Taxonomy, biology, and clinical aspects of Fusarium species.

There are several taxonomic systems available for identifying Fusarium species. The philosophy used in each taxonomic system is discussed as well as problems encountered in working with Fusarium species in culture. Fusarium species are toxigenic, and the mycotoxins produced by these organisms are often associated with animal and human diseases. The implications for the association of the carcinogens, fumonisins, produced by Fusarium moniliforme and other Fusarium species with human diseases are discussed. Foreign-body-associated fusarial infection such as keratitis in contact lens wearers, onychomycosis, skin infections, and disseminated multiorgan infections are discussed. Disseminated fusarial hyalohyphomycosis has emerged as a significant, usually fatal infection in the immunocompromised host. Successful outcome is determined by the degree of immunosuppression, the extent of the infection, and the presence of a removable focus such as an indwelling central venous catheter. These infections may be clinically suspected on the basis of a constellation of clinical and laboratory findings, which should lead to prompt therapy, probably with one of the newer antifungal agents. Perhaps the use of such agents or the use of colony-stimulating factors may improve the outcome of this devastating infection. However, until new approaches for treatment develop, effective preventive measures are urgently needed.

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1157. Clinical Safety, Efficacy, and Pharmacokinetics of Fosmanogepix, a Novel First-in-class Antifungal, in Patients with Renal Insufficiency: Subset Analysis from a Phase 2 Candidemia Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1343 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S605-S605

Author(s):

Pierre Bulpa ◽

Galia Rahav ◽

Ilana Oren ◽

Mickaël Aoun ◽

George R Thompson ◽

...

Keyword(s):

Renal Function ◽

Renal Insufficiency ◽

Antifungal Agents ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Antifungal Treatment ◽

Successful Outcome ◽

Review Panel ◽

Study Investigator

Abstract Background Fosmanogepix (FMGX) is a first-in-class antifungal agent, with a unique MOA targeting the fungal enzyme Gwt1, and broad-spectrum activity against yeasts and molds, including fungi resistant to other antifungal agents. Patients with candidemia often have underlying renal insufficiency or are receiving medications that affect renal function. This analysis evaluated outcomes in patients with varying degrees of renal insufficiency. Methods This global, multicenter, open-label, non-comparative study evaluated the safety and efficacy of FMGX for first-line treatment of candidemia. Patients with a recent diagnosis of candidemia defined as positive blood culture for Candida spp within 96 hrs prior to study entry with ≤ 2 days of prior antifungal treatment were eligible, including those with renal insufficiency. Patients with neutropenia, C. krusei infection, deep-seated Candida infections or receiving hemodialysis were excluded. Subjects were treated with FMGX for up to 14 days: 1000 mg IV BID for 1 day, then 600 mg IV QD for at least 2 days, followed by either 600 mg IV QD or 700 mg PO QD. Patients requiring antifungal treatment beyond 14 days received fluconazole. The primary efficacy endpoint was outcome at end of study treatment (EOST) as determined by an independent data review committee. Successful outcome was defined as survival with clearance of Candida from blood cultures with no additional antifungal treatment. Results 14/21 (66%) subjects had some degree of renal insufficiency: 7 had mild renal insufficiency (GFR:60-89), 5 had moderate renal insufficiency (GFR:30-59), and 2 had severe renal insufficiency (GFR:15-29). 12/14 (86%) completed study treatment, and treatment was successful at EOST in 12/14 (86%) subjects. Decline in renal function was not observed at EOST. 4 had worsening of renal function during the follow-up period; none required dialysis. Renal impairment did not increase exposure of FMGX. There were no treatment-related adverse events. Conclusion FMGX demonstrated high level treatment success with no evidence of drug-related nephrotoxicity, with no dose adjustments required. These preliminary data support the continued evaluation of FMGX in patients with candidemia and renal dysfunction as an alternative to potentially nephrotoxic antifungal agents. Disclosures Pierre Bulpa, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Galia Rahav, MD, AstraZeneca (Scientific Research Study Investigator) Mickaël Aoun, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Bart Jan Kullberg, MD, FRCP, FIDSA, Amplyx (Advisor or Review Panel member) Sara Barbat, BSN, RN, Amplyx Pharmaceuticals (Employee) Pamela Wedel, BSc, Amplyx Pharmaceuticals (Employee) Haran T. Schlamm, MD, Amplyx (Consultant) Michael Hodges, BSc. MD, Amplyx Pharmaceuticals Inc. (Employee)

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Indwelling Device-Associated Biofilms in Critically Ill Cancer Patients—Study Protocol

Pathogens ◽

10.3390/pathogens10030306 ◽

2021 ◽

Vol 10 (3) ◽

pp. 306

Author(s):

Olguta Lungu ◽

Ioana Grigoras ◽

Olivia Simona Dorneanu ◽

Catalina Lunca ◽

Teodora Vremera ◽

...

