Mycoses最新文献

Background: Cryptococcus bloodstream infections (BSIs) or cryptococcaemia are severe opportunistic infections with high mortality, predominantly affecting immunocompromised individuals or those with end-stage organ disease. Population-based studies examining infection trends and associations between host factors, geography, antifungal resistance, and clinical outcomes are few.

Methods: Blood cultures with growth of Cryptococcus species were retrospectively identified over a 20-year period (January 1, 2000-December 31, 2019) from a state-wide database. Clinical, microbiological and outcome information was also obtained. Survival analyses were used to establish associations between clinical or microbiological characteristics and mortality.

Results: A total of 118 cryptococcaemia episodes (115 patients) were identified, with Cryptococcus neoformans complex causing 98 episodes (83.1%). HIV-associated infections represented 28 episodes (23.7%), with non-HIV episodes (n = 90) more likely to be associated with comorbidities including solid organ transplantation, malignancy, chronic kidney disease, and rheumatological conditions. Overall, 30-day all-cause mortality was 34%, with higher mortality in non-HIV-associated cases (41.7% vs. 12.5%, HR 0.29; 95% CI 0.09-0.94). Of C. neoformans complex isolates with a fluconazole MIC $\ge$ 8 mg/L, 6 (46%) were observed in the most recent 5-year period. Thirty-day (p = 0.85) and 1-year (p = 0.35) mortality increased in a stepwise fashion with increasing fluconazole MIC values in C. neoformans complex infection. Fifty-three episodes (49.1%) documented isolated cryptococcaemia. Patients with additional sites of infection, including CNS involvement, experienced longer hospital stays. Those living in a regional or remote area (HR 1.33; 95% CI 0.68-2.61) or with older age (HR 1.02; 95% CI 1.00-1.04) experienced higher rates of death, although these findings were not statistically significant.

Conclusion: Cryptococcus BSI is a highly lethal condition, particularly among non-HIV infected individuals. We highlight the prognostic importance of blood culture collection in patients with suspected cryptococcal infection. Identifying contemporary risk factors for mortality is critical to understanding what drives poor outcomes. There is a need for continued surveillance of fluconazole susceptibility among Cryptococcus species.

Introduction: Invasive fungal infections (IFI) are a major clinical challenge, particularly in immunocompromised patients, and are associated with high morbidity and mortality. With the increasing prevalence of immunosuppressive conditions and ageing populations, the incidence of IFI is rising globally.

Objective: This survey aims to evaluate the diagnostic and therapeutic capacities for IFI in Belgium, the Netherlands, and Luxembourg (Benelux), a region of high azole-resistance among Aspergillus fumigatus isolates.

Methods: A survey evaluating the diagnostic and therapeutic capacity for IFI was conducted in the Benelux. Data were collected from specialists via an online case report form between March and September 2023. The survey addressed patient characteristics, access to microbiology labs, diagnostic methods (microscopy, culture, molecular diagnostics, etc.), IFI incidence, and the availability of antifungal drugs and therapeutic drug monitoring.

Results: In total, 32 hospitals responded to the questionnaire (12 [38%] from the Netherlands, 19 [59%] from Belgium and one [3%] from Luxembourg). Antifungal susceptibility tests were available in 29 institutions (91%), constituting 84% of the centres in Belgium and 100% for the Netherlands (p = 0.265). Aspergillus PCR testing was available in 12 centres in Belgium (63%) while in 11 centres in the Netherlands (92%, p = 0.108). Mucorales PCR testing was available in 56% of centres. Treatment with at least one amphotericin B formulation was only available in 84% of the responding centres. Therapeutic drug monitoring (TDM), although recommended, was possible for voriconazole in 26 centres (81%) while for posaconazole in 24 centres (75%). Significantly more testing (diagnostic tests and TDM) was outsourced in Belgium compared to the Netherlands (p < 0.001).

Conclusions: Antifungal susceptibility testing is widely available in Belgium and the Netherlands, but implementation in areas with high azole resistance for Aspergillus fumigatus is not yet universal, and techniques vary. Tests for coinfections, like Mucorales PCR, were only available in half of the centres. More testing is outsourced in Belgium, likely due to differences in reference centre organisation, country size, transport, and reimbursement. Delays in diagnosis can impact patient outcomes, so awareness of test availability and transport times is crucial.

Introduction: Invasive candidiasis is a life-threatening fungal infection associated with high mortality rates. Adherence to clinical practice guidelines (CPG) has been shown to improve patient outcomes. This study aimed to evaluate physician compliance with CPG following the implementation of care bundles and locally developed CPG and to assess the impact of CPG implementation on patient mortality.

