scholarly journals Evaluation of Posaconazole Serum Concentrations from Delayed-Release Tablets in Patients at High Risk for Fungal Infections

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Alan Chin ◽  
Steven A. Pergam ◽  
David N. Fredricks ◽  
Andrew N. Hoofnagle ◽  
Kelsey K. Baker ◽  
...  
Keyword(s):  
High Risk ◽  
Fungal Infections ◽  
Medical Condition ◽  
Solid Organ Transplantation ◽  
Serum Levels ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
High Risk Patients ◽  
Delayed Release ◽  
Risk Patients

ABSTRACT The purpose of our study was to determine the frequency of patients who achieved a therapeutic drug level after receiving posaconazole (PCZ) delayed-release tablets (DRT) for prophylaxis or treatment of invasive fungal infections (IFIs) and to examine the effect of demographic traits and treatment characteristics on PCZ serum levels. A retrospective single-center study was conducted on high-risk inpatients at the University of Washington Medical Center (UWMC) that had received PCZ and obtained PCZ serum levels for either treatment or prophylaxis between 1 August 2014 and 31 August 2015. High-risk patients were defined as those undergoing chemotherapy for a primary hematologic malignancy and those undergoing hematopoietic cell transplantation (HCT) or solid organ transplantation. Serum trough concentrations of ≥700 μg/liter and ≥1,000 μg/liter were considered appropriate for prophylaxis and treatment, respectively. The most frequent underlying medical condition was a hematological malignancy (43/53, 81%). Twenty-six of 53 patients (49%) received PCZ for prophylaxis; the rest received PCZ for treatment. A total of 37/53 (70%) patients had PCZ serum levels of ≥700 μg/liter regardless of indication, including 22/26 (85%) that received PCZ for prophylaxis. Of the patients that received PCZ for treatment, only 12/27 (44%) had PCZ serum levels of ≥1,000 μg/liter. The odds of having therapeutic PCZ serum levels were not statistically different in patients with a weight of ≥90 kg, a diarrhea grade of ≥2, a mucositis grade of ≥2, or poor dietary intake. However, the odds of having therapeutic PCZ serum levels was 5.85 times higher in patients without graft-versus-host disease (GVHD) treatment than in those with GVHD treatment. Four patients on prophylaxis (15%) developed breakthrough IFIs, one of which had a subtherapeutic level. We concluded that the use of PCZ DRT provided adequate concentrations in only 70% of our patients and that recommended dosing may lead to insufficient levels in patients treated for IFIs. Lower concentrations noted among high-risk patients with GVHD suggest a need for prospective studies evaluating therapeutic drug monitoring and/or dose adjustments among these patients.

Neuroblastoma: An Updated Review on Biology and Treatment

2020 ◽  
Vol 20 (13) ◽  
pp. 1014-1022 ◽  
Author(s):  
Suresh Mallepalli ◽  
Manoj Kumar Gupta ◽  
Ramakrishna Vadde
Keyword(s):  
Survival Rate ◽  
High Risk ◽  
Molecular Mechanisms ◽  
Definitive Treatment ◽  
Therapeutic Drug ◽  
Mycn Amplification ◽  
Dependent Manner ◽  
High Risk Patients ◽  
Treatment And Prevention ◽  
Risk Patients

Background: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human. Objectives: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans. Conclusions: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery &radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans.

Evaluation of posaconazole plasma concentrations achieved with the delayed‐release tablets in Korean high‐risk patients with haematologic malignancy

Mycoses ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Hyojin Chae ◽  
Sung‐Yeon Cho ◽  
Yunmi Yi ◽  
Jeong Joong Lee ◽  
Kyoungho Cha ◽  
...  
Keyword(s):  
High Risk ◽  
Plasma Concentrations ◽  
High Risk Patients ◽  
Delayed Release ◽  
Risk Patients

scholarly journals 1701. Differences in Diagnostic Performance of β-d-Glucan Testing in Patients with Varying Degrees of Susceptibility to Invasive Fungal Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S623-S623
Author(s):  
Eliel Nham ◽  
Si-Ho Kim ◽  
Hyunjoo Lee ◽  
Jae-Hoon Ko ◽  
Kyungmin Huh ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Diagnostic Performance ◽  
Fungal Infections ◽  
Pneumocystis Pneumonia ◽  
Host Factors ◽  
European Organization ◽  
High Risk Patients ◽  
Risk Patients ◽  
Group A

