scholarly journals Diagnostic Capacity for Invasive Fungal Infections in the Greek Paediatric Haematology-Oncology Units: Report from the Infection Working Group of the Hellenic Society of Paediatric Haematology-Oncology

2021 ◽  
Vol 7 (5) ◽  
pp. 357
Author(s):  
Anthi-Marina Markantonatou ◽  
Athanasios Tragiannidis ◽  
Vasiliki Galani ◽  
Dimitrios Doganis ◽  
Kondilia Antoniadi ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Relevant Information ◽  
Turnaround Time ◽  
Invasive Fungal Infections ◽  
Therapeutic Drug ◽  
Sensitivity Testing ◽  
Paediatric Haematology ◽  
Clinical Mycology ◽  
Diagnostic Capacity ◽  
Hospitalised Patient

An audit based on a specific questionnaire was attempted, in order to investigate the mycology laboratory diagnostic capacity for invasive fungal diseases (IFDs) in Greek Paediatric Haematology-Oncology departments/units. The study provided the relevant information for the years 2019 and 2020 and included data from all units, concerning culture-based methods and direct microscopy, phenotypic and molecular identification, sensitivity testing, serology and molecular diagnosis, as well as therapeutic drug monitoring. The target was mostly to reveal the level of laboratory coverage for hospitalised paediatric patients, independently of the possibility of performing the tests in the host hospital, or otherwise to refer the specimens elsewhere. In total, the current study demonstrated that the most important facilities and services regarding the IFD diagnostics for paediatric haematology-oncology patients in Greece are available and relatively easily accessible, with a reasonable turnaround time. Acting as an initial registry for further improvements, the audit can serve as a valuable approach to the actual situation and future perspectives. A national clinical mycology network under the auspices of the relevant scientific societies will probably facilitate collaboration between all the departments (clinical and laboratory) involved in invasive fungal infections and provide an easier approach to any necessary test for any hospitalised patient.

Therapeutic Drug Monitoring of Voriconazole in the Management of Invasive Fungal Infections: A Critical Review

2015 ◽  
Vol 54 (12) ◽  
pp. 1223-1235 ◽  
Author(s):  
Hazem Elewa ◽  
Eman El-Mekaty ◽  
Ahmed El-Bardissy ◽  
Mary H. H. Ensom ◽  
Kyle John Wilby
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Critical Review ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Therapeutic Drug

scholarly journals Prophylaxis of Invasive Fungal Infections: A Review of the Use of Posaconazole

2009 ◽  
Vol 1 ◽  
pp. CMT.S1948
Author(s):  
Curtis D. Collins ◽  
Jeannina A. Smith ◽  
Daniel R. Kaul
Keyword(s):  
At Risk ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Case Reports ◽  
Case Series ◽  
Individual Case ◽  
Invasive Fungal Infections ◽  
Cost Of Care ◽  
Therapeutic Drug ◽  
Patients At Risk

Invasive fungal infections (IFIs) cause significant morbidity, mortality, and increased cost of care in patients with hematological malignancies, prolonged (i.e. >7-10 days) treatment induced neutropenia, and other disease states causing underlying immunosuppression. One strategy often used to combat the development of invasive infections is the use of antifungal agents as prophylaxis in at risk patients. Posaconazole is an oral triazole with a useful spectrum of activity against many fungal pathogens of concern in patients at risk for the development of IFIs. Posaconazole is only available in oral formulation and therapeutic drug monitoring may provide value due to variable absorption and serum concentrations. Clinical efficacy and pharmacoeconomic data have demonstrated the utility of posaconazole in the treatment of oropharyngeal candidiasis and for prophylaxis in patients at risk for development of IFIs. Several organizations or expert groups involved in developing guidelines for the management of IFIs recommend posaconazole anti-fungal prophylaxis in patients with AML or MDS and chemotherapy induced neutropenia or significant GVHD. In addition, nonrandomized studies (largely of salvage therapy) and case series suggest that posaconazole may be effective as treatment for invasive aspergillosis, zygomycosis, and coccidiomycosis. Further, small case series or individual case reports suggest activity against other less commonly encountered filamentous fungi and Histoplasma.

