Transcriptome in Human Mycoses

Mycoses are infectious diseases caused by fungi, which incidence has increased in recent decades due to the increasing number of immunocompromised patients and improved diagnostic tests. As eukaryotes, fungi share many similarities with human cells, making it difficult to design drugs without side effects. Commercially available drugs act on a limited number of targets and have been reported fungal resistance to commonly used antifungal drugs. Therefore, elucidating the pathogenesis of fungal infections, the fungal strategies to overcome the hostile environment of the host, and the action of antifungal drugs is essential for developing new therapeutic approaches and diagnostic tests. Large-scale transcriptional analyses using microarrays and RNA sequencing (RNA-seq), combined with improvements in molecular biology techniques, have improved the study of fungal pathogenicity. Such techniques have provided insights into the infective process by identifying molecular strategies used by the host and pathogen during the course of human mycoses. This chapter will explore the latest discoveries regarding the transcriptome of major human fungal pathogens. Further we will highlight genes essential for host–pathogen interactions, immune response, invasion, infection, antifungal drug response, and resistance. Finally, we will discuss their importance to the discovery of new molecular targets for antifungal drugs. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.

PULMONARY ARTERY PSEUDOANEURYSM (PAP) AND MASSIVE HEMOPTYSIS AS A COMPLICATION OF MUCORMYCOSIS AND COVID-19 PNEUMONIA

SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: PAP is a rare entity that can occur secondary to infection, malignancy, or trauma. Mucormycosis in the setting of Covid-19 pneumonia has been increasingly recognized but PAP has only recently been reported in this setting. CASE PRESENTATION: A 44 year-old man with type 2 diabetes, non-ischemic cardiomyopathy, hypothyroidism, and ulcerative colitis presented with dyspnea and cough in July 2021. He was diagnosed with Covid-19 pneumonia and initially treated with molnupiravir. Eight days later he presented to the emergency room with worsening dyspnea, hypoxemia and diabetic ketoacidosis. He required 3L of oxygen and was intubated for airway protection. CT chest revealed mild bilateral patchy opacities and dexamethasone was started. Unfortunately, persistent fevers and worsening respiratory status ensued and repeat chest CT on hospital day (HD) 8 showed a new large left upper lobe (LUL) cavitary lesion. Cultures ultimately grew Rhizopus microsporus and he was started on amphotericin then isavuconazole after acute kidney injury developed. Dexamethasone was discontinued and interval imaging after ten days showed dramatic growth of the cavitary lesion (9 x 6 x 3 cm) with new extension through the chest wall, infiltrating the intercostal spaces and pectoralis muscle. Due to ventilator dependency a tracheostomy was performed on HD 24. Despite anti-fungal therapy the cavitary lesion persisted, with evidence of osseous destruction of the third and fourth ribs, as well as new fluid collections within the cavity and hilar extension. On HD 46 he was transferred to our institution for Thoracic Surgery and Interventional Radiology (IR) evaluations. Percutaneous drain placement followed by pneumonectomy vs. staged cavernostomy was considered;however, on HD 50, the patient suddenly developed massive hemoptysis. CTA of the chest showed a 1.6 x 1.5 cm PAP with active hemorrhage from the LUL anterior segmental artery with dispersion into the cavity. Urgent coil and glue embolization was successfully performed by IR. Ultimately, thoracic surgical intervention was deemed too high risk and thus he was medically managed with a regimen of isavuconazole, amphotericin, and terbinafine. Hemoptysis did not recur and he was eventually discharged from the hospital and liberated from both mechanical ventilation and tracheostomy. Chest CT 6 months from the initial diagnosis has shown stable to mildly decreased size of the cavitary lesion. DISCUSSION: This is the first case to our knowledge of PAP as a complication of Covid-19 and Mucor superinfection in the United States. Five cases of this combination have been recently reported in other countries. Risk factors for Mucor infection after Covid appear to be uncontrolled diabetes, DKA, and steroid administration. CONCLUSIONS: A high index of suspicion should be maintained in patients with these risk factors, as PAP can present as massive hemoptysis and is often fatal. Reference #1: Hoenigl M, Seidel D, Carvalho A, et al. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries [ 2022 Jan 25]. Lancet Microbe. 2022;10.1016/S2666-5247(21)00237-8. doi:10.1016/S2666-5247(21)00237-8 Reference #2: Pruthi H, Muthu V, Bhujade H, et al. Pulmonary Artery Pseudoaneurysm in COVID-19-Associated Pulmonary Mucormycosis: Case Series and Systematic Review of the Literature. Mycopathologia. 2022;187(1):31-37. doi:10.1007/s11046-021-00610-9 Reference #3: Coffey MJ, Fantone J 3rd, Stirling MC, Lynch JP 3rd. Pseudoaneurysm of pulmonary artery in mucormycosis. Radiographic characteristics and management. Am Rev Respir Dis. 1992;145(6):1487-1490. doi:10.1164/ajrccm/145.6.1487 DISCLOSURES: No relevant relationships by Kevin Patel No relevant relationships by Clifford Sung

What to expect when AGEP is induced by terbinafine? Case report and critical review of the literature.

BACKGROUND: Acute Generalised Exanthematous Pustulosis (AGEP) is a rash with multiple sterile intraepidermal or subcorneal non-follicular pustules on edematous papules, with a sudden development and rapid evolution, triggered by drugs, vaccination, insect bites, exposure to mercury, and allergens. OBJECTIVES AND METHODS: We describe a female patient who developed extensive and abnormally prolonged AGEP following exposure to terbinafine and SARS-CoV vaccine. A detailed review of terbinafine-induced-AGEP cases was performed, with the aim of evaluating if the AGEP criteria would follow a different pattern when the disease is triggered by this drug. A PubMed search helped retrieve all terbinafine-induced AGEP case reports. AGEP-specific Sideroff criteria were analysed in terbinafine-induced cases and compared to other trigger causes. CONCLUSIONS: When the AGEP causative drug was terbinafine, a delay in recovery was observed, compared to the existing AGEP criteria when other causes are considered. Terbinafine frequently leads to delayed resolution AGEP probably due to the presence of the drug in the skin for several weeks after exposure, even after discontinuation, and the disease severity may be potentialised by additional factors such as concomitant viral infections or vaccination.

Abstracts from Pharmacology 2021

The proceedings contain 36 papers. The topics discussed include: comparative efficacy and safety of systemic terbinafine and itraconazole in recalcitrant tinea cruris patients;therapeutic potential of fluvoxamine in covid-19 outpatients: a case report;gabapentinoids and opioids tapering tool box (GOTT): midtrial evaluation;clinical trial design optimization and dose rationale for the treatment of buruli ulcer antibiotic combination therapy;antipsychotic use and pneumonia-related mortality;are pharmacogenetic studies ethnically diverse?;2,4-dinitrophenol international trends in systemic exposures reported to poisons centers;and a prospective assessment of patient-reported and objectively measured antihypertensive adherence in a tertiary-referral hypertension clinic.

Terbinafine-induced liver toxicity in the context of a SARS-CoV-2 pandemic: A case report

Terbinafine is a drug that can induce acute liver damage. We present the case of a 40-year-old male patient who developed liver dysfunction after 35 days of terbinafine treatment for onychomycosis. The anatomopathological study showed: acute hepatitis in resolution, in addition to ductopenia and cholestasis. These findings, without a history of viral or autoimmune hepatitis, are consistent with the diagnosis of drug-induced liver damage (DILI). In this report we present the first case in our country of a patient who is affected by an acute liver disease: terbinafine-induced liver injury, to which SARS-CoV-2 infection was later associated in the context of a pandemic.