Mycoses最新文献

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.

Background: Trichophyton benhamiae is a common dermatophyte whose natural host is the guinea pig and which causes highly inflammatory skin lesions in humans. The subtilisin 6 (SUB6) of this fungus belongs to a family of 12 SUB genes. Its encoding gene, overexpressed in vivo but not in vitro, has been considered a potentially important virulence factor, but its role in pathogenesis remains to be elucidated.

Objectives: The aim of this study was to assess the role of T. benhamiae SUB6 in virulence in a mouse skin infection model.

Methods: To assess the contribution of SUB6 to virulence, SUB6-deleted (ΔSUB6) and complemented strains were generated by genetic transformation. The pathogenicity of these strains was compared with that of the parental strain in vivo in mice, based on the evolution of skin symptoms, histopathological lesions and molecular analyses targeting the expression of host pro-inflammatory genes and fungal genes encoding subtilisins from the same family as SUB6.

Results: The ΔSUB6 strain induced superficial skin signs and histopathological inflammatory lesions similar to those caused by the parental strain. Significant overexpression of the SUB1, SUB3, SUB8 and SUB10 genes in the tissues was observed regardless of the strain tested, with no difference between these strains, reflecting the absence of any compensatory mechanism among subtilisins.

Conclusions: SUB6 appears to be more of a marker of fungal infection than a virulence factor, at least acting alone.

Paracoccidioidomycosis (PCM) is a deep systemic mycosis caused by Paracoccidioides brasiliensis. PCM affects predominantly men in their fifth and sixth decades of life, with low prevalence in women. The reasons for this discrepancy are not fully understood, but oestrogen may influence the transformation of the fungus and modulate the immune response.

Objective: To describe and correlate the clinical and histopathological characteristics of oral PCM in women.

Material and methods: This study analysed 45 cases of oral PCM in women, collecting clinical data such as age, smoking and alcohol consumption habits, pain, lesion location, duration of symptoms, presence of unique or multifocal lesions, as well as associated findings such as skin lesions, lymphadenopathy and systemic alterations. Additionally, histopathological characteristics were examined, including the presence of fungi, the quantity of multinucleated giant cells and the presence of well-organised granulomas, non-granulomatous areas, microabscesses and pseudoepitheliomatous hyperplasia. All data were recorded, tabulated and subjected to statistical analysis. Fungal quantification in the analysed slides was performed using the QuPath software, counting each fungal structure and analysing it based on the calculated specimen area.

Results: The average age of patients was 44.18 years (range: 20-68 years). Over half (53.3%) were smokers and 20% were alcoholics. Most lesions were multifocal (51%), with the alveolar ridge being the most commonly affected site, and pain was reported by 68.89% of the patients. Histopathologically, 33.33% of lesions had a low count of visible fungi per square millimetre, 37.78% had a moderate count and 28.89% had a high count. Most lesions (82.22%) contained many multinucleated giant cells, 55.56% had well-organised granulomas, 75.56% presented with microabscesses and 88.89% showed pseudoepitheliomatous hyperplasia.

Conclusion: Despite its rarity in women, PCM has similar clinical and histopathological features compared to those in men and should be considered in the differential diagnosis of unique and multifocal ulcerated lesions.

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: The relationship between asthma and coccidioidomycosis has not been fully described. We have hypothesised that Coccidioides could trigger inflammatory airway responses, similar to other fungi.

Objectives: To estimate the frequency of new-onset asthma-related symptoms after coccidioidomycosis and identify potentially associated factors.

Patients/methods: We used a large health insurance claims database to identify patients with coccidiomycosis with and without an asthma diagnosis code or a short-acting β₂ agonist prescription in the year after diagnosis.

Results: Thirteen per cent of 1657 patients with an asthma diagnosis code or a short-acting β₂ agonist prescription (median 2.5 months later).

Conclusions: Increased healthcare provider awareness of asthma as a potential coccidioidomycosis complication could benefit patients, especially female patients and patients with severe pulmonary infection.

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.