SUBA-itraconazole in the treatment of systemic fungal infections.

Conventional itraconazole (c-ITZ) can be used for a variety of fungal infections although variable absorption has been a significant limitation. Super-bioavailable itraconazole (SUBA-ITZ) is a novel formulation that overcomes absorption concerns by utilizing a polymer-matrix to disperse active drug and facilitate dissolution. The pH-driven matrix allows concurrent proton pump inhibitor administration without significant effects on drug concentrations. The enhanced bioavailability of SUBA-ITZ allows for lower dosing, while achieving similar serum concentrations as c-ITZ and SUBA-ITZ is now US FDA approved in the treatment of blastomycosis, histoplasmosis and aspergillosis. Common side effects of SUBA-ITZ include gastrointestinal disorders, peripheral edema and drug-induced hypertension. Given the significant differences in pharmacokinetics between the formulations, c-ITZ and SUBA-ITZ capsules are not considered interchangeable. It is important to note that drug errors may occur when transitioning a patient from one formulation to another.

Itraconazole is an antifungal agent used in the treatment of a number of mycoses. Prior formulations (versions) of itraconazole required strict dietary requirements and often had poor absorption. A new itraconazole formulation has since been developed ­ super bioavailable itraconazole (SUBA-itraconazole). This has no food requirements, has superior absorption and maintains effectiveness against a number of fungal infections.

Battling the breath-stealers: Blastomyces and Pseudomonas triggering acute respiratory distress syndrome (ARDS).

Blastomycosis is an endemic disease in North America and commonly manifests with pulmonary symptoms. Blastomycosis should be consider when patients have persistent infiltrates on imaging in an endemic area. We present a case of a 46-year-old male who presented to the pulmonary clinic with fever, cough with production of yellowish-green sputum and culture of BAL-fluid showed growth of Pseudomonas spp. Antimicrobial therapy was started accordingly, but was not effective. A repeat bronchoscopy was performed and BAL-fluid culture was positive for Blastomyces dermatitidis and liposomal amphotericin B was initiated. Unfortunately, the patient died after withdrawing care.

Extrahepatic cholestasis associated with paracoccidioidomycosis: Challenges in the differential diagnosis of biliopancreatic neoplasia.

BACKGROUND: Paracoccidioidomycosis (PCM) may involve the hepatic pedicle and peripancreatic lymph nodes, cause damage to the bile duct and manifest, exceptionally, in combination with extrahepatic cholestasis (EHC), making investigation and treatment challenging. AIM: To investigate the management of patients with visceral PCM admitted with EHC. METHODS: All patients diagnosed with PCM treated in a public, tertiary teaching hospital between 1982 and 2020 were retrospectively evaluated. Those also identified with EHC were allocated to two groups according to the treatment approach for the purpose of comparing clinical, laboratory, and imaging findings, resources used for etiological diagnosis, treatment results, and prognosis. Statistical analyses were performed using the linear mixed-effects model (random and fixed effects), which was adjusted using the PROC MIXED procedure of the SAS® 9.0 software, and Fisher's exact test. RESULTS: Of 1645 patients diagnosed with PCM, 40 (2.4%) had EHC. Of these, 20 (50.0%) lived in the rural area and 29 (72.5%) were men, with a mean age of 27.1 years (3-65 years). Jaundice as first symptom and weight loss of at least 10 kg were observed in 16 patients (40.0%), and a mass in the head of the pancreas was observed in 8 (20.0%). The etiological diagnosis was made by tissue collection during surgery in 4 cases (10.0%) and by endoscopic methods in 3 cases (7.5%). Twenty-seven patients (67.5%) received drug treatment alone (Group 1), whereas 13 (32.5%) underwent endoscopic and/or surgical procedures in combination with drug treatment (Group 2). EHC was significantly reduced in both groups (40.7% in Group 1, with a mean time of 3 months; and 38.4% in Group 2, with a mean time of 7.5 months), with no statistically significant difference between them. EHC recurrence rates, associated mainly with treatment nonadherence, were similar in both groups: 37% in Group 1 and 15.4% in Group 2. The mortality rate was 18.5% in Group 1 and 23% in Group 2, with survival estimates of 71.3% and 72.5%, respectively, with no statistically significant difference. CONCLUSION: Although PCM-related EHC is rare, it needs to be included in the differential diagnosis of malignancies, as timely treatment can prevent hepatic and extrahepatic sequelae.

