Candida bloodstream infection (C-BSI) is a rare infection in patients with left ventricular assist devices (LVADs). We aim to describe the characteristics and outcomes of C-BSI. We performed a retrospective search for C-BSI in patients with LVADs at our institution from January 2012 to May 2024. We then performed a literature review using the keywords 'fungemia ventricular assist device', 'candidemia ventricular assist device', 'Candida bloodstream infection ventricular assist device,' or 'Candida endocarditis ventricular assist device' from 1990 to 2024. Clinical characteristics and outcomes were extracted. We identified three institutional cases along with 21 additional cases from the literature. The incidence of candidemia was 3.1% (3/97) and 1.8% (16/867), respectively, in the case series and literature review. Mean age was 45.6 years (range 19-73 years), and average body mass index (BMI) was 31.8 kg/m². There was a 100% mortality rate in our cohort and 62.5% in the literature review cohort. Among the surviving patients in the literature review, 66.7% underwent heart transplantation, and 33.3% were discharged on antifungal therapy. 41.2% experienced right heart failure, with four requiring temporary mechanical circulatory support post-operatively. Obesity was present in 75.0% of patients, and 42.1% had an LVAD-related infection. C-BSI developed after an average of 426 days of LVAD support, with 33.3% occurring within 30 days postoperatively. The average duration of C-BSI was 29 days. Candida auris was the most common species. C-BSI is a rare fatal complication in LVAD patients. Obesity, delayed sternal wound closure, and right heart failure may contribute to these poor outcomes.
Entomophthoromycosis is a chronic fungal granulomatous disease caused by Basidiobolus and Conidiobolus species. This disease is associated with significant morbidity and prolonged treatment. This systematic review aims to address the epidemiology, clinical features, diagnostic methods, therapeutic strategies, and clinical outcomes of entomophthoromycosis. Medline, Embase, Scopus and Web of Science databases were searched using appropriate keywords for entomophthoromycosis from 1 January 2000 to 31 December 2023. A total of 405 cases of entomophthoromycosis were included; of those, Basidiobolomycosis (n=241/405, 59.5%) was the most common, followed by conidiobolomycosis (n=123/405, 30.4%) and unclassified entomophthoromycosis (n=41/405, 10.1%). Distinct epidemiological patterns were observed: basidiobolomycosis was most commonly reported from Middle Eastern countries (n=139/241, 57.7%), whereas conidiobolomycosis was most commonly reported from Southeast Asian countries (n=97/123, 78.9%). The common clinical forms seen in basidiobolomycosis were gastrointestinal (n=164/241, 68%) and cutaneous (n=64/241, 26.6%) disease, and rhino-facial disease (n=114/123, 92.7%) in conidiobolomycosis. Demonstration of fungal hyphae by histopathology or by direct microscopy is the most common diagnostic method (n=377/405, 93.1%). Culture positivity was higher in conidiobolomycosis (n=94/123, 76.4%) than in basidiobolomycosis (n=108/241, 44.8%). Antifungal treatment with surgery (n=129/231, 55.8%) was the common treatment strategy for basidiobolomycosis. Antifungal therapy alone (n=77/112, 68.8%) was the most commonly used treatment for conidiobolomycosis. Itraconazole was the most common antifungal used in treatment (n=228/357, 63.9%), followed by potassium iodide (n=104/357, 29.1%). Overall mortality of the cohort is 10.93% (n=40/366). Gastrointestinal basidiobolomycosis has a higher mortality (n=28/150, 18.7%). Both these diseases exhibit different geographic patterns and clinical forms. The disease mimics malignancies and other inflammatory diseases; high clinical suspicion is essential for prompt diagnosis and initiation of therapy to improve clinical outcomes.
