Journal de mycologie medicale最新文献

We report a case with Clavispora lusitaniae-induced purulent thrombophlebitis. The patient had multiple risk factors for the development of fungal thrombophlebitis including surgical procedure, mechanical ventilation, admission to intensive care unit, total parenteral nutrition and long-term antimicrobial therapy in addition to the insertion of central venous catheter. The symptoms finally improved by a combination therapy of micafungin and flucytosine, but the therapy did not rapidly resolve candidemia. The appropriate antifungal therapy for C. lusitaniae-induced purulent thrombophlebitis is uncertain. Further study is desired to seek the appropriate therapy for the disease.

The increasing resistance to antifungal agents associated with toxicity and interactions turns therapeutic management of fungal infections difficult. This scenario emphasizes the importance of drug repositioning, such as nitroxoline – a urinary antibacterial agent that has shown potential antifungal activity. The aims of this study were to discover the possible therapeutic targets of nitroxoline using an in silico approach, and to determine the in vitro antifungal activity of the drug against the fungal cell wall and cytoplasmic membrane. We explored the biological activity of nitroxoline using PASS, SwissTargetPrediction and Cortellis Drug Discovery Intelligence web tools. After confirmation, the molecule was designed and optimized in HyperChem software. GOLD 2020.1 software was used to predict the interactions between the drug and the target proteins. In vitro investigation evaluated the effect of nitroxoline on the fungal cell wall through sorbitol protection assay. Ergosterol binding assay was carried out to assess the effect of the drug on the cytoplasmic membrane. In silico investigation revealed biological activity with alkane 1-monooxygenase and methionine aminopeptidase enzymes, showing nine and five interactions in the molecular docking, respectively. In vitro results exhibited no effect on the fungal cell wall or cytoplasmic membrane. Finally, nitroxoline has potential as an antifungal agent due to the interaction with alkane 1-monooxygenase and methionine aminopeptidase enzymes, which are not the main human therapeutic targets. These results have potentially revealed a new biological target for the treatment of fungal infections. We also consider that further studies are required to confirm the biological activity of nitroxoline on fungal cells, mainly the confirmation of the alkB gene.

Cryptococcal meningitis is a life-threatening infection commonly seen in patients with advanced HIV infection and solid organ transplant recipients. We report a case of cryptococcal meningitis with immune reconstitution syndrome (IRIS) who presented to us with a headache and complete loss of vision in the left eye. He was managed with antifungals and a short course of steroids, and he regained vision completely. In the hospital, he developed complications including tacrolimus toxicity, fluconazole-induced QT prolongation, and flucytosine-induced thrombocytopenia. Our case demonstrates the importance of a multidisciplinary approach in the management of complex cases like cryptococcal meningitis in solid organ transplant recipients.

The increasing incidences of fungal infections among Covid-19 infected patients is a global public concern and urgently demands novel antifungals. Biopolymers like chitosan hold unique structural properties and thus can be utilized in the synthesis of biologically important scaffolds. To address the current scenario, the author's synthesized novel chitosan-azetidine derivative by adopting one-pot multicomponent reaction approach. The influence of chemical modification on the structural characteristics was investigated by means of spectroscopic techniques viz. FT-IR and ¹HNMR and elemental analysis. Additionally, the authors investigated the antifungal potential of chitosan-azetidine derivative against Aspergillus fumigatus 3007 and the results indicated higher antifungal effect with an antifungal inhibitory index of 26.19%. The SEM and confocal microscopy images also reflected a significant inhibitory effect on the morphology of fungal mycelia, thus reflecting the potential of synthesized chitosan-azetidine derivativeas a potential antifungal agent.

Onychomycosis is the most prevalent nail ailment in adults, accounting for 50% of all nail infections. Dermatophyte fungi are the primary cause, but non-dermatophyte molds (NDM) and yeasts can also cause onychomycosis. It remains important to precisely determine the fungal cause of onychomycosis since the response to current treatments may vary between fungal classes. Real-time polymerase chain reaction (qPCR) has become a widespread tool for detecting fungal organisms for diagnosis due to its sensitivity and ability to detect down to the species level. This retrospective study aims to evaluate the qPCR Onycho+ test for dermatophyte detection using remnants of toenails from a cohort of patients from Puerto Rico.  Two hundred forty-two toenail samples submitted for histological examination via Periodic acid Schiff (PAS) staining for suspected onychomycosis were analyzed by the Onycho+ test and Sanger sequencing of the internal transcribed spacer (ITS-2). Compared to the gold standard Sanger sequencing method, the Onycho+ test reported an agreement of 91.39%, a sensitivity of 100% and a specificity of 84.5% in detecting dermatophytes, superior to the histology method which had a 69.53% agreement, 85.1% sensitivity and 57.1% specificity. The distribution of fungal organisms detected in this cohort shows a dermatophyte majority but a higher-than-expected proportion of NDMs. Nails negative for the Onycho+ test and positive for histology were mostly NDMs. This study demonstrates that the clinical performance of the Onycho+ test is superior to histology in detecting dermatophytes and that a combination of Onycho+ and histology can result in a higher clinical accuracy.