Disseminated Blastomycosis in an Immunocompetent Patient.

Blastomycoses dermatitidis is a dimorphic fungus that can cause disseminated blastomycosis with varying clinical manifestations and multiorgan involvement. While blastomycosis commonly causes pulmonary disease, extrapulmonary spread can result in skin, bone, and central nervous system involvement. Cutaneous blastomycosis can present as pustular lesions that evolve into ulcerative or verrucous plaques. We present a case of disseminated blastomycosis in an immunocompetent patient with both pulmonary and cutaneous features. The patient developed hypoxic respiratory failure and was subsequently diagnosed with disseminated blastomycosis after undergoing bronchoscopy with bronchial washing. He was found to have ulcerative nasal lesions as part of his disseminated disease. He was successfully treated with amphotericin B and ultimately discharged from the hospital.

Case series of dogs with blastomycosis managed with high-flow nasal oxygen therapy (2019-2023): 19 cases.

Objective: To describe the clinical presentation, progression, treatment, and outcome of dogs with blastomycosis treated with high-flow nasal oxygen therapy (HFNOT). Design: Retrospective case review. Setting: University veterinary teaching hospital. Animals: Nineteen client-owned dogs with strongly suspected or confirmed blastomycosis treated with HFNOT. Measurements and main results: The medical records of dogs with strongly suspected or confirmed blastomycosis between October 2019 and May 2023 that received HFNOT were evaluated. Nineteen dogs were included. Nine dogs were started directly on high-flow nasal oxygen therapy. The remaining 10 dogs first received traditional oxygen therapy and were then transitioned to HFNOT 3-142 h later. Of the 19 dogs, 1 survived to discharge from hospital, 12 were euthanized due to progression of disease, and 6 died during the hospitalization period. Conclusions and clinical importance: The prognosis for survival of dogs with severe blastomycosis requiring therapy beyond traditional oxygen methods was poor to grave in this population. This is the first known documented report of HFNOT use in dogs with confirmed or suspected blastomycosis.

Genomic Epidemiology of Large Blastomycosis Outbreak, Ontario, Canada, 2021.

Using phylogenomic analysis, we provide genomic epidemiology analysis of a large blastomycosis outbreak in Ontario, Canada, caused by Blastomyces gilchristii. The outbreak occurred in a locale where blastomycosis is rarely diagnosed, signaling a possible shift in geographically associated incidence patterns. Results elucidated fungal population genetic structure, enhancing understanding of the outbreak.

Proceedings of the Second International Meeting on Endemic Mycoses of the Americas (IMEMA), and First International Symposium on Implantation Mycoses (ISIM).

The Second International Meeting on Endemic Mycoses of the Americas (IMEMA) and the First International Symposium on Implantation Mycoses (ISIM) took place in Santiago del Estero, Argentina during September 25-27th, 2023. The conference provided a platform for researchers, clinicians, and experts to discuss the latest developments in the field of endemic and implantation mycoses. Topics included epidemiology, diagnostic advances, treatment strategies, and the impact of environmental factors in the spread of these fungal diseases. IMEMA and ISIM contributed to the regional discourse on the mycoses, emphasizing the importance of international cooperation in addressing these public health challenges.

IMEMA/ISIM, held in Santiago del Estero, Argentina, convened experts to discuss endemic and implantation mycoses, covering topics such as epidemiology, diagnostics, treatment, and advocacy. The event highlighted ongoing efforts in combating these diseases.

Endemic Fungal Infective Endocarditis Caused by Coccidioides, Blastomyces and Histoplasma Species in the United States.

