#78: Use of Isavuconazonium for Treatment Of Invasive Fungal Infection in Immunocompromised Pediatric Patients

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S2-S2
Author(s):  
Sindhu Mohandas ◽  
Kanokporn Mongkolrattanothai ◽  
Leslie Stach ◽  
Regina Orbach ◽  
Michael Neely
Keyword(s):  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Liposomal Amphotericin ◽  
Fungal Pathogens ◽  
Pediatric Patients ◽  
Therapeutic Option ◽  
Dual Therapy ◽  
Primary Diagnosis ◽  
Cardiac Transplant ◽  
Serum Concentrations

Abstract Background Isavuconazole (ISZ), dosed as the pre-drug isavuconazonium (ISM), is active against a wide variety of clinically important fungal pathogens. ISM is approved for the treatment of invasive aspergillosis and mucormycosis in adults ≥18 years of age. We present our experience with ISM to treat proven or probable fungal infection in immunocompromised pediatric patients. Methods Retrospective review of patients who received ISM at our institution between April 2016 and April 2019, we abstracted demographic information, primary diagnosis, indication for ISM therapy, ISZ serum concentrations if available, and outcomes. Results Of 14 patients who received ISM, 11 were ≤18 years of age (range 6–18 years). Underlying conditions included leukemia (n = 7), lymphoma (n = 1), post BMT (n = 1), diabetes (n = 1), and cardiac transplant (n = 1). Nine (82%) had proven invasive fungal infection (IFI) with aspergillosis (n = 2), zygomycosis (n = 3), mixed aspergillosis and zygomycosis (n = 2), mixed Rhizopus and Scedosporium (n = 1), and pathology only (n = 1) and 2 had probable IFI. Five of these 11 patients received combination ISM and liposomal amphotericin initially and the other 6 received liposomal amphotericin with or without other azoles prior to changing to ISM monotherapy. This was followed by monotherapy with ISM in 10 patients after a mean of 26 days (range 6–63) and continued dual therapy in the one. ISM dosing was 10 mg/kg q8h on days 1 and 2, followed by q24 thereafter, up to a maximum of 372 mg/dose. There were 19 measured ISZ serum concentrations obtained from 8 patients after >1 week of verified inpatient dosing, ranging from 1.0 to 7.5 mg/L, above the MIC in all cases when known. Three (27%) patients died of underlying non-mycological causes, 1 (9%) died of progressive scedosporiosis, and 7 (64%) improved. ISM was well tolerated with no dose-limiting, drug-related toxicities noted. Conclusions ISM is a well-tolerated therapeutic option in pediatric patients at risk for or with invasive mycosis. Only 1 of our 11 patients died from progressive fungal disease.

scholarly journals 2122. Isavuconazonium for Invasive Fungal Therapy: Single-Center Pediatric Experience

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S718-S718
Author(s):  
Kanokporn Mongkolrattanothai ◽  
Sindhu Mohandas ◽  
Leslie Stach ◽  
Regina Orbach ◽  
Michael Neely
Keyword(s):  
Fungal Infection ◽  
Liposomal Amphotericin ◽  
Fungal Pathogens ◽  
Pediatric Patients ◽  
Therapeutic Option ◽  
Dual Therapy ◽  
Primary Diagnosis ◽  
Cardiac Transplant ◽  
Serum Concentrations ◽  
Patients At Risk

Abstract Background Isavuconazole (ISZ), dosed as the pre-drug isavuconazonium (ISM), is active against a wide variety of clinically important fungal pathogens. ISM is approved for the treatment of invasive aspergillosis and mucormycosis in adults ≥18 years of age. We present our experience with ISM to treat proven or to prevent fungal infection in pediatric patients. Methods In a retrospective review of patients who received ISM at our institution between April 2016 and April 2019, we abstracted demographic information, primary diagnosis, indication for ISM therapy, ISZ serum concentrations if available, and outcomes. Results Of 16 patients who received ISM, 12 were < 18 years of age (range 6–17 years). Underlying conditions included leukemia (n = 8), lymphoma (n = 1), post BMT (n = 1), diabetes (n = 1), and cardiac transplant (n = 1). Nine (75%) had proven invasive fungal infection with aspergillosis (n = 2), zygomycosis (n = 3), mixed aspergillosis and zygomycosis (n = 2), mixed Rhizopus and Scedosporium (n = 1), and pathology only (n = 1). Five of these 9 patients received combination ISM and liposomal amphotericin initially, followed by monotherapy with ISM in 4 patients after a mean of 26 days (range 6–63), and continued dual therapy in the fifth. The other 4 received liposomal amphotericin with or without other azoles prior to changing to ISM monotherapy. ISM dosing was 10 mg/kg q8h on days 1 and 2, followed by q24 thereafter, up to a maximum of 372 mg/dose. There were 19 measured ISZ serum concentrations obtained from 8 patients after >1 week of verified inpatient dosing, ranging from 1.0 to 7.5 mg/L, above the MIC in all cases when known. Five (42%) patients died of underlying non-mycological causes, 1 (8%) died of progressive scedosporiosis, and 6 (50%) improved. The two patients receiving ISM prophylaxis did not suffer a breakthrough fungal infection. ISM was well tolerated with no dose-limiting, drug-related toxicities noted. Conclusion ISM is a well-tolerated therapeutic option in pediatric patients at risk for or with invasive mycosis. Only 1 of our 12 patients died from progressive fungal disease. Disclosures All authors: No reported disclosures.