Methods: This quasi-experimental study utilised a historical cohort control design. Candidemia patients treated at Siriraj Hospital in Bangkok, Thailand, from November 2021 to April 2024 were enrolled. A prospective cohort group received CPG for invasive candidiasis, modified from ESCMID recommendations, covering eight facets. Education care bundles, including clinical policy, training, infographic sheets, leaflets and SMS alerts, were also implemented. Each CPG item was scored as 0, 1 or 2, representing non-compliance, partial compliance and full compliance, respectively. A total compliance score below eight indicates poor compliance. Physician compliance and 30-day mortality rates were analysed.

Results: A total of 112 patients were included in the study: 56 in the historical control group and 56 in the prospective intervention group. Both groups exhibited similar baseline characteristics and risk factors for candidemia. Following the implementation of the CPG and care bundles, physician compliance significantly improved across several metrics. Notable increases were observed in: initiating anti-fungal therapy within 24 h (OR = 6.00, 95% CI [2.41-14.96], p < 0.001), receipt of appropriate anti-fungal therapy, specifically with echinocandins or amphotericin B (OR = 9.17, 95% CI [1.11-75.96], p = 0.03), catheter removal or source control within 48 h (OR = 37.17, 95% CI [4.68-295.39], p < 0.001), obtaining blood cultures at least every other day (OR = 19.15, 95% CI [7.35-49.86],p < 0.001), continuing anti-fungal therapy for at least 14 days after the first negative culture (OR = 3.30, 95% CI [1.42-7.67], p = 0.005), conducting echocardiography (0% vs. 16.1%, p = 0.003), performing fundoscopy (OR = 5.24, 95% CI [1.79-15.30], p = 0.001). There was a significant improvement in compliance scores, with ≥ 8 being more prevalent in the intervention group compared to controls (OR = 5.39, 95% CI [1.98-14.69], p < 0.001). The mean compliance score was 8 ± 2 in the control group and 11 ± 2 in the intervention group (p < 0.001). Additionally, the all-cause 30-day mortality rate decreased significantly from 55.4% in the control group to 35.7% in the intervention group (OR = 0.45, 95% CI [0.21-0.96], p = 0.04).

Conclusions: The implementation of CPG and care bundles for invasive candidiasis significantly enhanced physician compliance and improved patient survival. These findings support the continued adoption of CPG and care bundles in the management of invasive candidiasis.

Background: Small studies have used various serological methods to evaluate the response to paracoccidioidomycosis (PCM) treatment, with limited use of counterimmunoelectrophoresis (CIE). This study assessed CIE titres during and after PCM therapy and their prognostic value for serological negativity.

Methods: In this retrospective study, we reviewed medical records of patients with positive serology in proven or probable PCM from 2006 to 2021 at University of São Paulo. We performed multivariate logistic regression to identify independent variables associated with CIE titre negativity.

Results: This study included 144 participants, totalling 979 serology samples analysed, with a predominance of middle-aged adults (median age 50 years), males (n = 112, 78%) and chronic form (n = 112, 78%). Trimethoprim-sulfamethoxazole (n = 79, 55%) and itraconazole (n = 55, 38%) were the drugs most commonly used. The median treatment time was 24 months (IQR 16-37). Median initial CIE titre was 1:32 (IQR 1:16-1:128). Thirty-seven patients (26%) had a negative CIE titre, and 105 patients (73%) had CIE titres ≤ 1:4 at the last medical appointment. In multivariate analysis, only positive direct microscopy examination (OR 0.32, p = 0.043) was an independent factor related to non-negativity serology. The time to negativity was shorter in female sex and negative microscopy.

Conclusion: The serology using CIE presented a strong association with clinical response, making it a valuable method for monitoring patients with PCM. Most patients achieved CIE titres ≤ 1:4 during antifungal therapy, which was strongly associated with a successful clinical response.

Acute myeloid leukaemia (AML) patients undergoing venetoclax (VEN)-based regimens are at risk for invasive fungal infections (IFIs), but the benefit of antifungal prophylaxis (AFP) in this setting remains uncertain. We evaluated the efficacy of AFP in preventing invasive fungal infections (IFI), improving overall survival (OS) and best response among AML patients treated with VEN-based therapies. A systematic search of PubMed, EMBASE and Cochrane databases was conducted for studies comparing AFP use to no prophylaxis in AML patients under VEN-based regimens. Data were synthesised using Bayesian meta-analysis. Seven retrospective studies involving 960 patients were included. The pooled analysis yielded an odds ratio (OR) of 0.84 (95% credible interval: 0.39-1.59) for probable or confirmed IFIs with AFP use. The computed probability of OR < 1 for IFI infection was 74.8% for probable or confirmed IFIs and 71.8% for confirmed IFIs, indicating substantial uncertainty and no clear evidence of a real effect. AFP did not significantly alter OS (hazard ratio = 0.82, 95% confidence interval: 0.58-1.16) or response rates. Mould-active antifungals were underutilised in most studies, and the most used antifungals were fluconazole (35.2%) and posaconazole (34.8%). Our analysis highlights the need for prospective studies and risk stratification to evaluate the role of mould-active agents in this population.