We describe a recent case of Coccidioides bioprosthetic aortic valve infective endocarditis successfully managed at our institution. This led us to perform a literature review of endemic fungal infective endocarditis in the United States caused by Coccidioides, Blastomyces, and Histoplasma. Symptoms preceded infective endocarditis diagnosis by several months. Patients with Coccidioides and Blastomyces infective endocarditis were younger with fewer comorbid conditions. Valvular involvement was relatively uncommon in Blastomyces infective endocarditis (27%). Fungemia was noted in patients with infective endocarditis due to Histoplasma (30%) and Coccidioides (18%). Mortality rates for infective endocarditis were high (Histoplasma, 46%; Coccidioides, 58%; Blastomyces, 80%); infective endocarditis was commonly diagnosed post-mortem (Coccidioides, 58%; Blastomyces, 89%). Most surviving patients with infective endocarditis (Histoplasma, 79%; Coccidioides, 80%) underwent valve surgery along with prolonged antifungal therapy. The two surviving patients with Blastomyces infective endocarditis received antifungal therapy without surgery.

Clinical Presentation of Blastomycosis is Associated With Infecting Species, Not Host Genotype.

Objective: To determine if host genetics may be a risk factor for severe blastomycosis.Design: A cohort of patients who had contracted blastomycosis underwent targeted SNP (single nucleotide polymorphism) genotyping. The genetics of these patients were compared to a set of age and gender-matched controls and between patients with severe versus mild to moderate blastomycosis.Setting: The Marshfield Clinic Health System in central and northern WisconsinParticipants: Patients with a diagnosis of blastomycosis prior to 2017 were contacted for enrollment in this study. A phone hotline was also set up to allow interested participants from outside the Marshfield Clinic Health System to request enrollment.Methods: SNP frequency was assessed for significant differences between the patient cohort and controls and between patients with severe versus mild to moderate blastomycosis. We also tested the effect of Blastomyces species identified in clinical isolates on disease symptoms and severity.Results: No significant differences were found in SNP frequency between cases and controls or between those with severe or mild to moderate blastomycosis. We did detect significant differences in symptom frequency and disease severity by Blastomyces species.Conclusions: Our study did not identify any genetic risk factors for blastomycosis. Instead, the species of Blastomyces causing the infection had a significant effect on disease severity.

MSG-15: Super-Bioavailability Itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses-A Multicenter, Open-Label, Randomized Comparative Trial.

Background: Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis). Methods: This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180. Results: Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) caused by Histoplasma (n = 51), Blastomyces (n = 18), Coccidioides (n = 13), or Sporothrix (n = 6). On day 42, clinical success was observed with SUBA-itra and c-itra on day 42 (in 69% and 67%, respectively, and on day 180 (in 60% and 65%). Patients treated with SUBA-itra exhibited less drug-level variability at days 7 (P = .03) and 14 (P = .06) of randomized treatment. The concentrations of itraconazole and hydroxyitraconazole were comparable between the 2 medications (P = .77 and P = .80, respectively). There was a trend for fewer adverse events (AEs; 74% vs 87%, respectively; P = .18) and serious AEs (10% vs 26%; P = .06) in the SUBA-itra-treated patients than in those receiving c-itra. Serious treatment-emergent AEs were less common in SUBA-itra-treated patients (12% vs 50%, respectively; P < .001). Conclusions: SUBA-itra was bioequivalent, well tolerated, and efficacious in treating endemic fungi, with a more favorable safety profile than c-itra. Clinical Trials Registration: NCT03572049.

Beware of the Acute Respiratory Distress Syndrome in a Pulmonary Blastomycosis!

Blastomyces dermatitidis is a dimorphic fungus that can range from mild to severe disease presentation, including the acute respiratory distress syndrome (ARDS) based on the individual's immunity. Acute respiratory distress syndrome is an uncommon presentation having an incidence of about 10% to 15% but has a high mortality exceeding 90%. This is a case of a 50-year-old female with past medical history of asthma and type 2 diabetes mellitus who presented to the pulmonology clinic with worsening dyspnea for the last 2 months. She also had a lesion in the left lower back, which was draining purulent fluid. Chest radiographs showed bilateral infiltrates and was started empirically on vancomycin and piperacillin-tazobactam. Bronchoalveolar lavage was done and the cultures grew B dermatitidis. The patient was moved to a higher level of care and given amphotericin B. Unfortunately, the patient experienced septic shock, which later deteriorated into cardiac arrest, ultimately leading to their passing. The importance of early diagnosis of blastomycosis and timely treatment has been emphasized in this case report.

