Important Infections Due To Molds

2018 ◽  
Author(s):  
Timothy Ando
Keyword(s):  
Invasive Aspergillosis ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Antibody Therapy ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Intravenous Route ◽  
Dematiaceous Fungi ◽  
Liver Function Testing

Mold-based fungal infections have become increasingly important over several decades, paradoxically because advances in medical practice have allowed patients with chronic medical conditions to live longer and have lives that are more productive. Allergic bronchopulmonary aspergillosis can affect those individuals with an atopic predisposition. Use of direct antimold antifungal agents can decrease the number of steroid treatment courses and monoclonal antibody therapy used in these patients. Pulmonary invasive aspergillosis remains the most important opportunistic mold infection among immunocompromised patients. Surrogate markers of diagnosis can include β-d-glucan or Aspergillus galactomannan antigen testing, although the specificity of both tests is not robust. There are three general classes of antifungal agents in use, with less nephrotoxic options. With safer therapeutic options, empirical treatment occurs with tremendous frequency among otherwise immunosuppressed individuals. Thus, clinicians will need to maintain a high suspicion for mold infections that can be resistant to a previously used antifungal therapy. Attention to liver function testing during long-term use of these advanced-generation azole antifungal agents, and at times therapeutic drug monitoring with blood levels, will be needed. The echinocandin class of antifungal agents does not have hepatic or renal toxicity in general, but these agents need to be administered via an intravenous route. With routine use of agents that have activity against aspergillosis, fusariosis, mucormycosis, or other mold infections become evident for a minority of at-risk patients. This review contains 5 figures, 3 tables and 90 references Key words: allergic bronchopulmonary aspergillosis, dematiaceous fungi, Exserohilum, fusariosis, invasive aspergillosis, mucormycosis, Scedosporium

24 Comparison of the tolerability of posaconazole versus voriconazole in children with cystic fibrosis

2018 ◽  
Vol 103 (2) ◽  
pp. e2.27-e2 ◽  
Author(s):  
Sian Bentley ◽  
Sukeshi Makhecha ◽  
Siobhan Carr ◽  
Ian Balfour-Lynn ◽  
Jane Davies
Keyword(s):  
Cystic Fibrosis ◽  
Adverse Effects ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Antifungal Prophylaxis ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
List Type ◽  
Retrospective Case ◽  
Clin Microbiol Infect ◽  
Hematopoietic Stem

BackgroundTriazole antifungals (itraconazole and voriconazole), are commonly used for treating isolates of Aspergillus, or in combination with corticosteroids for the empiric treatment of Allergic Bronchopulmonary Aspergillosis (ABPA) in children with cystic fibrosis (CF). Posaconazole is a newer triazole that is as effective, but better tolerated than voriconazole and itraconazole in immunocompromised patients1 though there is no published use in CF and it is not licensed in children<18 years old. It is used as a 3rd line agent for Aspergillus or ABPA in our institution.AimOur aim was to evaluate why posaconazole was needed in some children, and to assess its tolerability. Given the difficulty in reaching therapeutic drug levels of triazoles in children with CF2 we also reviewed posaconazole blood levels.MethodA retrospective case note review of all children with CF who had received voriconazole or posaconazole from April 2014 to May 2015 in a tertiary paediatric CF centre with a clinic population of 350 children. Children were identified from pharmacy records and clinical data was collected from case notes and computerised laboratory records. We compared reported adverse effects for both drugs, and for the posaconazole group documented reason for use and blood levels (therapeutic >0.7 mg/L).ResultsVoriconazole was used in 10 children with a median age of 13.5 years (range 12–16), for median 8 weeks. Adverse effects were experienced in 5/10 (50%) of children (photosensitivity – 4; hallucinations and nausea – 1), and 2 children had raised liver functions tests (LFTs). Posaconazole was used in 7 children with a median age of 14 years (range 13–16) for median 37 weeks. No adverse effects were reported but LFTs were raised in 1 child. Posaconazole was commenced in 6/7 (85%) children due to severe photosensitivity with voriconazole. Of these, posaconazole was indicated for concurrent Scedosporium isolates in 2 children, and therapeutic failure with itraconazole in 4 children. Posaconazole levels were consistently therapeutic in 5/7 (71%) children (range 0.7–2.47 mg/L). Levels in 1 child fell to <0.2 mg/L following the introduction of an interacting drug (rifampicin), and a level of 2.47 mg/L was associated with raised LFTs in another, resulting in discontinuation of posaconazole.ConclusionIn this small cohort, posaconazole was better tolerated than voriconazole for the treatment of Aspergillus or ABPA in children with CF, due mainly to the lack of photosensitivity associated with its use. Posaconazole levels attained from our patients indicate that therapeutic levels can be readily obtained in this patient population. Larger studies are needed to support these conclusions.ReferencesDoring M, Blume O, Haufe S, et al. Comparison of itraconazole, voriconazole, and posaconazole as oral antifungal prophylaxis in paediatric patients following allogeneic hematopoietic stem cell transplantation. Eur J Clin Microbiol Infect Dis2014;33(4):629–38.Bentley S, Gupta A, Balfour-Lynn IM. Subtherapeutic itraconazole and voriconazole levels in children with cystic fibrosis. J Cyst Fibros2013;12:418–9.