Although candidemia is among the most common invasive fungal infections in hospitalized patients, the persistence of bloodstream infection despite antifungal therapy remains poorly characterized. We performed a retrospective, matched case-control study of persistent candidemia (PC) across three tertiary care centers in the United States over a seven-year period (2018-2025). PC was defined as at least 72 hours of positive blood cultures with the same Candida species from the start of active antifungal therapy. Cases were matched 1:2 to controls with non-persistent candidemia by diagnosis date. Associations were evaluated using conditional logistic regression within matched strata. The cohort included 47 PC cases and 94 matched controls. Compared with controls, cases were more likely to have a central venous catheter (CVC) at candidemia onset and be in the intensive care unit at diagnosis. Intra-abdominal sources were more common with PC. In multivariable analyses, CVC presence (adjusted odds ratio (aOR) 4.58, 95% CI 1.39-15.09) and ICU status (aOR 3.10, 95% CI 1.10-8.72) were associated with persistence, while male sex was inversely associated (aOR 0.21, 95% CI 0.08-0.60; P = 0.004). PC was associated with longer duration of hospitalization (median 36 vs 19 days; P < 0.001) and higher 30-day all-cause mortality (40.4% vs 22.3%; P = 0.040). In summary, PC was associated with higher mortality and longer hospital stays than non-persistent candidemia. Central venous catheter presence and intensive care unit status were independently associated with persistence.
Alternaria spp. are dematiaceous ascomycetes that can cause opportunistic infections in immunocompromised hosts. They are challenging to identify and treat. However, optimal antifungal therapy remains undefined. We retrospectively reviewed antifungal susceptibilities (AST) of all Alternaria spp. isolates from adults at a tertiary care center between 2011 and 2025. We evaluated culture sources, minimum inhibitory concentration (MIC) and minimal effective concentration (MEC) distributions, and MIC₅₀/MIC₉₀ and MEC50/MEC90 values. Clinical characteristics, treatment measures, and outcomes of patients with clinically significant Alternaria spp. infections were described. Forty-one patients had Alternaria spp. isolated, most commonly from skin (n = 13), bone/joint (n = 5), nail (n = 3), or cornea (n = 3). Posaconazole and itraconazole demonstrated low MICs (MIC₅₀/MIC₉₀: 0.06/0.5 and 0.25/0.5 µg/mL, respectively). Voriconazole and isavuconazole showed higher MIC₅₀/MIC₉₀ (1/2 and 2/4 µg/mL). Caspofungin (0.125/0.5 µg/mL) and amphotericin B (0.25/1 µg/mL) had low MICs and MECs.s. Alternaria spp. represented clinically significant infection in 27 cases (66%); 26% were solid organ transplant recipients and 15% had hematologic malignancies. Other risk factors included preceding trauma (22%) and autoimmune disease (15%). Posaconazole was the most frequently used empiric agent (6, 32%). Following AST results, 14 patients (52%) received oral antifungal therapy; posaconazole was used in all 14. In addition, 7 patients (26%) received combination therapy with IV amphotericin B. Adjunctive surgery occurred in 14 cases (52%). Five patients (19%) died before completing therapy; Alternaria infections occurred predominantly in immunocompromised hosts and were frequently managed with posaconazole and surgery. Interpretive criteria for Alternaria spp. are needed to guide empiric and definitive therapy.
OBJECTIVES:Candida parapsilosis is a leading cause of invasive candidiasis globally, with rising reports of fluconazole resistance threatening its clinical management. Among the mechanisms involved, gain-of-function mutations in the MRR1 gene have emerged as key drivers of antifungal resistance. We aimed to investigate a novel amino acid substitution (G982E) in the Mrr1 zinc cluster transcription factor, identified in a fluconazole-resistant C. parapsilosis isolate from a patient exposed to fluconazole. METHODS:Using CRISPR-Cas9 genome editing, we introduced the G982E variant into two fluconazole-susceptible C. parapsilosis genetic backgrounds. The antifungal susceptibility of the engineered mutants was assessed in vitro against a broad panel of systemic antifungal agents. A Galleria mellonella infection model was also used to evaluate the impact of the G982E variant on antifungal treatment efficacy and virulence in vivo. RESULTS:Acquisition of the G982E substitution dramatically altered the antifungal susceptibility profile, particularly for fluconazole for which the MIC increased to >256 µg/mL. However, the magnitude of the MIC increase varied by azole, with the greatest increase seen for fluconazole (>9-10-fold), followed by voriconazole (5-fold), isavuconazole (3-fold), but also flucytosine (1.5-fold). In contrast, susceptibility to posaconazole remained largely unchanged. In vivo, this new variant conferred fluconazole treatment failure but was associated with a significant reduction in virulence. CONCLUSIONS:The G982E is a novel Mrr1 gain-of-function mutation driving high-level fluconazole resistance in C. parapsilosis. These findings reinforce the central role of Mrr1 in antifungal resistance, underscore the functional diversity of its mutational landscape, with potential implications for fungal fitness and transcriptional regulation.
