Journal de mycologie medicale最新文献

Trichophyton indotineae is an emerging dermatophyte that has remarkable impact on public health worldwide. In addition to producing severe extensive skin lesions, this species is frequently resistant to terbinafine, used as a first line agent. As a result, the infection is often refractory, making treatment very challenging. The current report describes the first case of Trichophyton indotineae infection in Kuwait. The infected woman had no recent travel history. She failed to respond to several courses of antifungals, but finally responded to voriconazole. The report suggests that T. indotineae is under recognised, hence, active surveillance of dermatophytes is warranted.

Fungal infections caused by Cryptococcus spp. pose a threat to health, especially in immunocompromised individuals. The available arsenal of drugs against cryptococcosis is limited, due to their toxicity and/or lack of accessibility in low-income countries, requiring more therapeutic alternatives. Selective serotonin reuptake inhibitors (SSRIs), through drug repositioning, are a promising alternative to broaden the range of new antifungals against Cryptococcus spp. This study evaluates the antifungal activity of three SSRIs, sertraline, paroxetine, and fluoxetine, against Cryptococcus spp. strains, as well as assesses their possible mechanism of action. Seven strains of Cryptococcus spp. were used. Sensitivity to SSRIs, fluconazole, and itraconazole was evaluated using the broth microdilution assay. The interactions resulting from combinations of SSRIs and azoles were investigated using the checkerboard assay. The possible action mechanism of SSRIs against Cryptococcus spp. was evaluated through flow cytometry assays. The SSRIs exhibited in vitro antifungal activity against Cryptococcus spp. strains, with minimum inhibitory concentrations ranging from 2 to 32 μg/mL, and had synergistic and additive interactions with azoles. The mechanism of action of SSRIs against Cryptococcus spp. involved damage to the mitochondrial membrane and increasing the production of reactive oxygen species, resulting in loss of cellular viability and apoptotic cell death. Fluoxetine also was able to cause significant damage to yeast DNA. These findings demonstrate the in vitro antifungal potential of SSRIs against Cryptococcus spp. strains.

Introduction

Pythiosis is a high-mortality infectious condition in humans and animals. The etiologic agent is Pythium insidiosum. Patients present with an ocular, vascular, cutaneous/subcutaneous, or gastrointestinal infection. Antifungal medication often fails to fight against P. insidiosum. The effective treatment is limited to radical surgery, resulting in organ loss. Fatal outcomes are observed in advanced cases. Pythiosis needs to be studied to discover novel methods for disease control. Genome data of P. insidiosum is publicly available. However, information on P. insidiosum biology and pathogenicity is still limited due to the lack of a cost-effective animal model and molecular tools.

Materials and methods

We aimed to develop a high-efficiency protocol for generating P. insidiosum protoplast, and used it to set up an animal model, in vitro drug susceptibility assay, and DNA transformation for this pathogen.

Results

P. insidiosum protoplast was successfully generated to establish a feasible pythiosis model in embryonic chicken eggs and an efficient in vitro drug susceptibility assay. DNA transformation is a critical method for gene manipulation necessary for functional genetic studies in pathogens. Attempts to establish a DNA transformation method for P. insidiosum using protoplast were partly successful. Significant work needs to be done for genetically engineering a more robust selection marker to generate stable transformants at increased efficiency.

Conclusion

This study is the first to report an efficient P. insidiosum protoplast production for clinical and research applications. Such advances are crucial to speeding up the pathogen's biology and pathogenicity exploration.

Objectives

Cyberlindnera fabianii is an opportunistic pathogen isolated from clinical specimens. It can be incorrectly identified as Candida utulis by phenotypic methods. This study aimed to accurately identify Cy.fabianii strains isolated from the urinary tract, and to determine their molecular characterization and antifungal susceptibilities as well.

Methods

Twenty-nine yeast strains isolated from urinary tract samples were studied. Strains were identified by phenotypically, sequence analysis and MALDI-TOF MS. Sequence analysis using different gene regions (ITS1-2,D1/D2,EF-1-alpha) in ribosomal DNA was performed for the molecular analysis. Phylogenetic analysis was done by the neighbor-joining method. Antifungal susceptibilities of strains were determined for nine antifungals by reference broth microdilution and the Sensititre YeastOne broth microdilution method (Sensititre^TMYeastOne^TMAST Plate, Thermo Fisher Scientific™,USA) according to CLSI M60-Ed2 recommendations.

Results

All strains were identified as C.utulis phenotypically by conventional methods, however all strains were identified as Cy.fabianii by sequence analysis and MALDI-TOF MS. It was observed that the gene regions examined in terms of determining evolutionary relatedness did not show intraspecies nucleotide variations. In all strains, the MIC50/MIC90 values for fluconazole were higher than the other antifungals tested.

Conclusion

Cy.fabianii should be considered in fluconazole-resistant urinary tract yeast infections. Although conventional phenotypical methods were insufficient to identify Cy.fabianii, it could be correctly identified with sequence analysis using different gene regions (ITS1-2,D1/D2,EF-1-alpha) in ribosomal DNA and MALDI-TOF MS.

Introduction

Here we tested the correlation between minimum inhibitory concentrations (MICs) of major antifungal agents and sequence types (STs) within Cryptococcus neoformans VNI isolates, and explored the ERG11 gene of included strains.