scholarly journals Antifungal Pipeline

2021 ◽  
Vol 11 ◽  
Author(s):  
Todd Patrick McCarty ◽  
Peter G. Pappas
Keyword(s):  
Antifungal Agents ◽  
Fungal Infections ◽  
Mechanisms Of Action ◽  
Invasive Fungal Infections ◽  
Fungal Diseases ◽  
Stages Of Development ◽  
The Past ◽  
Clinical Mycology ◽  
Dosing Regimens ◽  
Advanced Stages

In many ways, fungal diseases are forgotten or neglected. Given the significantly lower frequency compared to similar bacterial etiologies across the spectrum of infectious syndromes, it makes sense that anti-bacterial agents have seen the bulk of development in recent decades. The vast majority of new antifungal medications approved for use in the past 10 years have been new versions in the same class as existing agents. Clinical mycology is crying out for new mechanisms of action in the setting of rising resistance and emergence of new organisms. Fortunately, this trend appears to be reversing. There are numerous agents in advanced stages of development offering novel dosing regimens and mechanisms of action to combat these threats. Herein we review seven antifungal agents that we hope to see come to market in the coming years to aid physicians in the treatment of mucocutaneous and invasive fungal infections.

Posaconazole: An Oral Triazole with an Extended Spectrum of Activity

2008 ◽  
Vol 42 (10) ◽  
pp. 1429-1438 ◽  
Author(s):  
Erik J Rachwalski ◽  
Jeffrey T Wieczorkiewicz ◽  
Marc H Scheetz
Keyword(s):  
English Language ◽  
Fungal Infections ◽  
Data Extraction ◽  
Treatment Options ◽  
Drug Application ◽  
Invasive Fungal Infections ◽  
Therapeutic Drug ◽  
Hematopoietic Stem ◽  
Yeasts And Molds

Objective: To summarize the published clinical data on posaconazole, critically review the New Drug Application data submitted to the Food and Drug Administration, and provide information critical for evaluation and formulary positioning. Data Sources: Reported investigations were identified from MEDLINE (1966-June 30, 2008), bibliographies of manuscripts, www.clinicaltrials.gov , and www.fda.gov . Study Selection and Data Extraction: English-language articles were selected. AN available in vitro, animal, clinical, and human studies describing the pharmacology, pharmacokinetics, pharmacodynamics, efficacy, safety, and adverse events of posaconazole were reviewed. Data Synthesis: Posaconazole is an oral broad-spectrum triazole with activity against many yeasts and molds. Resistance to posaconazole has been reported, but has been rare to date. Posaconazole, in doses of 200 mg 3 limes daily, reduced breakthrough invasive fungal infections (OR 0.30; 95% CI 0.12 to 0.71) and aspergillosis incidence (OR 0.31; 95% CI 0.13 to 0.75) in patients receiving hematopoietic stem-cell transplants compared with those receiving fluconazole. Similarly, the same regimen of posaconazole reduced invasive fungal infections (95% CI -9.7 to -2.5) and aspergillosis (CI not reported, p < 0.001) when compared with fluconazole and itraconazole in neutropenic patients. Posaconazole is non-inferior to fluconazole for treatment of oropharyngeal candidiasis (95% CI -6.6 to 5.0), but necessity for this indication remains unclear, as many other treatment options exist. Smaller investigations have analyzed use of posaconazole for patients requiring salvage or alternative treatment for zygomycosis, fusarbsis, cryptococcal meningitis, coccidioidomycosis, and histoplasmosis. Studies are needed to clarify efficacy for such expanded use, and therapeutic drug monitoring may improve outcomes. The most common adverse effects associated with the use of posaconazole include headache, fever, nausea, vomiting, and diarrhea. Conclusions: Posaconazole appears to be a valuable and promising addition to the antifungal armamentarium for prophylaxis and treatment of various fungal processes. At this time, posaconazole should probably be reserved for prophylaxis in patients at high risk for invasive fungal infection, as salvage therapy in refractory or resistant infections, or for patients with intolerance to other therapies.

scholarly journals Management of Invasive Fungal Infections in Adult Patients with Hematological Malignancies in Greece during the Financial Crisis: Challenges and Recommendations