scholarly journals Exposure-Response Relationships for Isavuconazole in Patients with Invasive Aspergillosis and Other Filamentous Fungi

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Amit V. Desai ◽  
Laura L. Kovanda ◽  
William W. Hope ◽  
David Andes ◽  
Johan W. Mouton ◽  
...  
Keyword(s):  
Steady State ◽  
Invasive Aspergillosis ◽  
Filamentous Fungi ◽  
Aspartate Aminotransferase ◽  
Drug Exposure ◽  
Fungal Infections ◽  
Plasma Concentrations ◽  
Water Soluble ◽  
Therapeutic Drug ◽  
Exposure Response

ABSTRACT Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent for the treatment of invasive fungal infections. The purpose of this analysis was to characterize the isavuconazole exposure-response relationship for measures of efficacy and safety in patients with invasive aspergillosis and infections by other filamentous fungi from the SECURE clinical trial. Two hundred thirty-one patients who received the clinical dosing regimen and had exposure parameters were included in the analysis. The primary drug exposure parameters included were predicted trough steady-state plasma concentrations, predicted trough concentrations after 7 and 14 days of drug administration, and area under the curve estimated at steady state (AUCss). The exposure parameters were analyzed against efficacy endpoints that included all-cause mortality through day 42 in the intent-to-treat (ITT) and modified ITT populations, data review committee (DRC)-adjudicated overall response at end of treatment (EOT), and DRC-adjudicated clinical response at EOT. The safety endpoints analyzed were elevated or abnormal alanine aminotransferase, increased aspartate aminotransferase, and a combination of the two. The endpoints were analyzed using logistic regression models. No statistically significant relationship (P > 0.05) was found between isavuconazole exposure and either efficacy or safety endpoints. The lack of association between exposure and efficacy indicates that the isavuconazole exposures achieved by clinical dosing were appropriate for treating the infecting organisms in the SECURE study and that increases in alanine or aspartate aminotransferase were not related to increase in exposures. Without a clear relationship, there is no current clinical evidence for recommending routine therapeutic drug monitoring for isavuconazole.

Mycotic Infections in the Compromised Host

2013 ◽  
Author(s):  
Jo-Anne H. Young
Keyword(s):  
Fungal Infections ◽  
Fusarium Species ◽  
Diagnostic Testing ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Bimodal Distribution ◽  
Dematiaceous Fungi ◽  
Pneumocystis Jiroveci ◽  
Compromised Host ◽  
Pneumocystis Jiroveci Pneumonia ◽  
Mycotic Infections

Opportunistic fungal infections have become increasingly important over the past several decades, paradoxically because advances in medical practice have improved the survival of debilitated and immunosuppressed patients. The mycotic infections that appear in the compromised host are candidiasis, cryptococcosis, pneumocystosis, aspergillosis, zygomycosis, and fusariosis. The aspergillosis section addresses allergic bronchopulmonary aspergillosis and invasive aspergillosis separately. Timely diagnosis of opportunistic fungal infection depends on understanding host characteristics, environmental risk factors, clinical presentation, and diagnostic testing, which each section covers. There is also a section on infection by dematiaceous fungi. Figures illustrate the cysts of Pneumocystis and the bimodal distribution of Aspergillus infection after bone marrow transplantation. Tables describe the desensitization of adult patients with sulfa allergy; the stages of allergic bronchopulmonary aspergillosis; the treatment of infections caused by Candida, Cryptococcus, Aspergillus, and Fusarium species; and the treatment and prophylaxis of Pneumocystis jiroveci pneumonia.  This review contains 2 highly rendered figures, 7 tables, and 108 references.

