isavuconazole and Neoplasms

Invasive fungal diseases (IFD) are life-threatening and demand timely and appropriate treatment. Research showed that isavuconazole treatment positively affects clinical outcome and length of hospital stay (LOS).. The aim of this study was to assess the hospital costs of patients diagnosed with IFD and treated with isavuconazole using real-world data from a German cancer centre.. Data and LOS collected from Jan-2016 to Jun-2021 at Department I of Internal Medicine, University Hospital Cologne were retrieved. Case-related resources consumed during the hospital stay across isavuconazole routes of administration (oral, parenteral, and mixed administration) were identified, quantified, valued and compared via a cost analysis that adopted the healthcare payer perspective.. In total, 101 cases with isavuconazole treatment were identified (oral: n = 22, 21.8%; parenteral: n = 59, 58.4%; mixed: n = 20, 19.8%). Median total LOS was greater in the mixed group (46.5 days; p = .009). Median ICU LOS and ventilation duration were both longest in the parenteral-only group (16 days, p = .008; 224 h, p = .003). Invasive aspergillosis was the most frequent isavuconazole indication (n = 86, 85.2%). Average hospital costs were highest in the mixed group (€ 101,226). The median overall costs of cases treated with isavuconazole was € 52,050.. Treating IFD is resource intensive, often requires intensive care and implies high rates of in-hospital mortality. Our study emphasises the high hospital treatment costs and thus the need for reimbursement systems to enable live-saving costly treatments.

Topics: Antifungal Agents; Aspergillosis; Humans; Invasive Fungal Infections; Neoplasms; Nitriles; Triazoles

To study the isavuconazole pharmacokinetics in a real-life paediatric cohort and confirm whether the isavuconazole exposures are within the adult exposure range. Furthermore, we are the first to describe unbound isavuconazole pharmacokinetics.. In this prospective, observational study, the isavuconazole dosing regimen was as follows (IV/oral/nasogastric tube): 5.4 mg/kg isavuconazole (maximum 200 mg/dose) three times daily on Days 1 and 2, followed by 5.4 mg/kg isavuconazole (maximum 200 mg/dose) once daily. At least one pharmacokinetic curve was assessed. Non-linear mixed effects modelling was used for analysis. Monte Carlo simulations were performed with the above mentioned maintenance dose for IV administrations and a weight band dosing regimen for oral/nasogastric tube administrations: I) <18 kg (100 mg daily); II) 18-37 kg (150 mg daily); III)>37 kg (200 mg daily).. Seventeen paediatric patients with a median age of 9 years (range 1-17) and median weight of 26.0 kg (range 8.4-78.5) were evaluated. A two-compartment model describing linear pharmacokinetics of the unbound concentrations and saturable protein binding fitted the isavuconazole concentrations best. The absolute bioavailability of isavuconazole was 41.0% (95% CI: 32.4%-50.8%). The median (IQR) simulated exposures (AUC0-24h, SS) of the total isavuconazole concentrations after IV and oral/nasogastric tube administration were 87.7 mg·h/L (70.5-105.1) and 50.3 mg·h/L (39.0-62.4), respectively. The unbound isavuconazole fraction (unbound/total) ranged from 0.5% to 2.3%.. This study revealed low bioavailability after nasogastric tube administration with opened capsules. Isavuconazole exposures were in the expected range following IV administration. Total and unbound isavuconazole pharmacokinetics were reported with a 5-fold range in the unbound fraction.

Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Infant; Neoplasms; Nitriles; Prospective Studies; Pyridines

Limited evidence concerning optimal azole dosing regimens currently exists for antifungal prophylaxis in hemato-oncological pediatric patients.. Hemato-oncological children receiving intravenous or oral isavuconazole or voriconazole for primary antifungal prophylaxis at IRCCS Azienda Ospedaliero-Universitaria of Bologna during November 2020 to October 2021 and undergoing CPA programs based on real-time therapeutic drug monitoring (TDM) were retrospectively analyzed. CPAs for isavuconazole and voriconazole and the number of dosage adjustments were collected. Normalized trough concentrations [(C min )/dose/kg] were calculated for both drugs at each TDM assessment, and the coefficient of variation was determined. The efficacy and safety of the drugs were evaluated.. Sixteen hemato-oncological pediatric patients received azole prophylaxis (mean age and weight: 9.1 ± 4.9 years and 32.6 ± 16.0 kg; 6 isavuconazole and 10 voriconazole). Sixty and 89 CPAs were delivered as isavuconazole and voriconazole, respectively. Dosage adjustments were needed in 3.3% of cases for isavuconazole and 53.9% of cases for voriconazole ( P < 0.001). At first TDM, achievement of the desired target during standard dosing regimens was higher for isavuconazole (83.3%) than for voriconazole (10.0%; P = 0.008). Dispersion of normalized concentrations was higher for voriconazole (CV = 139.1% vs. CV = 79.4%). Elevation of ALT and aspartate aminotransferase levels between baseline and the third month was higher in patients receiving voriconazole (median, 28 vs. 90 U/L; P = 0.038, and 19 vs. 65.5 U/L; P = 0.002).. Our findings suggest that there is limited variability in isavuconazole exposure in hemato-oncological pediatric patients receiving azole prophylaxis , resulting in a low need for CPA-guided dosage adjustments.

Topics: Antifungal Agents; Azoles; Child; Humans; Invasive Fungal Infections; Neoplasms; Nitriles; Pyridines; Retrospective Studies; Triazoles; Voriconazole

Opportunistic infections due to Candida species occur frequently in intensive care settings. We investigated the prevalence of Candida species among 65 clinical specimens obtained from 200 cancer patients by phenotypic and molecular (ITS sequencing and AFLP) methods. Among the 65 yeast isolates, Candida albicans was the most commonly isolated species (n = 34, 52.3%), whereas other Candida species comprised 47.7% (n = 31) and consisted of Candida glabrata (n = 14, 21.5%), Candida tropicalis (n = 5, 7.7%) and uncommon Candida species (n = 12, 18.5%) such as Candida pelliculosa (n = 3, 4.6%), Pichia kudriavzevii (= Candida krusei, n = 2, 3.1%), Candida orthopsilosis (n = 2, 3.1%), Candida parapsilosis (n = 1, 1.5%), Candida infanticola (n = 2, 3.1%), Candida spencermartinsiae (n = 1, 1.5%), and Kluyveromyces marxianus (=Candida kefyr, n = 1, 1.5%). Candida infanticola and Candida spencermartinsiae were recovered from oral lesions of cancer patients. Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) easily confirmed these isolates as less common Candida isolates (4.6%). The in vitro antifungal susceptibilities of C. spencermartinsiae and the two strains of C. infanticola were determined according to CLSI guidelines (M27-A3). MIC results among these isolates showed they were susceptible to isavuconazole, posaconazole and voriconazole, however, fluconazole and caspofungin had high MIC values. These Candida species that may occur more commonly in infections remain unnoticed using commonly used phenotypical methods in routine microbiology laboratories. MALDI-TOF MS proved to be a more fast and robust diagnostic technique for identification of the yeasts isolated from different clinical specimens of cancer patients.

Topics: Adolescent; Antifungal Agents; Candida; Candidiasis; Caspofungin; Child, Preschool; Echinocandins; Fluconazole; Humans; Kluyveromyces; Lipopeptides; Male; Microbial Sensitivity Tests; Middle Aged; Neoplasms; Nitriles; Opportunistic Infections; Pichia; Pyridines; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Triazoles; Voriconazole