In order to assess the knowledge and experience of fungal infections (FIs) among clinicians in Senegal, a cross-sectional survey was carried out among medical practitioners in Senegal via a questionnaire designed with “Google Forms” between 24 January and 24 April 2022. A total of 100 clinicians responded to the questionnaire. Clinicians in the 31– 40-year-old age group formed the majority of respondents (51%). Male respondents were predominant (72%). Forty-one percent of respondents were general practitioners, 40% were specialist doctors, and the rest were residents. Dermatologists were the most common at 15% (6/40). In terms of clinicians’ general knowledge of fungi, FIs and their therapeutic management, an average of 70% correct answers was recorded. The majority (70%) of respondents cared for between two to four different categories of patients at risk of invasive FIs (IFIs) at a time, with diabetes predominating. Eighty percent confirmed that they had been confronted with FIs, including 43% with superficial FIs, 3% with subcutaneous FIs and 5% with IFIs. Thirty-four percent of doctors stated that they had never suspected an IFI. Candidiasis was the most commonly mentioned mycosis by doctors. To support the diagnosis of these FIs, 22% of the clinicians said that they had recourse only to the clinical diagnosis. In total, 79% of clinicians responded that they had never used an antifungal chemoprophylaxis. In addition, 28% and 22% of practicing physicians chose a combination of antifungals for the chemoprophylaxis of invasive candidiasis and invasive aspergillosis, respectively. This survey shows that both clinicians’ knowledge and experience of fungi, antifungals, FIs and their therapeutic management, as well as chemoprophylaxis, need to be improved. Indeed, half of the clinicians seem to be unaware of the incidence of FIs, in particular IFIs, which, nevertheless, represent some of the deadliest infectious diseases in the world.

Although the treatment of aspergillosis has been studied for years, the optimal nonsurgical treatment of chronic cavitary pulmonary aspergillosis (CCPA) remains unsatisfactory, especially in lung cancer. We report two advanced non-small cell lung cancer (NSCLC) patients who recovered from CCPA following instillation of Amphotericin B (AmB) by bronchoscopy combined with systemic voriconazole. The first patient was diagnosed with lung adenocarcinoma after right upper lobe resection and was treated with anaplastic lymphoma kinase-targeted therapy. Chest computed tomography (CT) revealed a right pulmonary cavity containing solid materials. The second patient was diagnosed with squamous cell carcinoma and received immunotherapy following surgery, chemotherapy, and radiotherapy. Chest CT tomography revealed a mass in the right lung cavity. Both patients' cultures and next-generation sequencing of their bronchoalveolar lavage (BAL) samples revealed presence of Aspergillus fumigatus. In addition, the galactomannan test of both patients BAL samples was positive. Systemic voriconazole was prescribed based on in vitro susceptibility testing. The chest images and clinical symptoms of both patients did not improve after one month of voriconazole therapy within the therapeutic blood concentration. Considering the low local concentrations of antifungals against CCPA, AmB instillation by bronchoscopy combined with systemic voriconazole was utilized. The chest CT images and clinical symptoms of both patients markedly improved in the following third month. Instillation of AmB combined with systemic voriconazole may be a promising treatment option for NSCLC patients with CCPA who fail voriconazole monotherapy.

Trichophyton indotineae is a newly described dermatophyte species. This fungal pathogen has recently emerged in India and is responsible for chronic or recurrent widespread superficial infections. Resistance to terbinafine is frequently associated to this pathogen and is related to point mutations in the gene encoding the squalene epoxidase. T. indotineae infections have been reported outside India, highlighting the risk of worldwide diffusion of this microorganism. Species identification and antifungal susceptibility determination are key points for infection control but still remain challenging. Systemic treatment is usually required and itraconazole is frequently prescribed in case of terbinafine resistance. This review summarizes main features of T. indotineae taxonomy, epidemiology, clinical manifestations, identification, antifungal profile, treatment and prevention.