Clinical experience with SUBA-itraconazole at a tertiary paediatric hospital

2020 ◽  
Vol 76 (1) ◽  
pp. 249-252
Author(s):  
Joanne Abbotsford ◽  
David A Foley ◽  
Zoy Goff ◽  
Asha C Bowen ◽  
Christopher C Blyth ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Dose Adjustment ◽  
Fungal Infections ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Serum Levels ◽  
Therapeutic Drug ◽  
Drug Levels ◽  
Paediatric Hospital ◽  
Oral Formulations ◽  
Cutaneous Fungal Infection

Abstract Background Itraconazole remains a first-line antifungal agent for certain fungal infections in children, including allergic bronchopulmonary aspergillosis (ABPA) and sporotrichosis, but poor attainment of therapeutic drug levels is frequently observed with available oral formulations. A formulation of ‘SUper BioAvailability itraconazole’ (SUBA-itraconazole; Lozanoc®) has been developed, with adult studies demonstrating rapid and reliable attainment of therapeutic levels, yet paediatric data are lacking. Objectives To assess the safety, efficacy and attainment of therapeutic drug levels of the SUBA-itraconazole formulation in children. Methods A single-centre retrospective cohort study was conducted, including all patients prescribed SUBA-itraconazole from May 2018 to February 2020. The recommended initial treatment dose was 5 mg/kg twice daily (to a maximum of 400 mg/day) rounded to the nearest capsule size and 2.5 mg/kg/day for prophylaxis. Results Nineteen patients received SUBA-itraconazole and the median age was 12 years. The median dose was 8.5 mg/kg/day and the median duration was 6 weeks. Indications included ABPA (16 patients), sporotrichosis (1), cutaneous fungal infection (1) and prophylaxis (1). Of patients with serum levels measured, almost 60% (10/17) achieved a therapeutic level, 3 with one dose adjustment and 7 following the initial dose. Adherence to dose-adjustment recommendations amongst the seven patients not achieving therapeutic levels was poor. Of patients with ABPA, 13/16 (81%) demonstrated a therapeutic response in IgE level. SUBA-itraconazole was well tolerated with no cessations related to adverse effects. Conclusions SUBA-itraconazole is well tolerated in children, with rapid attainment of therapeutic levels in the majority of patients, and may represent a superior formulation for children in whom itraconazole is indicated for treatment or prevention of fungal infection.

The Importance of Fluconazole in Treatment of Endogenous Endophtalmitis in Patients Prior Treated Using Negative Pressure Therapy for Wound Closure Contaminated with Meticillin-resistant Staphylococcus aureus

2017 ◽  
Vol 68 (7) ◽  
pp. 1598-1601 ◽  
Author(s):  
Anisia Iuliana Alexa ◽  
Roxana Ciuntu ◽  
Alina Cantemir ◽  
Nicoleta Anton ◽  
Ciprian Danielescu ◽  
...  
Keyword(s):  
Antifungal Agents ◽  
Fungal Infections ◽  
Prolonged Treatment ◽  
Endogenous Endophthalmitis ◽  
Pressure Therapy ◽  
First Case ◽  
Severe Infections ◽  
Pars Plana ◽  
Delay In Treatment ◽  
Vitreous Biopsy

Severe infections with C. albicans should be treated promptly with antifungal agents, any delay in treatment increases the risk of endophthalmitis. The systemic Amphotericin B therapy is the gold standard in the treatment of endophthalmitis, but in the case of fungal infections it has not yet been determined. Numerous studies have shown that the use of Fluconazole is effective in the treatment of fungal endophthalmitis. In this paper, we report two cases (3 eyes) that have been presented for the same accusations of significant decrease of AV (visual acuity), ocular pain and blepharospasm suddenly installed, both of which required urgent antibiotic and intravenous antifungal treatment. Both are diagnosed with endogenous endophthalmitis and vitreous biopsy + VPP (pars plana vitrectomy) are performed, with a negative result of the vitreous culture. In both situations the treatment was with antibiotic and systemic antifungals. Postoperatively, evolution was favorable in the first case and less favorable in the second one. The prognosis depends on the virulence of the microorganisms and the time elapsed until initiation of the treatment. Also, the presence of risk factors such as diabetes, sepsis, recent abdominal surgery (C. Albicans is part of the comesary flora of the digestive tract) have influenced the prognosis decisively. Severe infections with C. albicans should be promptly treated with antifungal agents, any delay in treatment increases the risk of endophthalmitis. Even when prolonged treatment of candidemia is instituted, 3% of patients can develop endogenous endophthalmitis, so ocular evaluation is particularly important for patients immobilized in anesthesia and intensive care units.

Potential of Nanoparticles in Combating Candida Infections

2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani
Keyword(s):  
Targeted Delivery ◽  
Recent Progress ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Fold Increase ◽  
Antifungal Drugs ◽  
Low Toxicity ◽  
Candida Infections ◽  
Made In

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.