Background: Candida (Candidozyma) auris has distinct genetic clades. Clade distinction is relevant for infection control and epidemiological purposes. State-of-the-art typing methodologies for clade distinction are based on genomic approaches, such as short tandem repeat (STR) analysis and whole-genome sequencing (WGS). However, they are time-consuming and expensive. Fourier transform infrared spectroscopy (FT-IR) is an alternative tool for strain typing based on their unique biochemical spectral profiles.

Objectives: To apply FT-IR to differentiate C. auris clades and evaluate epidemiological relationships based on biochemical data among isolates from a multicenter C. auris outbreak in the state of Pernambuco, northeastern Brazil.

Methods: Sixty-nine C. auris strains from clades I, II, III, and IV were analysed. Fifty-nine were clade IV strains obtained from three outbreaks that took place in Pernambuco state, northeastern Brazil. An adjusted FT-IR spectroscopy protocol was applied to obtain carbohydrates and lipid fingerprints. Short Tandem Repeat (STR) analysis was used in order to validate the spectroscopy approach.

Results: The adjusted preparation protocol for FT-IR analysis improved the spectral quality by 31.42% compared to standard protocol. FT-IR allowed us to discriminate C. auris clades I to IV. Moreover, important similarities were observed in C. auris clade IV strains obtained from two of the three hospitals, based on polysaccharides (1300-800 cm^-1) plus lipids (3000-2800 cm^-1 and 1500-1400 cm^-1) spectra. STR confirmed the similarity results obtained by FT-IR, clustering the strains from two different hospitals.

Conclusions: The IR Biotyper is fast, easy-to-use, and a promising alternative for moderate-to-high-complexity laboratories to differentiate C. auris clades. Furthermore, this technique has the potential for isolate-level source tracking, which could be valuable for monitoring transmission routes in clinical settings.

Background and objective: Acute-on-chronic liver failure (ACLF) is associated with significantly higher short-term mortality, and the presence of invasive fungal infection (IFI) further increases this risk. This study aims to develop a ML model that predicts the risk of IFI in ACLF patients.

Methods: This study included 1112 patients divided into a training set and a validation set, with another 188 patients serving as an external validation cohort. The Recursive Feature Elimination (RFE) method was used to select the most significant variables for model development. Four machine learning algorithms were compared to identify the optimal model. The models were evaluated and compared using C-index, time-dependent ROC curves, decision curve analysis (DCA), and calibration curves. The LIME (Local Interpretable Model-Agnostic Explanations) method was used to identify the high-risk populations utilised by the model.

Results: 778 patients were included in the training set, 334 in the internal validation set, and 188 in the external validation set. The study found that Random Forest (RF) was the best-performing ML algorithm. In the training set, the RF model achieved an AUROC of 0.922 (0.911-0.933), significantly higher than MELD (0.854, 0.835-0.873, p < 0.001), CLIF-C OF (0.753, 0.724-0.783, p < 0.001), and CLIF-C ACLF (0.879, 0.863-0.896, p = 0.020). The same trend was observed in both the internal and external validation sets. The time-dependent ROC curve showed that the RF model outperformed the other scores for predicting the risk of IFI in 28 days. DCA and calibration curves also demonstrated superior clinical benefits for the RF model across all datasets. LIME revealed bacterial infection (BI), Na < 136 mmol/L, CRP (C-reactive protein) > 20.1 g/L, and TBIL(Total Bilirubin) > 196.7 μmol/L as the high-risk groups.

Conclusion: The RF model effectively predicts the risk of IFI in ACLF patients. The application of LIME enables the identification of high-risk populations, providing clinical value for patient management.

Background: Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency, predisposing to life-threatening invasive mould infection (IMI). While antifungal prophylaxis has improved outcomes, IMI remains the leading cause of mortality in CGD. This study aimed to evaluate the clinical and fungal epidemiology of IMI among CGD patients in Türkiye and explore diagnostic and treatment challenges.

Methods: Demographics, clinical characteristics, IMI episodes, diagnostic methods, and antifungal prophylaxis regimens of 72 CGD patients followed at the Division of Paediatric Immunology of Marmara, Cerrahpaşa and Çukurova University School of Medicine, Türkiye between 1991 and 2022 were analysed. IMI episodes were classified as proven, probable, or possible based on the European Organisation for Research and Treatment of Cancer/Mycoses Study Group criteria.

