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Background: Fungal skin diseases are a significant burden in Asia, with varying trends from 1990 to 2019, highlighting the need for targeted interventions.

Objective: To investigate long-term trends in the incidence, prevalence and disability-adjusted life-year rates for fungal skin diseases in China, India, Japan and Singapore from 1990 to 2019.

Patients/methods: Data were obtained from the 2019 Global Burden of Disease Study. Independent age, period and cohort effects were calculated using age-period-cohort analysis.

Results: Age-standardised incidence, prevalence and disability-adjusted life-year rates of fungal skin diseases in China, India, Japan and Singapore decreased from 1990 to 2019. India has the highest standardised incidence, prevalence and disability-adjusted life-year rates. The crude incidence, prevalence and disability-adjusted life-year rates showed an increasing trend in China, Japan and Singapore, and a decreasing trend in India. The age-period-cohort analysis found that the age effect increased in China, Japan and Singapore at ages 45-94 years, and India showed higher risk coefficients at ages 5-20 and 45-94 years. The period effect increased in the four countries, with more pronounced increases in Japan and Singapore. The cohort effect showed a monotonic decline with birth cohort in the four countries, with a slightly slower decline in India.

Conclusion: Fungal skin diseases pose a serious burden in Asian countries. We recommend raising awareness and providing specialised interventions for fungal skin diseases, especially for high-risk groups, such as middle-aged and older adults aged ≤ 45 years and young Indians aged ≤ 20 years.

Background: Recurrent vulvovaginal candidosis (RVVC) has been associated with increased antifungal resistance. Recently, we reported that Candida isolates from Colombian patients with RVVC did not show an increase in antifungal resistance.

Objective: The aim of this study was to evaluate the virulence of Candida isolates from patients with RVVC.

Methods: A total of 40 Candida isolates were evaluated (37 C. albicans and 3 C. lusitaniae ). C. albicans isolates were divided into two groups based on the number of VVC episodes in patients per year: Group 1 (four to seven episodes; n = 26) and Group 2 (≥ eight episodes; n = 11). The XTT assay was used to assess biofilm formation. Galleria mellonella larvae were used for survival analysis and fungal load assessment, and the qPCR technique to determine the expression of the PRA1 gene.

Results: It was observed that C. lusitaniae and C. albicans isolates from patients with ≥ eight VVC episodes per year exhibited a greater capacity to form biofilms compared to those from patients with four to seven VVC episodes. Moreover, in the G. mellonella model, larvae inoculated with isolates from RVVC patients exhibited approximately 80% mortality. Similarly, larvae infected with C. albicans from patients who experienced ≥ eight VVC episodes showed a significantly higher fungal load compared to the other evaluated groups; likewise, the expression of the PRA1 gene was significantly higher in isolates from patients with ≥ eight VVC episodes.

Conclusion: These results indicate that Candida isolates from patients with RVVC exhibit a high degree of virulence and suggest that virulence may be one of the mechanisms explaining recurrence rather than antifungal resistance itself.

Background: Available data on combat wound-related invasive mould infections (IMIs) are limited.

Objectives: We aimed to describe the characteristics and outcomes of IMIs in casualties of a recent conflict.

Patients/methods: A retrospective study including hospitalised patients with combat-related injuries, fulfilling criteria for wound-related IMI based on Trauma Infectious Disease Outcomes Study definitions. Patient and injury characteristics, management and outcomes are described and compared to previous cohorts. Mould isolates and susceptibility testing results, including the novel agent manogepix, are reported.

Results: Overall, 31 patients (69 mould isolates) were included-resulting in an IMI incidence rate of 1.9%. Blast was the most common injury mechanism (71%), with limb amputations and abdominoperineal injuries in 35% and 45%, respectively. Mould cultures, obtained mostly from lower extremities wounds (62%), were positive in all patients. Most (68%) had poly-mould infections, with Aspergillus and Fusarium species predominating. Overall, non-susceptibility rates of > 50% to newer azoles and 38% to amphotericin B reflected the high proportion of Fusarium spp., A. terreus and A. flavus, with the lowest azole minimal inhibitory concentrations demonstrated with posaconazole. Manogepix displayed good in-vitro activity against all isolates, except for Mucorales species. Two patients (6.5%) died of disseminated IMIs and 19% required amputations. Patients with Mucorales had poorer outcomes (40% mortality/amputation vs. 19% for non-Mucorales).