2018 ◽  
Vol 4 (3) ◽  
pp. 94 ◽  
Author(s):  
Nikolaos V. Sipsas ◽  
Maria N. Pagoni ◽  
Diamantis P. Kofteridis ◽  
Joseph Meletiadis ◽  
Georgia Vrioni ◽  
...  
Keyword(s):  
Financial Crisis ◽  
Hematological Malignancies ◽  
Fungal Infections ◽  
Patient Characteristics ◽  
Invasive Fungal Infections ◽  
Therapeutic Drug ◽  
Treatment Practices ◽  
Timely Fashion ◽  
Greek Hospitals ◽  
Construction Works

There are concerns that the financial crisis in Greece negatively affected the management of invasive fungal infections (IFIs) among patients with hematological malignancies (HM). A working group (WG) was formed to explore the situation and make recommendations. A questionnaire was created and distributed to physicians caring for patients with HM, to gather information in a standardized manner on prescribing physicians, patient characteristics, availability of diagnostics, antifungal treatment practices and the conditions and particularities of Greek hospitals. A total of 141 physicians from 36 hematology units and laboratories located in 26 Greek hospitals participated. Regarding hospitalization conditions, only 56% reported that their patients were treated in isolated single or double bed rooms, 22% reported availability of HEPA filters, 47% reported construction works in progress, and an alarming 18% reported the presence of birds on open windows. Regarding diagnosis, only 31% reported availability of biomarkers for diagnosis of IFIs, 76% reported that CT scans were performed in a timely fashion, 42% reported prompt availability of broncho-alveolar lavage, and only 6% availability of therapeutic drug monitoring. Of concern, 26% of the responders reported non-availability of some antifungals. In conclusion, significant challenges exist for the optimal management of IFIs in patients with HM in Greece.

scholarly journals Updates in Laboratory Diagnostics for Invasive Fungal Infections

2020 ◽  
Vol 58 (6) ◽  
Author(s):  
David Terrero-Salcedo ◽  
Margaret V. Powers-Fletcher
Keyword(s):  
Fungal Infections ◽  
Diagnostic Testing ◽  
Diagnostic Error ◽  
Invasive Fungal Infections ◽  
Innovative Technology ◽  
Laboratory Diagnostics ◽  
Fungal Culture ◽  
Clinical Mycology ◽  
Patient Health ◽  
Identification Techniques

ABSTRACT Appropriate diagnosis of invasive fungal infections (IFIs) is critical due to the high rates of morbidity and mortality, as well as the substantial economic burden, associated with the management of these diseases. The recognition of IFI and differentiation from other infections with similar clinical presentations can be challenging, which can lead to diagnostic error that not only has an impact on individual patient health outcomes but also on antimicrobial drug usage and the growing threat of antimicrobial resistance in bacteria. Therefore, there is a significant need for improved stewardship related to diagnostic testing for and treatment of IFIs. The purpose of this review is to highlight recent advances related to current fungal diagnostics, as well as explore some of the most innovative technology that has emerged with the potential to shift the paradigm of clinical mycology. In general, this review will discuss research related to enhanced fungal culture utilization and identification techniques, expanded applications of fungal antigen testing, and recently developed molecular assays and other novel nonculture fungal diagnostic approaches. Specifically, the application of mass spectrometry, novel glycobiomarker detection, and detection of fungal-specific volatile organic compounds will be reviewed, along with other key updates, to provide the reader with an updated review that extends beyond the basics of IFI laboratory diagnostics. Where appropriate, the reader will be directed to more comprehensive reviews of certain aspects of clinical mycology laboratory testing to provide a broader context for the critical consideration of these updates.

scholarly journals 1127. Utilization of Combination Anti-fungal Therapy in Hospitalized Children and Adverse Events

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S401-S401
Author(s):  
Tonya Scardina ◽  
Zacharoula Oikonomopoulou ◽  
Shan Sun ◽  
Sameer Patel
Keyword(s):  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Normal Liver ◽  
Invasive Fungal Infections ◽  
Primary Site ◽  
Therapeutic Drug ◽  
Hospitalized Children ◽  
Antifungal Stewardship ◽  
European Organization ◽  
Anti Fungal

