Efficacy of liposomal amphotericin against febrile neutropenia in pediatric patients receiving prophylactic voriconazole

2020 ◽  
Author(s):  
Ryoji Kobayashi ◽  
Satoru Matsushima ◽  
Daiki Hori ◽  
Hirozumi Sano ◽  
Daisuke Suzuki ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Liposomal Amphotericin ◽  
Pediatric Patients

#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.

#31: Risk Factors Associated with Mortality due to Multidrug-Resistant Organisms in Pediatric Oncology Patients with Febrile Neutropenia

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S15-S16
Author(s):  
Miguel A Minero ◽  
Asia Castro ◽  
Martha Avilés-Robles
Keyword(s):  
Risk Factors ◽  
Septic Shock ◽  
Febrile Neutropenia ◽  
Pediatric Oncology ◽  
Pediatric Patients ◽  
Bloodstream Infections ◽  
Oncology Patients ◽  
Factors Associated ◽  
Patients With Cancer ◽  
The Impact

Abstract Background Infectious processes are frequent complications presented in pediatric patients with cancer. Currently, the indiscriminate use of antibiotics induces resistance to available treatments, creating the emergence of multi-drug-resistant organisms (MDROs). Due to the impact in morbidity and mortality secondary to MDRO infection, we aimed to identify risk factors associated with mortality in infections due to MDROs in pediatric patients with cancer. Methods Case–control study nested in a prospective cohort of pediatric oncology patients with febrile neutropenia (FN) at Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City from March 2015 to September 2017. MDRO was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories. Patients with FN episodes who died from an infection due to MDROs were defined as cases and patients with FN episodes of an infection due to MDROs who did not die were defined as controls. Mucositis, septic shock, PICU stay, and bacterial prophylaxis (Trimethoprim/Sulfamethoxazole) were compared between groups. Descriptive statistics was performed and Pearson χ 2 or Student’s t-test were used to compare risk factors between groups. Results A total of 929 FN episodes were documented, 44.4% episodes occurred in male patients, mean age was 7.9 years, with the population under 5 years being the most represented (68.2%). The most frequent diagnosis was acute lymphoblastic leukemia in 75% followed by rhabdomyosarcoma in 10.5% and acute myeloid leukemia in 9.6%. Prophylaxis (trimethoprim/sulfamethoxazole) was used in 86%, mucositis was present in 9.2% of episodes. 12.1% had septic shock and 4.7% were admitted to PICU. In 148 FN episodes (15.9%) a microorganism was identified, of these 50 (33.7%) were due to an MDROs. Urinary tract infection was the most frequent site (49%), followed by bloodstream infections (47%). K. pneumoniae was the most frequent MDRO in 22.8%, followed by E. coli in 19.2% and P. aeruginosa in 14%. Septic shock was presented in 26% of MDROs infections. Overall mortality was 1.94% and only 0.86% (8) were secondary to MDROs. Of patients with MDRO isolated mortality was 30% (15/50). Mortality associated with bloodstream infection due to MDROs was 25% compared with other source of MDROs infections (3%) (P = 0.01). Septic shock was present in 40% of patients with death due to MDROs infection (P = 0.001). Conclusions In our population of children with FN episodes who had an isolated microorganism, infection due to MDROs are high (33.7%) and MDROs infection-directed mortality was as high as 30%. Bloodstream infections and septic shock were risk factors associated with mortality due to MDROs.

scholarly journals The diagnostic pitfalls of mucormycosis

2020 ◽  
Vol 12 (1) ◽  
pp. e2020079
Author(s):  
Margherita Mauro ◽  
Giuliana Lo Cascio ◽  
Rita Balter ◽  
Ada Zaccaron ◽  
Elisa Bonetti ◽  
...  
Keyword(s):  
Risk Factor ◽  
Case Report ◽  
B Cell ◽  
Liposomal Amphotericin ◽  
Pediatric Patients ◽  
Intensive Chemotherapy ◽  
Aggressive Disease ◽  
Non Hodgkin Lymphoma ◽  
Lichtheimia Corymbifera ◽  
Diagnostic Pitfalls

  Background Invasive mucormycosis is a very aggressive fungal disease among immunocompromised pediatric patients caused by saprophytic fungi that belong to the order of the Mucorales. Case Report We describe a case of  of Lichtheimia corymbifera infection in a 15-year-old child with B-cell Non-Hodgkin Lymphoma (NHL) involving lung, kidney and thyroid that initially was diagnosed as probable aspergillosis delaying the effective therapy for mucormycosis. Conclusions This case showed that also intensive chemotherapy with rituximab may represent a risk factor for mucormycosis infection. Liposomal amphotericin B and surgery  remain  key tools  for a successful treatment of this aggressive 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.