Conclusions: Combat wound-related IMIs are uncommon but carry significant morbidity and mortality. High susceptibility rates to manogepix were observed. Further studies are needed to evaluate optimal surgical approaches and the role of antifungal susceptibility testing in this setting.

Background: Obtaining non-directed samples from the upper bronchial tree is easier to perform and poses fewer risks for critically ill patients than deep bronchoalveolar lavage (BAL). Since invasive pulmonary aspergillosis is associated with a high mortality in critically ill patients, timely diagnosis and rapid initiation of treatment are of utmost importance.

Objectives: The objective of this study was to compare Galactomannan (GM) testing by Enzyme Immunoassay (EIA), GM Lateral Flow Assay (LFA) and the detection of Aspergillus DNA by Polymerase Chain Reaction (PCR) between directed BAL and non-directed bronchial lavage (BL) in critically ill patients.

Methods: In this prospective, exploratory pilot study, we analysed 120 samples from 40 patients admitted to 12 mixed intensive care units. Inclusion criteria required either risk factors for IPA or positive Aspergillus assessments and met the criteria published by the European Society of Clinical Microbiology and Infectious Diseases guidelines for IPA diagnosis. Both respiratory secretions and blood were collected. In each patient, LFA and PCR were performed on BAL, BL and blood serum, respectively. The EIA test was applied to the BL and BAL of each patient, and the serum of 24 patients. The study was registered on clinicaltrials.gov (NCT04848831).

Results: In a total of 80 respiratory samples, Aspergillus GM EIA yielded optical density indices (ODI) ranging from 0.04 to ≥ 3.5. We observed a high correlation between BAL and BL samples for Aspergillus GM EIA (Pearson's r = 0.78 [95% CI 0.62, 0.88]; intraclass correlation coefficient 0.78). At an ODI cutoff of 0.8 for BAL and 1.2 for BL, the sensitivity of Aspergillus GM EIA was 0.94, while the specificity was 0.67. Increasing the BAL cutoff to 1.0 ODI improved the specificity to 0.86. Aspergillus PCR examination showed good agreement between the two compartments, with a Cohen's kappa coefficient of 0.75 (95% CI 0.48, 1.00). The correlation of Aspergillus GM LFA between BAL and BL was weak.

Conclusions: Our findings demonstrate that the detection of Aspergillus GM using EIA or Aspergillus PCR in BL is comparable to that in BAL. Thus, BL samples can be reliably used for diagnosing invasive pulmonary aspergillosis.

Introduction: Although there are some studies evaluating CIE incidence and associated risk factors, none assessed mortality several months after the Candida spp. BSI episode. We aimed to assess risk factors for CIE and outcomes, including 1-year mortality, in patients with Candida spp. BSI in a public tertiary-care teaching hospital in Brazil.

Patients and methods: Retrospective case-control, followed by a cohort study, with adult patients who presented a Candida spp. BSI. Participants were eligible if they had at least one echocardiogram performed no longer than 3 days before Candida spp. BSI diagnosis and thereafter during the respective hospital admission. CIE diagnosis was defined by the presence of two major Duke criteria.

Results: We studied 164 patients (median age: 57.6 years) with a median Charlson comorbidity index of 3 points. Most patients were female (54.9%), were on haemodialysis (54.9%), and 4.6% had a preexisting moderate/severe heart valve disease. C. albicans (36.2%) and C. parapsilosis complex (34.4%) were the most frequent Candida species identified. CIE was detected in 10 patients (6.1%; 95% CI: 2.4%-9.8%). In the multivariable analysis, age and C. parapsilosis complex remained as independent predictors of CIE. There was no significant difference between CIE and no CIE groups in 1-year mortality after Candida spp. BSI diagnosis and hospital discharge.

