Mycoses最新文献

Background: Invasive candidiasis (IC) represents a significant threat to both mortality and morbidity, especially among vulnerable populations. Intra-abdominal candidiasis (IAC) frequently occurs in critically ill and cancer patients, with these specific groups carrying a heightened risk for such invasive fungal infections. Despite this, there is a noticeable lack of attention to IAC in cancer patients within the literature, highlighting a critical gap that requires urgent consideration.

Objectives: This study aimed to explore the clinical and epidemiological characteristics of IAC and identify prognostic factors in a cancer centre in a middle-income country over 10 years.

Patients/methods: A retrospective cohort observational study of adults diagnosed with IAC was conducted at the Instituto do Cancer do Estado de São Paulo (ICESP), a tertiary hospital specialising in oncological diseases with 499 beds, including 85 intensive care unit (ICU) beds, from December 2009 through May 2021.

Results: A total of 128 episodes were included: 67.2% admitted to the ICU; 54.7% males; and median age 62 years. The predominant diagnosis was peritonitis (75.8%). Blood culture samples were collected from 128 patients upon admission, revealing candidemia in 17.2% (22). The most frequently isolated were C. albicans (n = 65, 50.8%) and C. glabrata (n = 42, 32.8%). Antifungal treatment was administered to 91 (71%) patients, with fluconazole (64.8%) and echinocandins (23.4%) being the most common choices. A significant proportion of these patients had a history of abdominal surgery or antibiotic use. Independent factors associated with 30-day mortality included the median Sequential Organ Failure Assessment (SOFA) score of 6 (OR = 1.30, 95% CI 1.094-1.562, p = 0.003), days of treatment (median 10.5) (OR = 0.93, 95% CI 0.870-0.993, p = 0.031) and abdominal source control (78.1%) (OR = 0.148, 95% CI 0.030-0.719, p = 0.018). The 30-day mortality rate was 41.1%.

Conclusions: Our study underscores the critical importance of implementing effective source control as a key strategy for reducing mortality in IAC.

Background: Invasive fungal disease (IFD) is a sinister complication encountered in patients with haematological disorders. When occurring in the central nervous system (CNS), IFDs can have catastrophic outcomes.

Objectives: To study the clinical presentation, predisposing etiological factors, and prognosis of a CNS-IFD in a patient with a haematological disorder.

Patients and methods: This is a retrospective study focusing on the clinical profile, diagnosis, treatment strategy and outcomes of 43 patients with an underlying haematological disorder, who were diagnosed with CNS-IFD between 2018 and 2022.

Results: Of the 43 patients, 18 were chemotherapy recipients, while 23 were stem cell transplant (SCT) recipients and 2 presented with CNS-IFD at diagnosis. AML/MDS (37.2%) and ALL (18.6%) were the predominant underlying diagnoses. A sudden deterioration in sensorium (53.5%) was the earliest clinical sign, while T2 hyperintensities (26.8%), vascular involvement (26.8%) and ring-enhancing lesions (16.3%) were the commonest radiological findings, with all patients exhibiting diffusion restriction in diffusion-weighted images. Microbiological evidence of infection was obtained in all patients; however, culture positivity was established in only 25 patients. Rhizopus spp (23.2%) and Aspergillus spp (20.9%) were implicated in most cases. Overall survival of the cohort was 27.9% at a median follow-up of 6 months. In patients who succumbed, the median time to death was 4 days (0-46).

Conclusion: CNS-IFD is associated with very poor survival in patients undergoing chemotherapy or an SCT, urging the need for prompt diagnosis and initiation of suitable antifungal therapy.

Exophiala dermatitidis is an emerging black fungus that causes pulmonary infections that may be underestimated by conventional culture methods. We encountered one case that initially appeared to be yeast and was misidentified as Rhodotorula spp. using a commercial identification kit. Thus, genetic identification and clinical background investigations were conducted on 46 strains of Rhodotorula spp. The sequences of the internal transcribed spacer and large-subunit RNA genes (D1/D2 regions) of 43 isolates, excluding two environmental isolates and one difficult-to-culture isolate, were determined and genetically identified. Notably, 22 isolates were identified as E. dermatitidis and misidentified as Rhodotorula spp. using the conventional method. Based on the exclusion criteria, the clinical information of 11 patients was retrospectively reviewed. Five cases (definite) had definite exacerbation of pulmonary infections due to E. dermatitidis, and six cases (possible) had undeniable infections. Of the 11 cases of pulmonary infection suggested to be caused by E. dermatitidis, comorbidities included two cases of chronic pulmonary aspergillosis (CPA), three cases of pulmonary non-tuberculous mycobacterial (NTM) infection and one case of pulmonary nocardiosis, suggesting a trend towards simultaneous detection of chronic pulmonary infections. Steroid and immunosuppressive drug use was observed in five cases, and β-D-glucan elevation was observed in three of five definite cases of pulmonary infections due to E. dermatitidis. The possibility of E. dermatitidis infection should be considered when Rhodotorula spp. are isolated from cultures of airway-derived specimens, and, in addition to CPA and NTM, identification of E. dermatitidis may be important in chronic pulmonary infections.