Trichophyton mentagrophytes ITS-genotype VII (TMVII) is a globally emerging sexually transmitted dermatophyte causing severe skin infections characterised by painful, pustular lesions on the face, public area, genitalia, and trunk. To inform the prevention efforts, we present the first draft genomes of four TMVII isolates obtained from patients in the United Kingdom diagnosed between 2021 and 2025. We performed whole-genome sequencing and phylogenetic analysis based on single-nucleotide polymorphisms. We analysed the genetic relatedness of four TMVII isolates collected from UK patients, two had travel links to Spain and the Middle East. Two further isolates, including T. mentagrophytes ITS-genotype I/II obtained from a canine infection in the United Kingdom in 2025 and Trichophyton indotineae were sequenced for contextual analysis. We confirm that the TMVII strains studied here represent a highly clonal population, distinct from both zoophilic T. mentagrophytes genotype I/II and anthropophilic T. indotineae.
COVID-19-associated pulmonary aspergillosis (CAPA) is a recognized fungal superinfection, but diagnosis remains difficult due to non-specific clinical and radiological findings. While anti-Aspergillus spp. IgG antibodies (AspAb) are used for chronic aspergillosis diagnosis, their role in this context is unclear. We described AspAb kinetics in CAPA patients hospitalized in intensive care unit (ICU). We performed a retrospective study at Lille University Hospital from February 2020 to December 2021, enrolling ICU SARS-CoV-2 patients. Patients were included if they had at least one positive mycological marker - direct examination, culture, galactomannan antigen (GM) or Aspergillus fumigatus qPCR in bronchoalveolar lavage and/or serum - along with clinical and radiological findings consistent with CAPA, as defined by the 2020 ECMM/ISHAM consensus criteria. Among 898 patients, 95 (10.6%) had at least one positive mycological marker; 47 fulfilled CAPA criteria (5.2%), and 43 had at least one AspAb measurement. One-quarter of CAPA patients (23.3%, 10 patients) had at least one positive AspAb measurement (one of whom had only one measurement). Among AspAb-positive patients, 7 (70.0%) seroconverted a mean of 8.3 days (SD, 8.5) after CAPA diagnosis; one had documented positivity prior to hospitalization. Seven patients (70.0%) reached AspAb rate ≥ 80 AU/mL. These results are the first observed in CAPA patients and need to be confirmed in a larger cohort of non-neutropenic patients hospitalized in ICU with viral pneumonia.
Microsporum canis complex infections remain a major cause of pediatric dermatophytosis, yet molecular epidemiologic and antifungal susceptibility data from the Arabian Gulf are scarce, with no contemporary regional assessment since 1981-1988. We characterized the clinical, molecular, and antifungal susceptibility profiles of M. canis complex isolates in Abu Dhabi and assessed concordance between phenotypic and ITS-based identification. Fifty-two clinical dermatophyte isolates collected through passive surveillance at the UAEU Fungal Reference Laboratory (September 2024-December 2025) underwent phenotypic identification, ITS sequencing, and antifungal susceptibility testing (CLSI M38). Clinical data were available for 48 patients. ITS sequencing identified 47 isolates (90.4%) as M. canis and 5 (9.6%) as the M. audouinii clade, with phenotypic discordance in 9.6% of isolates (including one M. canis misidentified as Trichophyton rubrum). The cohort was predominantly pediatric (79.2% ≤12 years; 54.2% female). Tinea capitis predominated (60.4%), followed by tinea corporis (20.8%) and multifocal disease (16.7%). Cat exposure was reported in 50% and infected household contact in 27.1%. All isolates showed low MICs (terbinafine MIC₅₀/₉₀ 0.015/0.03; itraconazole ≤0.03/0.06; voriconazole ≤0.03/≤0.03; griseofulvin 0.125/0.25; fluconazole 4/8 µg/mL). Despite this, 81.2% (26/32) of patients with follow-up experienced treatment failure or recurrence, with no clear MIC-outcome association. This first molecular and antifungal characterization of M. canis complex infections in the UAE over three decades showed that ITS sequencing corrected phenotypic identification in nearly 10% of cases. High recurrence despite low MICs suggests limited predictive value of in vitro susceptibility, supporting species directed management, molecular confirmation, species-directed management, and One Health strategies.