Discussion: Considering the low costs and hazards associated with an echocardiogram, performing it systematically in all patients with Candida spp. BSI might improve CIE diagnosis and ultimately survival rates.

Background: Emerging terbinafine resistance in Trichophyton species has been reported globally. The prevalence in clinical samples from patients with treatment failure is unknown in Denmark.

Objectives: Prospective study of terbinafine resistance in Trichophyton isolates from patients with recalcitrant skin or nail infections.

Patients/methods: Clinical samples (nails or skin scrapings) from patients with recalcitrant infections were included. Isolates were tested with the EUCAST broth microdilution method, E.Def 11.0 and DermaGenius Resistance Multiplex PCR kit (PathoNostics, The Netherlands).

Results: Thirty-three isolates were included in the study, 27 (81.8%) T. rubrum, 2 (6.1%) T. interdigitale, 1 (3.0%) T. mentagrophytes and 3 (9.1%) T. indotineae. Sixteen of 31 isolates (52%) were terbinafine resistant with the EUCAST broth microdilution method, 13 T. rubrum and 3 T. indotineae. Two isolates did not grow in the broth culture medium. The DermaGenius Resistance Multiplex PCR kit showed mutations associated with terbinafine resistance in 11 isolates. All of the 11 isolates with detected mutations by PCR also displayed terbinafine resistance by the EUCAST method.

Conclusions: Terbinafine resistance was detected in 52% of Trichophyton isolates from recalcitrant infections by the EUCAST broth microdilution. T. rubrum was the most common species among the resistant isolates (81.3%). The DermaGenius Resistance Multiplex PCR kit was a reliable tool for the detection of mutations associated with terbinafine resistance and is suitable as an initial screening for terbinafine resistance before results from EUCAST broth microdilution testing is available. Susceptibility testing of Trichophyton spp. from skin and nail samples is highly relevant from patients with terbinafine treatment failure.

Objective: The global prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) has been steadily increasing. A few small retrospective studies have reported a poor prognosis associated with chronic pulmonary aspergillosis (CPA) as a complication of NTM-PD. Furthermore, the prognostic impact of CPA may have been inadequately assessed due to differences in background factors. This study aimed to identify the risk factors for CPA in NTM-PD and compare the risk of in-hospital mortality between patients with and without aspergillosis.

Methods: Data were obtained from a large-scale claims database. Patients with NTM-PD who met the inclusion criteria and those who developed CPA after the NTM diagnosis were identified. The incidence of CPA was evaluated, and risk factors were identified using multiple logistic analyses. Mortality rates were evaluated and compared between patients with and without aspergillosis after adjusting for background CPA risk factors.

Results: The incidence of CPA was 2.29% (265/11,587). The identified risk factors included male sex, chronic respiratory failure, asthma, interstitial pneumonia, pulmonary tuberculosis sequelae and systemic corticosteroid use. A total of 219 patients with CPA were matched with control cases using propensity scores based on age and identified risk factors for CPA. The adjusted hazard ratio for in-hospital mortality was 2.6 (95% CI: 1.8-3.9).

Conclusions: CPA as a complication of NTM-PD is associated with significantly higher mortality rates. Clinicians should consider the necessity of promptly diagnosing CPA in patients with NTM-PD and the associated risk factors.

Background: Since 2017, dermatophytosis caused by the newly introduced species Trichophyton indotineae has gained new interest worldwide due to the rise in terbinafine resistance and difficulty in the treatment of recalcitrant infections. Distinguishing T. indotineae from other Trichophyton species based on morphological features is impossible and DNA sequencing is necessary for accurate identification. Though early identification of the species is not solely sufficient for the treatment of infected cases, it is important for clinicians to take the next appropriate modalities such as antifungal susceptibility testing especially when the patients have extensive skin lesions recalcitrant to therapy by terbinafine. Here, we developed a rapid diagnostic scheme using SYBR Green real-time PCR for the specific detection/identification of T. indotineae.

Methods: DNA was extracted from 397 dermatophyte isolates and two SYBR Green real-time PCR assays targeting the C120-287 and E054-58 intergenic loci were developed. Using a collection of 132 T. indotineae and 128 non-T. indotineae strains, all had already been identified by ITS-PCR-sequencing and 137 unknown dermatophyte isolates, the assays were evaluated.