Materials and methods

We analysed 23 C. neoformans strains categorised into two groups according to the distribution of the ST profile in Kinshasa clinics (Democratic Republic of Congo): major ST [ST93 (n = 15)], and less common STs [ST659 (n = 2), ST5 (n = 2), ST4 (n = 1), ST 53 (n = 1), ST31 (n = 1), and ST69 (n = 1)]. The MICs of the major antifungal agents [amphotericin B (AMB), 5-fluorocytosine (5FC) and fluconazole (FCZ)] were determined following EUCAST guidelines. ERG11 gene sequences were extracted from whole genome sequence of the isolates and compared with the wild-type gene sequence of the C. neoformans VNI.

Results

Although major ST isolates appeared to have lower median MICs for AMB and 5FU than less common ST isolates (0.50 vs. 0.75 mg/L for AMB, 2 vs. 4 mg/L for 5FU, respectively), FCZ susceptibility was similar in both groups (4 mg/L) (p-value >0.05). The susceptibility profile of C. neoformans strains separately considered did not significantly affect the patients’ clinical outcomes (p-value >0.05). Furthermore, two structural modalities of the ERG11 gene were observed: (1) that of the reference gene, and (2) that containing two exonic silent point substitutions, and one intronic point substitution located in a sequence potentially involved in pre-mRNA splicing (c.337-22C > T); with no association with the MICs of the isolates (p-value >0.05).

Conclusions

The lack of association/correlation found in this study calls for further investigations to better understand the mechanisms of C. neoformans resistance to antifungal agents.

Lomentospora prolificans is an opportunistic pathogen that can cause invasive lomentosporiosis in immunocompromised patients. Patients with hematological malignancies and those who have undergone stem cell or solid organ transplantations are in the highest risk group. In addition to the limitations and delays in diagnostic possibilities, L. prolificans has a high mortality due to its resistance to all available antifungal drugs. In a patient diagnosed with aplastic anemia, we described the first case of L. prolificans in Türkiye. L. prolificans was identified in the blood culture, and despite the initiation of antifungal treatments, the fungemia resulted in mortality on the 7th day of intensive care hospitalization. This case highlights the importance of early recognition and prompt initiation of appropriate antifungal therapy to improve the outcome of patients with rare mold infections.

Aims

The rare yeast species Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii, and Wickerhamomyces anomalus are increasingly implicated in severe mycoses in immunocompromised patients. This study aimed to assess the prevalence of uncommon yeast species in Côte d'Ivoire.

Methods

The yeast isolates from superficial samples, mainly vaginal swabs, were collected at the Pasteur Institute of Abidjan in a study on the molecular epidemiology of clinical yeast species. Identification relied on MALDI-TOF MS and ITS sequence analysis. Antifungal susceptibility testing was performed using the CLSI method.

Results

Of the 315 strains analysed from 227 outpatients, 14 belonged to 4 uncommon species: Lodderomyces elongisporus, Kodamaea ohmeri, Cyberlindnera fabianii, and Wickerhamomyces anomalus. None exhibited elevated fluconazole, amphotericin B, caspofungin, ketoconazole, or flucytosin MIC.

Conclusions

The presence of these rare yeasts represents a risk in immunocompromised people. Their adequate and timely identification is a priority. Overall, enhancing the mycoses diagnostic capacities in Côte d'Ivoire, and more generally in African clinical laboratories with limited resources is a critical aim.

Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has been approved for various hematological malignancies. Invasive aspergillosis is a known complication of ibrutinib, but mucormycosis is rare. We describe the case of a 70-year-old man with mantle cell lymphoma infiltrating the trachea, managed with a tracheobronchial stent and ibrutinib. He had improved one month after treatment, and we removed the airway stent. Four months later, he developed tracheal nodules confirmed to be tracheal mucormycosis and responded to liposomal amphotericin B (3.5 g) followed by posaconazole. After transient improvement, the tracheal lesions recurred, the biopsy showed lymphoma (with no evidence of mucormycosis), and he died. A systematic review of the literature identified 20 additional cases of ibrutinib-associated mucormycosis. Most of the 21 patients included were men (95%), and ibrutinib was the only risk factor in 15.7%. The reported mortality was 31.6% (6/19), attributable to mucormycosis in half the cases.

An unprecedented mucormycosis outbreak occurred in India during the second COVID-19 wave in spring 2021. COVID-19-associated mucormycosis (CAM) was observed, mainly rhino-orbito-cerebral mucormycosis (ROCM), in patients with poorly controlled diabetes and treated with inappropriate doses of glucocorticoids. The aim of this mini-review was to compare the characteristics of the CAM epidemic in India with (i) mucormycosis cases before the COVID-19 pandemic and (ii) CAM in the rest of the world (particularly in France) in order to identify the reasons for this outbreak. In India, the major mucormycosis epidemiologic change during the COVID-19 pandemic was an increase in the percentage of patients treated with corticosteroids who developed CAM. Compared with the rest of the world, India reported a higher mucormycosis incidence even before the COVID-19 pandemic. Moreover, in India, patients with CAM were more likely to have diabetes mellitus and ROCM; conversely, mortality rates were lower. The reasons for such a localized epidemic in India have remained unclear, but some hypotheses can be put forward, particularly the combination of high prevalence of uncontrolled diabetes mellitus and frequent indiscriminate corticosteroid utilization in a country that already had a high mucormycosis burden before the COVID-19 pandemic.