Results: Of the patients, 79.1% were male, and 52.8% had autosomal-recessive CGD (AR-CGD). Forty-two IMI episodes were detected in 39 (54.2%) patients, predominantly involving the lungs. Proven IMI accounted for 28.5% of episodes, with Aspergillus fumigatus as the most frequent pathogen. Patients with X-linked CGD experienced earlier IMI onset than AR-CGD (34.0 months (IQR: 18.0-65.5) versus 122.0 months (IQR: 40.25-240.0; p = 0.005)). Presentation with IMI led to the CGD diagnosis in 20 (51.3%) patients, while 19 (48.7%) developed IMI under itraconazole prophylaxis (median: 96.0 months, IQR: 48.0-153.0). Of 13 deaths (18.0%), 84.6% were associated with IMI.

Conclusions: Our study highlights the persistently high burden of IMI among CGD patients, despite antifungal prophylaxis. Challenges in diagnosis, including limited access to invasive biopsy and diagnostic modalities, and gaps in prophylactic monitoring, underscore the need for optimised management strategies.

Purpose: Biologic agents have become a key treatment option for moderate-to-severe plaque psoriasis; however, the associated risk of superficial fungal infections, such as Candida and dermatophytes infections, remains unclear. This study aims to systematically assess the impact of different biologic agents on these infection risks and to compare the differences between them.

Methods: Research questions and keywords were developed based on the Population, Intervention, Control and Outcome (PICO) framework. A systematic search of PubMed, EMBASE, the Cochrane Library and Web of Science was conducted for randomised controlled trials (RCTs) published up to December 2024, using the keywords 'psoriasis', 'biologics', 'anti-IL-17', 'anti-IL-12/23', 'anti-TNF', 'superficial fungal infections', 'dermatophyte infections', 'Candida' and 'onychomycosis'. Meta-analyses were performed using RevMan 5.4 and STATA 16.0 software.

Results: A total of 644 records were identified, with 29 articles included in the final analysis. Meta-analysis indicated that compared with placebo, interleukin-17 (IL-17) inhibitors notably raised the risk of Candida infections (OR = 2.39, 95% CI = 1.84-3.11, p < 0.00001), whereas tumour necrosis factor-alpha (TNF-α) inhibitors (OR = 1.75, 95% CI = 0.53-5.82, p = 0.36) and interleukin-12/23 (IL-12/23) inhibitors (OR = 1.11, 95% CI = 0.27-4.63, p = 0.88) showed no significant differences. Cross-comparison demonstrated that IL-17 inhibitors had a higher risk of Candida infection compared to TNF-α inhibitors (OR = 2.23, 95% CI = 1.08-4.57, p = 0.03) and IL-12/23 inhibitors (OR = 4.21, 95% CI = 2.71-6.55, p < 0.00001). For dermatophyte infections, the overall risk associated with biologic agents was increased (OR = 1.89, 95% CI = 1.19-3.01, p = 0.007), IL-17 inhibitors showed a higher risk compared to IL-12/23 inhibitors (OR = 2.70 95% CI = 1.29-5.63, p = 0.008). Overall, biologic agents significantly increased the risk of superficial fungal infections compared to placebo (OR = 2.10, 95% CI = 1.73-2.55, p < 0.00001).

Conclusion: Biologic agents, particularly IL-17 inhibitors, notably increase the risk of superficial fungal infections in psoriasis patients. In clinical practice, targeted monitoring protocols should be established, including regular follow-up to promptly detect superficial fungal infections and initiate antifungal treatment as necessary.

Trial registration: PROSPERO: CRD42025636705.

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has been reported worldwide. However, studies in Japan are limited, and no study has evaluated the relationship between the incidence of CAPA and specialist involvement in its diagnosis.

Objectives: We aimed to obtain new epidemiological data on CAPA in Japan and evaluate the relationship between the incidence of CAPA and specialist involvement in its diagnosis.

Methods: A survey was conducted among chief physicians at 760 training hospitals with at least 100 beds and accredited by the Japanese Respiratory Society or the Japanese Association for Infectious Diseases. Critical patients with COVID-19 diagnosed with CAPA between 1 January 2020 and 31 August 2023 were analysed. A literature review was conducted to evaluate the correlations between the incidence of CAPA and galactomannan (GM) testing and positivity rates.

Results: Responses were obtained from 221 of the 760 hospitals (29.1%). The incidence of CAPA was 0.67% (69/10,276). Hospitals with patients with CAPA had significantly more pulmonologists and infectious disease specialists than those without patients with CAPA. A strong positive correlation was observed between the incidence of CAPA and the number of pulmonologists per critical patient with COVID-19 (r = 0.824, p < 0.001). The literature review showed that bronchoalveolar lavage fluid GM testing rate was a strong positive correlation with the incidence of CAPA (r = 0.527, p = 0.014).

Conclusions: For the diagnosis of CAPA, its recognition by specialists primarily involved in managing critical patients with COVID-19 seems essential.