Abstract Background Usefulness of β-d-glucan (BDG) testing in high-risk patients for invasive fungal infection (IFI) diagnosis has been well demonstrated. However, data on its usefulness in patients without risk factors are limited. We evaluated differences in the diagnostic performance of BDG testing in patients with varying degrees of susceptibility to IFI. Methods From April 2017 to May 2018, all consecutive patients (≥18year-old) who were performed BDG testing (Beijing Gold Mountainriver Tech) were enrolled. Patients were classified into three groups: Group A for patients with host factors defined by 2008 European Organization for Research and Treatment of Cancer-Mycoses Study Group diagnostic (EORTC-MSG) criteria, Group B for patients with malignancy receiving recent chemotherapy within 1 month without host factors, and Group C for others. Cases of proven and probable IFI defined by EORTC-MSG criteria, Pneumocystis pneumonia and all fungemia were considered as true IFIs. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) were calculated with a cut-off value for positivity ≥80 pg/mL. Results Among 473 eligible patients, 190, 142, and 141 patients were classified into group A, B, and C, respectively. Rates of true IFI were significantly different in each group (57/190, 19/142, and 10/141 in each group, P < 0.001). Sensitivities were 0.83, 0.68, and 0.70 and specificities were 0.62, 0.59, and 0.63 in group A, B, and C, respectively. PPVs were considerably different among three groups (PPV for 0.48, 0.20, and 0.12; NPV for 0.89, 0.92 and 0.97 in each group, respectively). Conclusion The BDG test is a useful assay for IFI diagnosis; however, the clinical interpretation should be different by patient risks. Whereas BDG testing could be considered as a tool for predicting IFI in high-risk patients, it only could be a tool for excluding IFI in patient without risk factors. Disclosures All authors: No reported disclosures.

Is Antifungal Prophylaxis Useful In Stem Cell Transplantation (SCT) During Hospitalization?.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4541-4541
Author(s):  
Giuseppe Irrera ◽  
Messina Giuseppe ◽  
Giuseppe Console ◽  
Massimo Martino ◽  
Cuzzola Maria ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Mucosal Damage ◽  
Invasive Disease ◽  
Secondary Prophylaxis ◽  
Antifungal Prophylaxis ◽  
Antifungal Drugs ◽  
High Risk Patients ◽  
Risk Patients

Abstract Abstract 4541 Introduction: Limited data demonstrate to what extent preventing fungal exposures is effective in preventing infection and disease. Further studies are needed to determine the optimal duration of fluconazole prophylaxis in allogeneic recipients to prevent invasive disease with fluconazole-susceptible Candida species during neutropenia. Oral, nonabsorbable antifungal drugs might reduce superficial colonization and control local mucosal candidiasis, but have not been demonstrated to reduce invasive candidiasis. Anti-fungal prophylaxis is recommended in a subpopulation of autologous recipients with underlying hematologic malignancies with prolonged neutropenia and mucosal damage. Methods: This is a retrospective study of 1007 SCT performed in our center between 1992 and 2009 in 809 consecutive patients, irrespective of diagnosis. HEPA filter and environmental monitoring (air, water, surfaces) are attributes of our transplant center. Results: The main characteristics of the patients are reported in Table 1. Systemic prophylaxis was used according to the guidelines (Table 2): fluconazole in the nineties, then itraconazole and from 2004 was either abolished or substituted with non-adsorbable prophylaxis in transplants with standard risk. Secondary prophylaxis was prescribed for high risk patients (with infectious fungal history, suggestive iconography, positive fungal biomarker). In 17 years our Center has never been colonized by mould. Only 3 probable aspergillosis infections and 4 proven fungal infections (fusarium, mucor and 2 aspergillosis) were diagnosed, all in allogeneic patients (2 haplotipical, 1 singenic, 1 sibiling, 1 MUD and 2 mismatched), resulting in death in all cases. No infection was documented in autologous setting, while the infection rate in allogenic setting was 3.6% with an incidence rate of 1.1 infection per 10000 transplants/year. These results are significantly lower than published reports. Conclusion: Systemic antifungal prophylaxis should not be performed in autologous SCT patients. The abuse of systemic prophylaxis targeting yeasts has influenced the change of epidemiology in the transplant setting with prevalence of mould infections. The identification of high risk patients is useful to select patients for systemic antifungal or secondary prophylaxis to reducing overtreatment, incidence of resistant strains and costs. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Phase 1b Study of New Posaconazole Tablet for Prevention of Invasive Fungal Infections in High-Risk Patients with Neutropenia