Antifúngicos poliénicos. Mecanismo de acción y aplicaciones

2020 ◽  
Vol 63 (2) ◽  
pp. 7-17
Author(s):  
Evelyn Rivera-Toledo ◽  
Alan Uriel Jiménez-Delgadillo ◽  
Patricia Manzano-Gayosso
Keyword(s):  
Antifungal Activity ◽  
Key Words ◽  
Secondary Metabolism ◽  
Amphotericin B ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Variable Number ◽  
Therapeutic Failure ◽  
Morbidity And Mortality ◽  
Clinical Use

The first compounds with specific antifungal activity were identified in the middle of the last century as a product of the secondary metabolism of bacteria of the order Actinomycetales, and their clinical use significantly diminished the morbidity and mortality associated with severe fungal infections. Many of such biosynthetic compounds are characterized by a chemical polygenic structure, with a variable number of carbon-carbon double bonds. Currently, besides polygenic antimycotics, there are other antifungal agents, such as the azole compounds, that have less toxicity in patients; however, cases of therapeutic failure with such compounds have been documented, therefore, the use of polygenics is still the best alternative in such cases. This review presents data about the properties and applications of antifungal-polygenic compounds using amphotericin B as a model. Key words: Amphotericin B; antifungal polyenes; ergosterol

scholarly journals Allergic Diseases Caused by Aspergillus Species in Patients with Cystic Fibrosis

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 357
Author(s):  
Aidan K. Curran ◽  
David L. Hava
Keyword(s):  
Cystic Fibrosis ◽  
Fungal Infections ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Hyphal Growth ◽  
Allergic Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Th2 Immune Response ◽  
Difficulty Breathing ◽  
Oral Corticosteroids

Aspergillus spp. are spore forming molds; a subset of which are clinically relevant to humans and can cause significant morbidity and mortality. A. fumigatus causes chronic infection in patients with chronic lung disease such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). In patients with CF, A. fumigatus infection can lead to allergic disease, such as allergic bronchopulmonary aspergillosis (ABPA) which is associated with high rates of hospitalizations for acute exacerbations and lower lung function. ABPA results from TH2 immune response to Aspergillus antigens produced during hyphal growth, marked by high levels of IgE and eosinophil activation. Clinically, patients with ABPA experience difficulty breathing; exacerbations of disease and are at high risk for bronchiectasis and lung fibrosis. Oral corticosteroids are used to manage aspects of the inflammatory response and antifungal agents are used to reduce fungal burden and lower the exposure to fungal antigens. As the appreciation for the severity of fungal infections has grown, new therapies have emerged that aim to improve treatment and outcomes for patients with CF.

scholarly journals Software for Dosage Individualization of Voriconazole for Immunocompromised Patients

2013 ◽  
Vol 57 (4) ◽  
pp. 1888-1894 ◽  
Author(s):  
William W. Hope ◽  
Michael VanGuilder ◽  
J. Peter Donnelly ◽  
Nicole M. A. Blijlevens ◽  
Roger J. M. Brüggemann ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Fungal Infections ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Cell Transplant ◽  
Multiple Model ◽  
Pharmacokinetic Variability ◽  
Hematopoietic Stem ◽  
Wide Range

ABSTRACTThe efficacy of voriconazole is potentially compromised by considerable pharmacokinetic variability. There are increasing insights into voriconazole concentrations that are safe and effective for treatment of invasive fungal infections. Therapeutic drug monitoring is increasingly advocated. Software to aid in the individualization of dosing would be an extremely useful clinical tool. We developed software to enable the individualization of voriconazole dosing to attain predefined serum concentration targets. The process of individualized voriconazole therapy was based on concepts of Bayesian stochastic adaptive control. Multiple-model dosage design with feedback control was used to calculate dosages that achieved desired concentration targets with maximum precision. The performance of the software program was assessed using the data from 10 recipients of an allogeneic hematopoietic stem cell transplant (HSCT) receiving intravenous (i.v.) voriconazole. The program was able to model the plasma concentrations with a high level of precision, despite the wide range of concentration trajectories and interindividual pharmacokinetic variability. The voriconazole concentrations predicted after the last dosages were largely concordant with those actually measured. Simulations provided an illustration of the way in which the software can be used to adjust dosages of patients falling outside desired concentration targets. This software appears to be an extremely useful tool to further optimize voriconazole therapy and aid in therapeutic drug monitoring. Further prospective studies are now required to define the utility of the controller in daily clinical practice.

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