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

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.

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S2-S2
Author(s):  
Sindhu Mohandas ◽  
Kanokporn Mongkolrattanothai ◽  
Leslie Stach ◽  
Regina Orbach ◽  
Michael Neely

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 &gt;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.


2020 ◽  
Vol 25 (3) ◽  
pp. 198-214
Author(s):  
Heather L. Girand

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.


DICP ◽  
1989 ◽  
Vol 23 (12) ◽  
pp. 984-987 ◽  
Author(s):  
James E. Tisdale ◽  
Kathleen A. Stringer ◽  
Matthew Antalek ◽  
George E. Matthews

Streptokinase is a thrombolytic agent used most commonly for the dissolution of thrombi obstructing coronary arteries during acute myocardial infarction (MI). Anaphylactic reactions induced by streptokinase occur rarely. We report the case of a patient with acute MI who developed anaphylaxis shortly after the initiation of an intravenous infusion of streptokinase. The patient became profoundly hypotensive and developed an erythematous rash that spread rapidly to cover most of his body. He required mechanical ventilation and the administration of epinephrine for blood pressure support, which succeeded after dopamine and norepinephrine had failed. Streptokinase-induced anaphylaxis is thought to be mediated by immunoglobulin E (IgE), and patients who develop this adverse reaction have been shown to have higher serum concentrations of IgE to streptokinase than those who do not. Epinephrine is the agent of choice for the management of hypotension associated with anaphylaxis. Little evidence exists to support the routine pretreatment of patients who are to receive streptokinase with corticosteroids and/or antihistamines. Streptokinase skin testing may be a useful and accurate means of identifying patients at risk for streptokinase-induced anaphylaxis. Further investigation is required to determine the appropriateness of skin testing in streptokinase therapy.


Author(s):  
Laura Fletcher ◽  
Tammy Pham ◽  
Maguire Herriman ◽  
Bridget Kiely ◽  
Ruth Milanaik

2000 ◽  
Vol 13 (8) ◽  
pp. 860-868 ◽  
Author(s):  
Ichiro Mitsuhara ◽  
Hiroki Matsufuru ◽  
Masahiro Ohshima ◽  
Hisatoshi Kaku ◽  
Yuki Nakajima ◽  
...  

We demonstrate here that induced expression of sarcotoxin IA, a bactericidal peptide from Sarcophaga peregrina, enhanced the resistance of transgenic tobacco plants to both bacterial and fungal pathogens. The peptide was produced with a modified PR1a promoter, which is further activated by salicylic acid treatment and necrotic lesion formation by pathogen infection. Host resistance to infection of bacteria Erwinia carotovora subsp. carotovora and Pseudomonas syringae pv. tabaci was shown to be dependent on the amounts of sarcotoxin IA expressed. Since we found antifungal activity of the peptide in vitro, transgenic seedlings were also inoculated with fungal pathogens Rhizoctonia solani and Pythium aphanidermatum. Transgenic plants expressing higher levels of sarcotoxin were able to withstand fungal infection and remained healthy even after 4 weeks, while control plants were dead by fungal infection after 2 weeks.


2017 ◽  
Vol 2 (1) ◽  
pp. 55-70
Author(s):  
Magda Mohsen ◽  
Omayma OKby ◽  
Reda Elfeshawy

2014 ◽  
Vol 19 (3) ◽  
pp. 182-188
Author(s):  
Lea S. Eiland ◽  
Kalyani B. Sonawane