Keyword(s):

Cancer Patients ◽

Critically Ill ◽

Pathogen Detection ◽

Venous Catheter ◽

Successful Outcome ◽

Patient Specific ◽

Clinical Value ◽

Current Standard ◽

Sepsis Management ◽

Microorganism Identification

Health care-associated infections are a leading cause of inpatient complications. Rapid pathogen detection/identification is a major challenge in sepsis management that highly influences the successful outcome. The current standard of microorganism identification relies on bacterial growth in culture, which has several limitations. Gene sequencing research has developed culture-independent techniques for microorganism identification, with the aim to improve etiological diagnosis and, therefore, to change sepsis outcome. A prospective, observational, non-interventional, single-center study was designed that assesses biofilm-associated pathogens in a specific subpopulation of septic critically ill cancer patients. Indwelling device samples will be collected in septic patients at the moment of the removal of the arterial catheter, central venous catheter, endotracheal tube and urinary catheter. Concomitantly, clinical data regarding 4 sites (nasal, pharyngeal, rectal and skin) of pathogen colonization at the time of hospital/intensive care admission will be collected. The present study aims to offer new insights into biofilm-associated infections and to evaluate the infection caused by catheter-specific and patient-specific biofilm-associated pathogens in association with the extent of colonization. The analysis relies on the two following detection/identification techniques: standard microbiological method and next generation sequencing (NGS). Retrospectively, the study will estimate the clinical value of the NGS-based detection and its virtual potential in changing patient management and outcome, notably in the subjects with missing sepsis source or lack of response to anti-infective treatment.

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Severe Posaconazole-Induced Glucocorticoid Deficiency with Concurrent Pseudohyperaldosteronism: An Unfortunate Two-for-One Special

Journal of Fungi ◽

10.3390/jof7080620 ◽

2021 ◽

Vol 7 (8) ◽

pp. 620

Author(s):

Alejandro Villar-Prados ◽

Julia J. Chang ◽

David A. Stevens ◽

Gary K. Schoolnik ◽

Samantha X. Y. Wang

Keyword(s):

Mechanism Of Action ◽

Antifungal Agents ◽

Laboratory Findings ◽

Steroid Synthesis ◽

Adrenal Steroid ◽

History Of ◽

Glucocorticoid Deficiency

A 56-year-old Hispanic man with a history of disseminated coccidioidomycosis was diagnosed with persistent glucocorticoid insufficiency and pseudohyperaldosteronism secondary to posaconazole toxicity. This case was notable for unexpected laboratory findings of both pseudohyperaldosteronism and severe glucocorticoid deficiency due to posaconazole’s mechanism of action on the adrenal steroid synthesis pathway. Transitioning to fluconazole and starting hydrocortisone resolved the hypokalemia but not his glucocorticoid deficiency. This case highlights the importance of recognizing iatrogenic glucocorticoid deficiency with azole antifungal agents and potential long term sequalae.

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Epidemiological and clinical aspects of immunoglobulin A vasculitis in childhood: a retrospective cohort study

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01182-6 ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Breda Luciana ◽

Carbone Ilaria ◽

Casciato Isabella ◽

Cristina Gentile ◽

Eleonora Agata Grasso ◽

...