Background: Tinea capitis is an infectious dermatosis frequent in children, causative fungi variable over time and space. The risk factors associated with this disease are still poorly understood. The objective of this study was to estimate the prevalence of tinea capitis among schoolchildren in Lomé (Togo), identify the fungal species involved and assess the associated risk factors.

Patients and methods: It was a cross-sectional and case-control study conducted in primary schools in Lomé from November 2020 to April 2021. All pupils presenting tinea capitis suspected lesions have been sampled, and the scraping and hair were examined by direct microscopy in KOH solution and cultured in Sabouraud dextrose agar with chloramphenicol and cycloheximide. Positive children were matched by age and sex with those without symptoms for case-control study.

Results: Out of the 15,087 pupils enrolled, 465 had positive cultures for dermatophytes, corresponding to the tinea capitis prevalence of 3.08% (95% CI [2.59-3.57]). Trichophyton mentagrophytes (81.86%) and Trichophyton soudanense (13.12%) were the majors isolated dermatophytes. The risk factors were mostly living in households with domestic animals, showering less than twice a day, having a history of ringworm, having similar lesions in the same household and sharing personal hygiene items.

Conclusion: This study highlights the low prevalence of tinea capitis in schoolchildren in Lomé (Togo), the causative species dominated by T. mentagrophytes and emphasises the importance of environmental and behavioural factors in the mycosis transmission. Implementing preventive measures addressing the identified factors could help to reduce the prevalence of this disease.

Background: Terbinafine is widely used to treat onychomycosis caused by dermatophyte fungi. Terbinafine resistance in recent years is causing concern. Resistance has so far been associated with single-nucleotide substitutions in the DNA sequence of the enzyme squalene epoxidase (SQLE) but how this affects SQLE functionality is not understood.

Objectives: The aim of this study was to understand newly discovered resistance in two Australian strains of Trichophyton interdigitale.

Patients/methods: Resistance to terbinafine was tested in four newly isolated strains. Three-dimensional SQLE models were prepared to investigate how the structure of their SQLE affected the binding of terbinafine.

Results: This study found the first Australian occurrences of terbinafine resistance in two T. interdigitale strains. Both strains had novel deletion mutations in erg1 and frameshifts during translation. Three-dimensional models had smaller SQLE proteins and open reading frames as well as fewer C-terminal α-helices than susceptible strains. In susceptible strains, the lipophilic tail of terbinafine was predicted to dock stably into a hydrophobic pocket in SQLE lined by over 20 hydrophobic amino acids. In resistant strains, molecular dynamics simulations showed that terbinafine docking was unstable and so terbinafine did not block squalene metabolism and ultimately ergosterol production. The resistant reference strain ATCC MYA-4438 T. rubrum showed a single erg1 mutation that resulted in frameshift during translation, leading to C-terminal helix deletion.

Conclusions: Modelling their effects on their SQLE proteins will aid in the design of potential new treatments for these novel resistant strains, which pose clinical problems in treating dermatophyte infections with terbinafine.

Introduction: Equal access to medicines is crucial to ensuring public health, but access is difficult to measure, especially for infections where changes in infective species make treatment choices highly dynamic. This study investigated if the combination of infection prevalence with medicine efficacy and regulatory availability could access medicines access of topical onychomycosis medicines.

Methods: Two databases, PubMed and Web of Science, were used to identify relevant information published between 1990 and 2019. For the meta-analysis, human onychomycosis investigations using PCR analysis were included. Reviewers independently selected eligible articles, extracted data and assessed the study quality. A random-effects meta-analysis model with a Freeman-Tukey transformation was employed to the PCR data. For the meta-analysis, the global infection trends and regional differences in the infective organisms were determined.

Results: Of the 26 studies analysed, the PCR analysis in 18 studies confirmed onychomycosis in about half of the visually suspected cases (55%, CI 43%-67%). Across all 26 studies dermatophytes were the most prevalent infective organism (57%, CI 37%-76%), but a sub-group analysis showed yeasts predominated in females (31%, CI 0%-84%) (p < 0.0001), in fingernail infections (42%, CI 21%-65%) (p < 0.0001) and in arid countries (p < 0.0001). Combining these results with medicine efficacy data showed that residents from 83 of the 92 countries assessed (90%) could not access the most efficacious topical product, and 22% could not access any broad-spectrum agents. Countries in Africa had the poorest access to topical onychomycosis medicines.

Conclusion: This study identified that access to effective topical products for onychomycosis is a global problem. This issue appeared to be due to under-representation of candida infections in pivotal clinical studies of topical onychomycosis products. A head-to-head multicentre study for topical efinaconazole or a novel broad spectrum topical agent is needed to help resolve these access problems.