OBJECTIVES: With an increase in vancomycin resistance and the prevalence of obesity in children, alterations of vancomycin dosing regimens may be necessary to achieve target serum concentrations. The primary objective of this study was to describe initial vancomycin dosing with resulting serum concentrations in healthy-weight and overweight/obese children. Secondary objectives include comparing vancomycin dosing regimens of healthy-weight and overweight/obese patients that produced target trough serum concentrations and evaluating the likelihood of attaining target concentrations by patient characteristics. METHODS: This retrospective review evaluated healthy-weight and overweight/obese patients, aged 2 to 18 years, who had vancomycin trough serum concentrations obtained between 2005 and 2010. Vancomycin dosing, initial trough serum concentrations, pharmacokinetic parameters, and patient demographics were collected for analysis. Target trough serum concentrations were defined as 10 to 20 mg/L. RESULTS: The study included 98 patients (48 healthy weight, 50 overweight/obese) of which only 14 patients (14.2%, 6 healthy weight, 8 obese) reached a target trough serum concentration with empiric dosing. No difference was found between the mean daily dosing of vancomycin that produced target trough serum concentrations in healthy-weight or overweight/obese patients (53.63 mg/kg/day vs 51.6 mg/kg/day, respectively). Demographic or clinical characteristics were not found to be associated with the likelihood of target trough serum concentration attainment. CONCLUSIONS: Vancomycin dosing in healthy-weight and overweight/obese pediatric patients did not reach target trough serum concentrations most of the time. In obtaining initial target serum concentrations, no dosing difference was identified for overweight/obese patients compared with healthy-weight patients. Alternate dosing strategies, therapeutic monitoring, and clinical outcomes should continue to be evaluated in this population.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii422-iii423
Author(s):  
Judy Tran ◽  
Jennifer Holt ◽  
Danielle Crump ◽  
Anita Shea ◽  
Lin Whetzel ◽  
...  

Abstract BACKGROUND In the pediatric population, the probability of compliance with radiation involves multifactorial elements. Younger pediatric patients often require anesthesia to ensure accurate delivery of radiotherapy. The purpose of this analysis was to refine our algorithm in pediatric patients to better identify children who would benefit from behavioral training and/or anxiolyxis intervention with the goal of minimizing anesthesia use. METHOD Retrospective data was collected from electronic medical records from 150 pediatric oncology patients &lt;18 years old, treated with photon and proton radiation at our center from August 2016 to December 2019. We identified potential socio-developmental treatment factors thought to impact behavioral compliance and categorized risk factors based on an algorithm to determine risk for noncompliance with radiotherapy. RESULTS Six categories demonstrated statistical significance (p&lt;0.05) in their influence on behavioral compliance during radiotherapy: age category (specifically age &lt;7: Odds ratio [OR] 3.0, 95% Confidence Interval [CI] 1.0, 9.1), need for sedation with prior imaging studies (p&lt;0.001), parental premonition of requiring anesthesia for successful treatment (p&lt;0.001), duration of treatment, primary language (p&lt;0.001), and use of total body irradiation (OR 3.1, 95% CI 1.1, 9.3). CONCLUSION Identification of pre-radiation risk factors allowed for better recognition of patients at risk for treatment non-compliance and for requiring daily sedation. Future studies should focus on implementing the algorithm prospectively in an effort to identify and direct early intervention with behavioral training and/or anxiolytics to minimize the need for sedation.


2021 ◽  
Vol 17 (2) ◽  
pp. 118-124
Author(s):  
Amirmehdi Sarvestani ◽  
Mohammad Almasian ◽  
Amirhossein Nafari

Background: The prevalence of fungal infections has been increasing in recent years. Cystic fibrosis (CF) is a genetic disorder that affects organs such as the intestines, liver, pancreas, and especially the lungs. Introduction: Fungal pathogens are becoming a challenge in CF. Advanced medical science is associated with longer life expectancy in some patient groups. Method: A review was conducted on studies found on online databases, including Google Scholar, PubMed, and Scopus. Internet-based searches were performed on these databases for cystic fibrosis, respiratory infections, and fungal infection profiling to identify all relevant studies published between 2010 and 2020. Result: Fungal pathogens most frequently isolated from the respiratory tract include the Aspergillus genus, the Candida genus, Scedosporium apiospermum, and the Rasamsonia genus. In cystic fibrosis, these organisms usually colonize the respiratory and intestinal tracts and cause hypersensitivity responses and invasive diseases. Conclusion: Fungus-patient interactions are complicated and depend on various factors. Moreover, the emergence of drug-resistant species is a serious health issue, and the development of new treatments is crucial.


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