009 and January 2012, a total of 599 pediatric patients (320 males, 279 females; mean age 5.4±4.7 years; range, 1 day to 21 years) who underwent cardiac catheterization in our cardiac catheterization laboratory were retrospectively analyzed. Demographic and clinical data of the patients including the duration of the procedure, management of anesthesia, the American Society of Anesthesiologists class, and Catheterization Risk Score for Pediatrics, and procedure-related serious adverse events were recorded. Results: The incidence of procedure-related serious adverse events was 9.18%. Potential risk factors associated with serious adverse events were identified as interventional heart catheterization, high scores obtained from the Catheterization Risk Score for Pediatrics, the use of endotracheal tube in airway control, and prolonged procedural duration. Conclusion: Our study results suggest that prolonged duration of catheterization is a potential risk factor for procedure-related adverse events and the duration of the procedure needs to be included as a variable in the Catheterization Risk Score for Pediatrics scoring system for predicting procedure-related adverse events.


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.


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