Protocol registration: PROSPERO-CRD42023464744.

Background: Mucormycosis is a rare but critical infection. Due to its rarity, there is scarce evidence about the longitudinal changes in the epidemiology of mucormycosis in the US.

Objectives: We investigated the longitudinal epidemiology, detailed clinical characteristics, treatment and outcomes of patients with mucormycosis within the US Veterans Health Administration (VHA) over 20-year period.

Patients/methods: All adult patients who were admitted to an acute-care hospital with a diagnosis of mucormycosis within the VHA from January 2003 to December 2022.

Results: Our study included 201 patients from 68 hospitals. Incidence rates of mucormycosis increased from 1.9 per 100,000 hospitalisations in 2003 to 3.3 per 100,000 hospitalisations in 2022, with a peak incidence at 5.9 per 100,000 hospitalisations in 2021, when the Delta wave of COVID-19 hit the US. Rhino-orbital (37.3%) and pulmonary mucormycosis (36.8%) were the most common types of infection. Diabetes mellitus (59.1%) and leukaemia (28.9%) were most common comorbidities predisposing to mucormycosis. Use of posaconazole or isavuconazole increased over time. The 90-day and 1-year mortalities were 35.3% and 49.8%, respectively. The mortality was lower in more recent years (2013-2017, 2018-2022) compared to earlier years (2003-2007). Age ≥65 (adjusted odds ratio [aOR]: 3.47, 95% CI 1.59-7.40), leukaemia as a comorbidity (aOR: 2.66, 95% CI 1.22-5.89) and central nervous system infection (aOR: 10.59, 95% CI 2.81-44.57) were significantly associated with higher 90-day mortality.

Conclusions: Our longitudinal cohort study suggests the increasing incidence rates but lower mortality of mucormycosis over this 20-year period.

Background: Onychomycosis (OM) is a common nail infection treated with amorolfine hydrochloride nail lacquer in China. Monitoring drug concentrations and using dermoscopy to evaluate treatment efficacy may provide new insights.

Objective: The study aims to analyse amorolfine concentrations in nails with mild to moderate OM, assess treatment outcomes using dermoscopy and explore factors influencing drug concentrations and efficacy.

Methods: Patients with mild to moderate OM confirmed by fungal microscopy were enrolled. Amorolfine nail lacquer was applied twice weekly for 36 weeks. Monthly nail samples measured amorolfine concentrations using liquid chromatography. Dermoscopy was performed before and after treatment to evaluate responses. Mixed-effects models and logistic regression analysed factors affecting drug concentrations and outcomes.

Results: Ninety-seven nails were included. Amorolfine concentrations increased over time, with higher levels in females, fingernails, 2nd-5th digits and superficial white OM (p < 0.05). Age was a risk factor, while drug concentration and OM type were protective for clinical efficacy (p < 0.05). Peak concentration correlated with clinical (r = 0.487, p = 0.000) and mycological (r = 0.433, p = 0.000) responses. Dermoscopic features improved significantly in successful cases (p < 0.05).

Limitations: In the assessment of fungal efficacy, only fungal microscopy was used, and fungal cultures were not performed. The study was limited by a small sample size and the lack of a longer follow-up to assess relapse.

Conclusion: Amorolfine concentrations vary with patient and nail characteristics, influencing efficacy. Dermoscopy is valuable for monitoring OM treatment.

Background: Blastomycosis is a pulmonary disease caused by Blastomyces spp., a group of pathogenic dimorphic fungi endemic to a number of geographic regions, specifically Manitoba and northwestern Ontario, Canada. Immunosuppression is a major risk factor affecting disease susceptibility, yet host immunity is not well understood. Genetic immunodeficiencies can also influence disease, with variants in IL6, GATA2 and VDBP shown to influence susceptibility. Additional genetic factors in disease susceptibility and severity remain undetected. Our study seeks to identify potential genetic risk factors in a blastomycosis case-control cohort from Manitoba and northwestern Ontario, Canada.

Methods: Exomes from 18 blastomycosis cases and 9 controls were sequenced, variants were identified and filtered for accuracy and quality. We performed candidate gene prioritisation and variant aggregation to identify genetic associations and explored the full exome dataset.

Results: Ninety-nine genetic variants in 42 candidate genes were identified in the exome dataset. No variants associated with susceptibility were identified in a single-variant analysis although two non-synonymous variants in TYK2 were enriched among cases suggesting a possible role in susceptibility. Gene-based association analysis found variants in TLR1 enriched in controls (p = 0.024) suggesting a possible protective effect. Gene cluster analysis identified genetic variants in genes of chromatin remodelling, proteasome and intraflagellar transport significantly enriched in cases (false discovery rates < 14%).

Conclusions: The findings in this study show novel associations with blastomycosis susceptibility. A better understanding of host immunity and genetic predisposition to Blastomyces infection can help to inform clinical practice for improved outcomes.