Analysis of Hypokalemia as a Side Effect of Liposomal Amphotericin in Pediatric Patients

2018 ◽  
Vol 37 (5) ◽  
pp. 447-450 ◽  
Author(s):  
Ryoji Kobayashi ◽  
Dai Keino ◽  
Daiki Hori ◽  
Hirozumi Sano ◽  
Daisuke Suzuki ◽  
...  
Keyword(s):  
Side Effect ◽  
Liposomal Amphotericin ◽  
Pediatric Patients

Treatment experience with liposomal amphotericin B in pediatric patients with kala-azar

2015 ◽  
Vol 4 (3) ◽  
pp. 222-229
Author(s):  
Can Acıpayam ◽  
Gülnaz Çulha ◽  
Ali Altunay ◽  
Fazilet Akoğlu ◽  
Alkan Yeral ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Liposomal Amphotericin ◽  
Pediatric Patients ◽  
Liposomal Amphotericin B ◽  
Treatment Experience ◽  
Kala Azar

scholarly journals Meropenem versus piperacillin/tazobactam with or without immunoglobulin as second-line therapy for febrile neutropenia in pediatric patients

2018 ◽  
Vol 51 (4) ◽  
pp. 473-477 ◽  
Author(s):  
Ryoji Kobayashi ◽  
Daiki Hori ◽  
Hirozumi Sano ◽  
Daisuke Suzuki ◽  
Kenji Kishimoto ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Pediatric Patients ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

scholarly journals Population Pharmacokinetics of Liposomal Amphotericin B in Pediatric Patients with Malignant Diseases

2006 ◽  
Vol 50 (3) ◽  
pp. 935-942 ◽  
Author(s):  
Ying Hong ◽  
Peter J. Shaw ◽  
Christa E. Nath ◽  
Satya P. Yadav ◽  
Katherine R. Stephen ◽  
...  
Keyword(s):  
Body Weight ◽  
Amphotericin B ◽  
Pediatric Oncology ◽  
Liposomal Amphotericin ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Pediatric Patients ◽  
Liposomal Amphotericin B ◽  
Population Pharmacokinetic ◽  
Malignant Diseases

ABSTRACT A population pharmacokinetic model of liposomal amphotericin B (L-AmB) in pediatric patients with malignant diseases was developed and evaluated. Blood samples were collected from 39 pediatric oncology patients who received multiple doses of L-AmB with a dose range from 0.8 to 5.9 mg/kg of body weight/day. The patient cohort had an average age of 7 years (range, 0.2 to 17 years) and weighed an average of 28.8 ± 19.8 kg. Population pharmacokinetic analyses were performed with NONMEM software. Pharmacokinetic parameters, interindividual variability (IIV), between-occasion variability (BOV), and intraindividual variability were estimated. The influence of patient characteristics on the pharmacokinetics of L-AmB was explored. The final population pharmacokinetic model was evaluated by using a bootstrap sampling technique. The L-AmB plasma concentration-time data was described by a two-compartment pharmacokinetic model with zero-order input and first-order elimination. The population mean estimates of clearance (CL) and volume of distribution in the central compartment (V 1) were 0.44 liters/h and 3.12 liters, respectively, and exhibited IIV (CL, 10%) and significant BOV (CL, 46% and V 1, 56%). The covariate models were CL (liters/h) = 0.44 · e 0.0152 · (WT − 21 ) and V 1 (liters) = 3.12 · e 0.0241  ·  (WT  −  21), where WT is the patient's body weight (kg) centered on the study population cohort median of 21 kg. Model evaluation by the bootstrap procedure indicated that the full pharmacokinetic model was robust and parameter estimates were accurate. In conclusion, the pharmacokinetics of L-AmB in pediatric oncology patients were adequately described by the developed population model. The model has been evaluated and can be used in the design of rational dosing strategies for L-AmB antifungal therapy in this special population.

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