Haemopoietic Cell Transplantation of Patients with a History of Deep or Invasive Fungal Infection during Prophylaxis with Liposomal Amphotericin B

2005 ◽  
Vol 113 (2) ◽  
pp. 104-108 ◽  
Author(s):  
William H. Krüger ◽  
Bettina Rüssmann ◽  
Maike de Wit ◽  
Nicolaus Kröger ◽  
Helmut Renges ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Amphotericin B ◽  
Cell Transplantation ◽  
Invasive Fungal Infection ◽  
Liposomal Amphotericin ◽  
Liposomal Amphotericin B ◽  
History Of

The Clinical Feature of Invasive Fungal Infection in Pediatric Patients With Hematologic and Malignant Diseases

2008 ◽  
Vol 30 (12) ◽  
pp. 886-890 ◽  
Author(s):  
Ryoji Kobayashi ◽  
Makoto Kaneda ◽  
Tomonobu Sato ◽  
Mizuho Ichikawa ◽  
Daisuke Suzuki ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Pediatric Patients ◽  
Clinical Feature ◽  
Malignant Diseases

scholarly journals 78. Non-Invasive Prediction of Invasive Fungal Infection by Plasma-Based Microbial Cell-Free DNA Next-Generation Sequencing (mcfDNA NGS) in Pediatric Patients with Relapsed or Refractory Leukemia

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S51-S51
Author(s):  
Joshua Wolf ◽  
Joshua Wolf ◽  
Gabriela Maron ◽  
Kathryn Goggin ◽  
Kim J Allison ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Fungal Pathogen ◽  
Pediatric Patients ◽  
Hematopoietic Cell Transplantation ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Non Invasive ◽  
Clinical Onset ◽  
Fungal Dna

Abstract Background Diagnosis of invasive fungal infections (IFIs), a life-threatening complication of cancer therapy or hematopoietic cell transplantation (HCT) can be challenging, and IFI has poor outcomes. Prediction or early non-invasive diagnosis of IFI in high-risk hosts before onset of symptoms could reduce morbidity and mortality. Because non-invasive plasma mcfDNA NGS can detect invasive fungal infections, and may predict bloodstream infections in immunocompromised patients, we hypothesized that mcfDNA NGS might also predict invasive fungal infection before clinical presentation. Methods In a prospective study, serial remnant plasma samples were collected from pediatric patients undergoing treatment for relapsed or refractory leukemia. IFI events were classified according to EORTC criteria by 2 independent experts, and episodes empirically treated for suspected IFI, but not meeting ‘possible’ criteria were classified as ‘suspected’. All samples collected within 30 days before clinical diagnosis of non-fungemic IFI were tested for fungal DNA by mcfDNA NGS using a research-use only assay by Karius, Inc. optimized for fungi; because of overlapping clinical syndromes, non-fungal DNA was not considered in this study. Results There were 15 episodes of suspected IFI in 14 participants with ≥1 sample available from either diagnostic (within 1 day of diagnosis) or predictive (2 to 30 days prior to diagnosis) periods (5 “suspected”, and 4 probable and 6 proven by EORTC definitions). Of 10 probable or proven IFIs, 6 (60%) had a relevant fungal pathogen identified mcfDNA NGS at diagnosis. In each of these cases the fungal DNA was also detectable prior to clinical onset of IFI (Range 2 to 41 days; Figure 1). In an additional case, manual review of sequence data identified the fungal DNA at diagnosis and during the prior month. Of 5 “suspected” IFI episodes, all were determined by expert review as not representing fungal infection; fungal DNA was identified by mcfDNA NGS in 2/54 (3.7%) of samples from these episodes. Table 1. Characteristics of Invasive Fungal Infections Conclusion mcfDNA NGS can identify fungal pathogen DNA before clinical onset of IFI, so might predict IFI in immunocompromised hosts, and may help differentiate fungal infection from other etiologies of lung nodules or infiltrates. Disclosures Joshua Wolf, MBBS, PhD, FRACP, Karius Inc. (Research Grant or Support) Joshua Wolf, MBBS, PhD, FRACP, Nothing to disclose Radha Duttagupta, PhD, Karius inc (Employee) Lily Blair, PhD, Karius Inc. (Employee) Asim A. Ahmed, MD, Karius, Inc. (Employee)

Risk Analysis for Invasive Fungal Infection after Living Donor Liver Transplantation: Which Patient Needs Potent Prophylaxis?