Acute Dyspnea With an Infiltrative Tracheal Mass.

CASE PRESENTATION: A 48-year-old woman presented to the ED with a nonproductive cough, shortness of breath, and stridor. She was otherwise healthy and had never used tobacco. The patient was mildly tachycardic but otherwise hemodynamically stable, afebrile, and saturating well on room air. She did not display any signs of increased work of breathing at rest. Although auscultation of her thorax indicated good air entry bilaterally without any adventitious sounds, stridor was elicited with forced expiration.

Blastomycosis Complicated by Adult Respiratory Distress Syndrome in an Immunocompetent Adult: A Case Report and Literature Review.

Blastomycosis is an endemic mycotic infection caused by inhalation of thermally dimorphic fungi from the genus Blastomyces. Blastomyces dermatitidis is the species most related to human infection in the USA and North America. Adult respiratory distress syndrome (ARDS) is a rare complication of blastomycosis and is associated with high mortality. Due to its rarity, evidence-based guidelines for diagnosing and treating ARDS associated with blastomycosis are scarce. In this case presentation, a 22-year-old male with a history of chronic cannabis use presented with severe respiratory symptoms, initially treated as community-acquired pneumonia. Despite antibiotic treatment, his condition deteriorated, necessitating intubation and resulting in the development of ARDS. A delayed diagnosis of pulmonary blastomycosis was confirmed through polymerase chain reaction testing. Treatment with amphotericin B and corticosteroids proved successful in addressing the fungal infection, leading to the recovery of the patient from his severe clinical condition. This case highlights the challenges associated with diagnosing and treating blastomycosis, particularly when complicated by ARDS, emphasizing the importance of considering fungal infections in the differential diagnosis of non-responsive pulmonary infections. Additionally, it suggests the potential utility of corticosteroids in severe cases and emphasizes the crucial role of early diagnosis and a combination of diagnostic modalities for the timely management of this rare and potentially life-threatening condition.

A Rare Case of Uterine Blastomycosis and Its Management: A Case Report and Literature Review.

The report delineates the rare occurrence of uterine blastomycosis, an atypical systemic presentation of Blastomyces dermatitidis infection prevalent in North America. Focused on a 51-year-old immunocompetent female displaying abdominal pain and irregular vaginal bleeding, it underscores the intricate diagnostic hurdles posed by symptoms mirroring common gynecological conditions. Despite fewer than 10 recorded cases, the rarity of uterine involvement highlights the imperative for heightened clinical suspicion. The multifaceted diagnostic strategy integrates risk factors, travel history, imaging, and histopathological examinations. Emphasizing a multidisciplinary treatment helmed by gynecologists, pathologists, and infectious disease specialists, the utilization of antifungal agents, notably itraconazole, is pivotal. Addressing the scarcity of literature and the condition's clinical resemblance to prevalent ailments, further research becomes paramount in devising tailored diagnostic and treatment protocols for uterine blastomycosis. This study enriches the existing literature by providing critical insights into a scarcely documented condition, contributing novel perspectives essential for clinical understanding and management strategies.

Using Insurance Claims Data to Estimate Blastomycosis Incidence, Vermont, USA, 2011-2020.

The epidemiology of blastomycosis in Vermont, USA, is poorly understood. Using insurance claims data, we estimated the mean annual blastomycosis incidence was 1.8 patients/100,000 persons during 2011-2020. Incidence and disease severity were highest in north-central counties. Our findings highlight a need for improved clinical awareness and expanded surveillance.

Detection of Blastomyces gilchristii via metagenomic sequencing in outbreak-associated soils.

Cases of blastomycosis, a serious fungal disease globally rare but endemic to North America, can appear both sporadically and in outbreaks. Tracing these outbreaks to their environment has traditionally used culturing and polymerase chain reaction. Here, we present our method for metagenomic detection of Blastomyces in a 2015 outbreak soil sample from central Wisconsin. By sequencing this sample to multiple depths, we simulated the minimum required depth to detect Blastomyces in this outbreak. Our methods and recommendations can be used to identify the sources of blastomycosis during outbreaks and to learn about the ecology of Blastomyces.