2014 ◽  
Vol 58 (10) ◽  
pp. 5758-5765 ◽  
Author(s):  
Rafael F. Duarte ◽  
Javier López-Jiménez ◽  
Oliver A. Cornely ◽  
Michel Laverdiere ◽  
David Helfgott ◽  
...  
Keyword(s):  
High Risk ◽  
Fungal Infections ◽  
Average Concentration ◽  
Myelogenous Leukemia ◽  
Time Curve ◽  
Once Daily ◽  
High Risk Patients ◽  
Exposure Target ◽  
Risk Patients ◽  
Neutropenic Patients

ABSTRACTPosaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n= 20) and 300 mg posaconazole once daily (n= 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered atClinicalTrials.govunder registration no. NCT01777763.)

Mortality, length of hospitalization, and costs associated with invasive fungal infections in high-risk patients

2009 ◽  
Vol 66 (19) ◽  
pp. 1711-1717 ◽  
Author(s):  
Joseph Menzin ◽  
Juliana L. Meyers ◽  
Mark Friedman ◽  
John R. Perfect ◽  
Amelia A. Langston ◽  
...  
Keyword(s):  
High Risk ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
High Risk Patients ◽  
Risk Patients ◽  
Length Of Hospitalization

scholarly journals Serum Concentrations of Posaconazole (PCZ) With Delayed-Release Tablets (DRT) in High-Risk Patients

2016 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
Alan Chin ◽  
Steven A. Pergam ◽  
David N Fredricks ◽  
Rupali Jain
Keyword(s):  
High Risk ◽  
Serum Concentrations ◽  
High Risk Patients ◽  
Delayed Release ◽  
Risk Patients

scholarly journals Prophylaxis and treatment of invasive fungal infections in hematological patients

2012 ◽  
Vol 3 (1S) ◽  
pp. 27
Author(s):  
Alessandro Busca ◽  
Anna Candoni ◽  
Livio Pagano ◽  
Francesco Scaglione ◽  
Claudio Viscoli
Keyword(s):  
High Risk ◽  
Fungal Infections ◽  
Empiric Therapy ◽  
Antifungal Prophylaxis ◽  
Antifungal Drugs ◽  
Remission Induction ◽  
Therapeutic Drug ◽  
Level Of Evidence ◽  
Dose Concentration ◽  
Risk Patients

The evidence from the literature strongly support antifungal prophylaxis in high risk haematological patients, such as patients with AML during remission induction chemotherapy and alloHSCT patients. Current antifungal prophylaxis guidelines for high risk patients recommend azoles (fluconazole, posaconazole, voriconazole) and echinocandins (micafungin) with the strongest level of evidence. In terms of treatment, the choice between empiric therapy (or fever driven) and pre-emptive therapy (or diagnostic driven) is still debated. Not a single therapeutic strategy is appropriate in every patients, in particular empirical antifungal therapy may be recommended in patients at very high risk, while a pre-emptive approach may be advised for those at standard risk. In order to exploit the synergistic and/or additive effect of two antifungal drugs it’s possible to combine two agents that work with different mechanisms of action (e.g. echinocandins + azoles or polyenes). Once the treatment has been initiated we should consider the therapeutic drug monitoring (TDM) of the drugs, especially when the pharmacokinetic variability is high and the dose-concentration effect relationships is not predictable (e.g. for itraconazole, voriconazole and posaconazole).

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