2018 ◽  
Vol 36 (1) ◽  
pp. 59-66
Author(s):  
Masashi Utsumi ◽  
Yuzo Umeda ◽  
Takahito Yagi ◽  
Takeshi Nagasaka ◽  
Susumu Shinoura ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Analysis ◽  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Fungal Pathogens ◽  
Living Donor ◽  
Donor Liver ◽  
Candida Spp ◽  
Donor Liver Transplantation ◽  
Post Transplant

Background: Invasive fungal infection (IFI) is associated with high mortality after living donor liver transplant (LDLT). The aim of this study was to identify the risk factors for post-LDLT IFI for early diagnosis and improvement of antifungal treatment outcome. Methods: Risk analysis data were available for all 153 patients who underwent LDLT between January 2005 and April 2012. Results: During the follow-up period (1,553 ± 73 days, range 20–2,946 days), 15 patients (9.8%) developed IFI classified as “proven” (n = 8) and “probable” (n = 7) with fungal pathogens including Candida spp. (n = 10), Aspergillus spp. (n = 4), and Trichosporon (n = 2). Of these patients, 7 patients with IFI died despite treatment. The 1-, 3-, and 5-year survival rates were lower in patients with IFI than those without IFI (66.7/59.3/44.4 vs. 90.4/85.7/81.8%, respectively; p = 0.0026). Multivariate analysis identified model for end-stage liver disease score of ≥26 (OR 16.0, p = 0.0012) and post-transplant acute kidney injury (RIFLE criteria I- or F-class; OR 4.87, p = 0.047) as independent risk factors for IFI. Conclusion: Preoperative recipients’ status and postoperative kidney dysfunction can affect an occurrence of post-transplant IFI. These risk factors would be taken into consideration for designation of proper antifungal therapy.

scholarly journals Continuous Infusion Vancomycin in Pediatric Patients: A Critical Review of the Evidence

2020 ◽  
Vol 25 (3) ◽  
pp. 198-214
Author(s):  
Heather L. Girand
Keyword(s):  
Continuous Infusion ◽  
English Language ◽  
Pediatric Patients ◽  
Randomized Clinical Trials ◽  
Therapeutic Option ◽  
Study Data ◽  
Cochrane Library ◽  
Serum Concentrations ◽  
Continuous Administration ◽  
Optimal Dosing

OBJECTIVE To evaluate the use of continuous infusion vancomycin in pediatric patients. DATA SOURCES AND STUDY SELECTION PubMed, Cochrane Library, International Pharmaceutical Abstracts, and Google Scholar were searched to identify relevant published articles (1977 to November 2019) using the following search terms: vancomycin, neonates, pediatrics, infusion, continuous, administration, children, nephrotoxicity, pharmacokinetics, and pharmacodynamics. All English-language primary references that evaluated continuous infusion vancomycin in pediatric patients were included in this review. DATA SYNTHESIS Vancomycin is typically administered with intermittent infusions, but continuous infusion is an alternative delivery method used to improve achievement of target serum concentrations. Fifteen articles were reviewed that evaluated continuous infusion vancomycin in pediatric patients. Study data were heterogeneous with limited evidence to support improved clinical or microbiologic outcomes as compared with intermittent dosing. Potential benefits and limitations of continuous infusions are discussed. CONCLUSIONS Currently available evidence is lacking to support routine implementation of continuous infusion vancomycin in pediatric patients. However, it is a therapeutic option in certain clinical conditions and could be beneficial for individuals with serious Gram-positive infections where rapid achievement of target serum concentrations is critical. Continuous infusions may also benefit individuals who do not achieve target concentrations or who experience significant red man syndrome with traditional dosing, particularly when high daily doses are required. Optimal dosing and ideal target serum concentrations have not been established and may vary for different populations. Future prospective randomized clinical trials should be performed to identify optimal dosing and monitoring regimens and determine comparative safety and efficacy with traditional intermittent dosing in various pediatric populations.

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