Results: In both real-time PCR assays, 130 out of 132 T. indotineae strains were positive while all non-T. indotineae species were negative. Among 137 unknown tested isolates, 72 were identified as T. indotineae based on two real-time PCR assays, while 65 showed no peak and were considered non-T. indotineae. Based on PCR-sequencing as the reference standard, the SYBR Green real-time PCR assays demonstrated a sensitivity of 98.48% and a specificity of 100%.

Conclusion: The developed diagnostic assays using SYBR Green real-time PCR provided a rapid and accurate method for the distinction of cultured T. indotineae isolates and can be considered to evaluate for the detection of T. indotineae directly from clinical samples.

Background: This study investigated the impact of posaconazole (POSA) prophylaxis in COVID-19 patients with acute respiratory failure receiving systemic corticosteroids on the risk for the development of COVID-19-associated pulmonary aspergillosis (CAPA).

Methods: The primary aim of this prospective, multicentre, case-control study was to assess whether application of POSA prophylaxis in mechanically ventilated COVID-19 patients reduces the risk for CAPA development. All consecutive patients from centre 1 (cases) who received POSA prophylaxis as standard-of-care were matched to one subject from centre 2 and centre 3 who did not receive any antifungal prophylaxis, using propensity score matching for the following variables: (i) age, (ii) sex, (iii) treatment with tocilizumab and (iv) time at risk.

Results: Eighty-three consecutive patients receiving POSA prophylaxis were identified at centre 1 and matched to 166 controls. In the matched cohort, incidence rates of CAPA were 1.69 (centre 1), 0.84 (centre 2) and 7.18 (centre 3) events per 1000 ICU days. In multivariable logistic regression analysis, the presence of an EORTC/MSGERC risk factor at ICU admission (OR 4.35) and centre 3 versus centre 1 (OR 6.07; 95% CI 1.76-20.91; p = 0.004) were associated with an increased risk of CAPA. No increased risk of CAPA was registered for centre 2 versus centre 1.

Conclusions: The impact of POSA prophylaxis depends on the baseline CAPA incidence rate, which varies widely between centres. Future trials should therefore investigate targeted antifungal prophylaxis (e.g., stratified for high-prevalence centres or high-risk patients) in COVID-19 patients.

Trial registration: NCT05065658.

Background: The airways of patients with cystic fibrosis (pwCF) harbour complex fungal and bacterial microbiota involved in pulmonary exacerbations (PEx) and requiring antimicrobial treatment. Descriptive studies analysing bacterial and fungal microbiota concomitantly are scarce, especially using both culture and high-throughput-sequencing (HTS).

Objectives: We analysed bacterial-fungal microbiota and inter-kingdom correlations in two French CF centres according to clinical parameters and antimicrobial choices.

Methods: Forty-eight pwCF with PEx from Creteil (n = 24) and Lille (n = 24) CF centres were included over 2 years. Sputa were collected for culture and targeted-HTS (ITS2 and V3-V4 targets). Sequencing and culture data, along with clinical, radiological and treatment data, were analysed. Two-level stratified analysis was performed to study potential confounding factors (age, CF mutation, FEV1 and antibiotics) on the centre factor. Inter-kingdom correlations were analysed.

Results: Significant differences in the bacterial microbiota profile were found between centres (p-value = 0.03). For mycobiota, the taxonomic distribution and diversity were comparable. HTS provided concordant but more detailed information than culture and increased detection of main CF fungi (> 25% more positive samples for Aspergillus or Scedosporium). FEV1 and systemic antibiotic before PEx influenced bacterial microbiota, but no clinical association was found with the mycobiota. No inter-kingdom correlation between Pseudomonas and fungi was found.

Conclusions: Describing concomitant bacterial and fungal communities of pwCF at the beginning of PEx using culture and HTS shows greater diversity in HTS and better detection in case of low microbial load. Interesting inter-kingdom correlations were observed, requiring further research on larger cohorts to understand the potential microbial interactions.