Abstract Background Combination antifungal therapy (CAF) is often prescribed to treat invasive fungal infections, despite equivocal data showing benefit. We evaluated number of CAF for treatment of proven, probable and possible invasive fungal infection (IFI) in hospitalized children, associated adverse effects (AE), and use of therapeutic drug monitoring (TDM). Methods Medical charts of patients ≤ 18 years old that received CAF for ≥72 hours with normal liver function test between 1/1/13 through December 31/18 were reviewed. Patients could be included for multiple episodes of CAF. Data included primary site of IFI, host risk factors, demonstration of fungal elements in tissue/sterile sites, clinical and mycological criteria for IFI (defined by European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group), CAF regimen, incidence of TDM, and AE. Results Overall, 73 episodes of IFI were reviewed [unique patients (n) =60]. The median age was 10 years. Majority (61.6%) of patients were diagnosed with a hematological malignancy (n = 20 acute lymphoblastic leukemia, n = 12 acute myeloid leukemia, n = 5 aplastic anemia). A number of proven, possible, probable IFI were 36, 27 and 20, respectively (Table 1). Most frequent organism isolated in proven IFI was Aspergillus fumigatus (episodes=5, n = 4). Most common primary site of IFI was pulmonary (episodes=32, n = 27). Median days of CAF was 6.8 (range: 3–170). Sixty-six episodes included treatment with a triazole-containing regimen (90%). TDM was conducted in 51 (77%) episodes of triazole-containing regimens. AE were reported in 14 episodes (n = 10) (infusion-related reactions and nephrotoxicity reported in 4 episodes each, electrolyte abnormalities and skin reaction reported in 2 episodes each, and liver dysfunction and hypersensitivity reported in 1 episode each). Conclusion Patients diagnosed with proven or probable IFI received a longer duration of CAF in comparison to possible IFI. Voriconazole was frequently prescribed in combination with either micafungin or liposomal amphotericin B for IFI. Antifungal stewardship opportunities exist to improve TDM and reduce the incidence of AE when prescribing CAF. Disclosures All authors: No reported disclosures

scholarly journals 1733. Voriconazole Prophylaxis Following Allogeneic Hematopoietic Stem Cell Transplant: How Much Is Enough, Are Low Voriconazole Levels Associated With Opportunistic Infections, and What Are the Reasons for Discontinuation?

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S635-S635
Author(s):  
Giorgos Hadjivassiliou ◽  
Claire Rummage ◽  
Craig Hoesley ◽  
Matthew L Brown
Keyword(s):  
Stem Cell ◽  
Therapeutic Drug Monitoring ◽  
Hematopoietic Stem Cell ◽  
Drug Monitoring ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Therapeutic Drug ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Subtherapeutic Level

Abstract Background Patients who undergo allogeneic hematopoietic stem cell transplantation (alloHSCT) are at increased risk for invasive fungal infections with associated high morbidity and mortality that necessitates the use of prophylactic antifungals. Voriconazole is commonly used for prophylaxis, but there are no recommendations for therapeutic drug monitoring. The purpose of this study was to characterize voriconazole therapeutic drug monitoring and associated outcomes in this patient population. Methods AlloHSCT patients receiving voriconazole prophylaxis at the University of Alabama at Birmingham Hospital between March 2015 and March 2018 were included in the analysis. Serum voriconazole levels (SVL) were evaluated to determine what percentage of patients achieved prophylactic or therapeutic concentrations. Incidence of invasive fungal infections (IFI) and voriconazole discontinuation was also assessed. Results Voriconazole prophylaxis was used in 151 of 162 alloHSCT patients, and 120 patients (79%) had SVL drawn correctly (≥4 days after initiation of course). We found that 35 (29%) patients achieved a subtherapeutic level (<0.5 μg/mL), 17 (14%) prophylactic level (0.5 to 1 μg/mL), 68 (57%) therapeutic level (1 to 5.5 μg/mL), and no patients achieved a supratherapeutic level (level ≥5.5 μg/mL). Voriconazole prophylaxis was discontinued early in 60 of 151 patients. Most common etiologies for discontinuation included liver function test abnormalities (44%) and encephalopathy (21%). The average SVL was 1.2 μg/mL in those requiring discontinuation. Four patients (3%) developed an IFI while receiving prophylactic voriconazole, of which only 1 had subtherapeutic level. Conclusion Even though approximately one-third of patients achieved a subtherapeutic SVL, there was no correlation with breakthrough IFI. There was also no linear correlation between SVL and risk of adverse effects requiring discontinuation. Our observational data do not support a need for therapeutic drug monitoring in alloHSCT patients receiving prophylactic voriconazole. Disclosures All authors: No reported disclosures.

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