Keyword(s):

Clinical Symptoms ◽

Renal Involvement ◽

Healthcare Delivery ◽

Immunoglobulin A ◽

Retrospective Chart Review ◽

Paediatric Population ◽

Clinical Aspects ◽

Healthcare Delivery System ◽

Laboratory Findings ◽

Immunoglobulin A Vasculitis

Abstract Background A retrospective study was conducted in order to investigate and describe the characteristics of Immunoglobulin A vasculitis (IgAV), previously known as Henoch-Schӧnlein purpura, in the paediatric population of a community-based healthcare delivery system in the Italian region of Abruzzo. Methods This is a population-based retrospective chart review of the diagnosis of IgAV in children ages 0 to 18, admitted to the Department of Paediatrics of Chieti and Pescara between 1 January 2000 and 31 December 2016. All children enrolled presented with clinical symptoms and laboratory findings and met the EULAR/PRINTO/PRES 2008 criteria. Results Two-hundred-eight children met the criteria for IgAV, with the highest incidence reported among children below 7-years of age. A correlation with recent infections was found in 64% of the cohort; the onset was more frequently during the winter and fall. Purpura had a diffuse distribution in the majority of patients; joint impairment was the second most frequent symptom (43%), whereas the gastrointestinal tract was involved in 28% of patients. Conclusions Hereby, we confirm the relative benignity of IgAV in a cohort of Italian children; with regards to renal involvement, we report a better outcome compared to other studies. However, despite the low rate of renal disease, we observed a wide use of corticosteroids, especially for the treatment of persistent purpura.

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Conventional central venous catheters as tunnelled mid-clavicular midline catheters: Description of novel application and outcome analysis

The Journal of Vascular Access ◽

10.1177/1129729820982870 ◽

2020 ◽

pp. 112972982098287

Author(s):

Sivashanmugam Thiyagarajan ◽

Charulatha Ravindran

Keyword(s):

Blood Stream Infection ◽

Venous Catheter ◽

Venous Access ◽

Blood Stream ◽

Central Venous Catheters ◽

Successful Outcome ◽

Outcome Analysis ◽

Clinical Report ◽

Central Venous ◽

Cost Constraints

Background: Long peripheral catheters are the ideal devices for intermediate venous access (1–4 weeks). However due to non-availability and cost constraints, these lines are not widely adapted in developing countries. In this clinical report we describe a technique of using conventional Central Venous Catheters as Midclavicular midlines for intermediate venous access and present the outcome analysis of such catheters in the last 2 years from our institute. Methods: A single lumen conventional central venous catheter (5 Fr, 20 cm) was introduced through the deep veins of the upper arm, 1 to 1.5 cm distal to the axillary crease. The catheter was tunnelled for a distance of 5 to 7 cm to exit from Dawson’s green zone to reduce the incidence of Midline Associated Blood Stream Infection. Patients were followed up by trained staff nurses and outcome parameters were recorded. Results: Seventy six patients were enrolled and 72 patients underwent successful cannulation and completed the outcome analysis. Administration of intravenous antibiotics and chemotherapy were the commonest indications. The device served the intended duration of therapy in 66 (92%) patients for a median number of 12 (6–20) catheter days. Device related blood stream infection was 1.24/1000 catheter days and catheter related thrombosis rate was 8.3%. Conclusion: Conventional Central Venous Catheters can be effectively used as tunnelled Midclavicular midline catheters in low resource settings. The successful outcome analysis has to be confirmed by larger studies.

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Torulopsis glabrata vaginitis: Clinical aspects and susceptibility to antifungal agents

International Journal of Gynecology & Obstetrics ◽

10.1016/0020-7292(91)90322-v ◽

1991 ◽

Vol 35 (3) ◽

pp. 286-286

Author(s):

V Redondo-Lopez ◽

M Lynch ◽

C Schmitt ◽

R Cook ◽

JD Sobel

Keyword(s):

Antifungal Agents ◽

Clinical Aspects ◽

Torulopsis Glabrata

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Central venous catheter infection associated with Pseudozyma aphidis in a child with short gut syndrome

Journal of Medical Microbiology ◽

10.1099/jmm.0.47563-0 ◽

2008 ◽

Vol 57 (4) ◽

pp. 516-518 ◽

Cited By ~ 25

Author(s):

Shau-Shau Lin ◽

Thomas Pranikoff ◽

Shani F. Smith ◽

Mary E. Brandt ◽

Kemery Gilbert ◽

...

Keyword(s):

Central Venous Catheter ◽

Venous Catheter ◽

Successful Outcome ◽

Smut Fungi ◽

Central Venous ◽

Short Gut Syndrome ◽

Paediatric Case ◽

Pseudozyma Aphidis ◽

Central Venous Catheter Infection ◽

Anti Fungal

Pseudozyma aphidis is a heterobasidiomycetous yeast related to the smut fungi in the genus Ustilago. Pseudozyma species are usually isolated from plants and rarely from clinical specimens. We report what is believed to be the first paediatric case of central venous catheter (CVC)-related fungaemia associated with P. aphidis. Prompt removal of the CVC in conjunction with anti-fungal therapy resulted in a successful outcome.

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The Repurposing of the Antimalaria Drug, Primaquine, as a Photosensitizer to Inactivate Cryptococcal Cells

Photochem ◽

10.3390/photochem1020017 ◽

2021 ◽

Vol 1 (2) ◽

pp. 275-286

Author(s):

Uju L. Madu ◽

Adepemi O. Ogundeji ◽

Olufemi S. Folorunso ◽

Jacobus Albertyn ◽

Carolina H. Pohl ◽

...

Keyword(s):

Exposure Time ◽

Metabolic Activity ◽

Antifungal Agents ◽

Skin Infections ◽

Cryptococcal Infection ◽

Selective Permeability ◽

Infection Treatment ◽

Radiation Output ◽

Uv Lamp

Cryptococcal cells can manifest skin infections in immunocompromised persons. While it may be easy to diagnose cryptococcal infection, treatment often fails due to the ineffectiveness of current antifungal agents. To this end, the present study explored the repurposing of primaquine (PQ), as a photosensitizer. PDT was carried out using a germicidal ultraviolet (UV) lamp, which has a radiation output of approximately 625 µW/cm2 at a distance of 20 cm. When compared to the non-treated cells, the metabolic activity of cryptococcal cells was significantly (p < 0.05) limited. The photolytic products of PQ were observed to alter the ultrastructure of treated cells. The latter was not incidental, as the same cells were also documented to lose their selective permeability. Importantly, PDT also improved the efficiency of macrophages to kill internalized cryptococcal cells (p ≤ 0.05) when compared to non-treated macrophages. Equally importantly, PDT was not detrimental to macrophages, as their metabolic activity was not significantly (p > 0.05) limited, even when exposed to 20× the MIC (determined for cryptococcal cells) and an exposure time that was 4× longer. Taken together, the results suggest PQ has the potential to control the growth of cryptococcal cells and limit their survival inside the macrophage.

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Do high MICs predict the outcome in invasive fusariosis?

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa516 ◽

2020 ◽

Author(s):

Marcio Nucci ◽

Jeffrey Jenks ◽

George R Thompson ◽

Martin Hoenigl ◽

Marielle Camargo dos Santos ◽

...

Keyword(s):

Amphotericin B ◽

Death Rate ◽

Liposomal Amphotericin ◽

Antifungal Agents ◽

Fusarium Species ◽

Primary Treatment ◽

Clear Cut ◽

The Poor ◽

Immunocompromised Hosts ◽

High Mics

Abstract Background Invasive fusariosis (IF) affects mostly severely immunocompromised hosts and is associated with poor outcome. Since Fusarium species exhibit high MICs for most antifungal agents, this could explain the poor prognosis. However, a clear-cut correlation between MIC and outcome has not been established. Objective To evaluate the correlation between MIC and outcome (6 week death rate) in patients with IF. Methods We performed a multicentre retrospective study of patients with IF who received treatment and had MIC levels determined by EUCAST or CLSI for the drug(s) used during treatment. We compared the MIC50 and MIC distribution among survivors and patients who died within 6 weeks from the diagnosis of IF. Results Among 88 patients with IF, 74 had haematological diseases. Primary treatment was monotherapy in 52 patients (voriconazole in 27) and combination therapy in 36 patients (liposomal amphotericin B + voriconazole in 23). The MIC50 and range for the five most frequent agents tested were: voriconazole 8 mg/L (range 0.5–64), amphotericin B 2 mg/L (range 0.25–64), posaconazole 16 mg/L (range 0.5–64), itraconazole 32 mg/L (range 4–64), and isavuconazole 32 mg/L (range 8–64). There was no difference in MIC50 and MIC distribution among survivors and patients who died. By contrast, persistent neutropenia and receipt of corticosteroids were strong predictors of 6 week mortality. Conclusions Our study did not show any correlation between MIC and mortality at 6 weeks in patients with IF.

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