Triazole antifungal drugs (TADs) are widely used in clinical practice but carry a risk of severe cutaneous adverse reactions (SCARs). However, comprehensive real-world evidence regarding the comparative safety profiles of individual TADs remains limited. This research aimed to investigate and compare the real-world risk, clinical characteristics, and time-to-onset of SCARs associated with individual TADs. The SCAR cases with TADs as the primary suspect drug were identified in the FDA Adverse Event Reporting System. Disproportionality analysis and Bayesian methods were employed to detect safety signals with Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). Differences of clinical features, outcomes, time-to-onset (TTO), and signal strength at the preferred term (PT) level were analyzed. A total of 1429 SCAR cases with five TADs were identified. Fluconazole showed the strongest and most consistent statistical association across all four algorithms (ROR = 5.2), followed by itraconazole. Voriconazole yielded mixed signals (positive by ROR and BCPNN only), while Posaconazole and Isavuconazole exhibited no significant SCAR signals. Voriconazole was associated with the highest mortality proportion (12.8%), followed by posaconazole (10%). The median TTO for SCARs was 8 days, with voriconazole having the longest delay (16 days). At the PT level, 45 distinct signals were identified, including high-risk manifestations such as fixed eruption (ROR = 24.43), mucosal ulceration, and SJS/TEN overlap. This study identified significant variability of SCARs signals among triazole antifungals. These findings support early risk recognition and informed antifungal selection in clinical practice.
Zoological collections represent unique environments in which captivity-related alterations of host microbiota may increase susceptibility to infectious diseases. While reptiles are recognized reservoirs of microorganisms, data on quantitative yeast colonization and antifungal susceptibility in captive lizards remain limited. This study assessed 28 lizards belonging to nine species housed in a zoological park in southern Italy. Skin and cloacal swabs (n = 56) revealed yeast growth in 75% of animals and 57.1% of samples, with positivity rates of 60.7% and 53.6% for skin and cloacal samples, respectively. MALDI-TOF MS and ITS region sequencing identified 113 isolates belonging to 17 distinct fungal species, including Arthrographis spp., Meyerozyma spp., Candida spp., Pichia spp., Trichosporon spp., and others. Arthrographis kalrae was the predominant species (i.e., 36.3%), followed by Meyerozyma guilliermondii (i.e., 16.8%). Mean colonization loads were 4.25 CFU/swab for skin and 10.50 CFU/swab for cloacal samples. Eight species were considered clinically relevant, including the Candida parapsilosis complex, Pichia kudriavzevii, and Trichosporon asahii. Antifungal susceptibility testing performed according to Clinical and Laboratory Standards Institute (CLSI, 2022) guidelines revealed marked phenotypic heterogeneity and frequent elevation of minimum inhibitory concentration (MIC). Above-threshold MICs differed significantly according to yeast species, antifungal compound, and sampling site. Non-wild-type phenotypes and elevated MICs were observed across multiple antifungal classes, with amphotericin B >64 µg/ml and fluconazole >256 µg/ml in several isolates (i.e., 92.3% and 75.0%, respectively). Reduced susceptibility or resistance was evident in Clavispora lusitaniae, M. guilliermondii, and Wickerhamomyces anomalus. These findings support the hypothesis that captive lizards may represent asymptomatic reservoirs of opportunistic and potentially antifungal-resistant yeasts, emphasizing the importance of hygiene measures and microbiological surveillance in zoological settings.
We assessed the Pneumocystis jirovecii PCR accuracy on non-invasive oropharyngeal wash (OW) specimens for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-HIV immunocompromised patients. In this retrospective study, 134 patients with suspected PJP undergoing both OW and deep respiratory sampling were included. PJP was defined by composite criteria. OW P. jirovecii PCR showed a sensitivity of 61.5% (95% CI 42.5-77.6) and a specificity of 97.2% (95% CI 92.2-99.1). Positive and negative predictive values were 84.2% and 91.3%, respectively. These results suggest OW P. jirovecii PCR may support non-invasive diagnosis, but cannot be used to exclude PJP.
Coccidioidomycosis is an endemic fungal disease in arid regions of the Americas, yet population-level exposure in Mexico remains poorly defined. This study aimed to evaluate the frequency and spatial distribution of asymptomatic individuals with anti-Coccidioides IgG antibodies residing in different municipalities of Sonora, Mexico, and to evaluate the environmental factors associated with the seropositivity presented. A cross-sectional serosurvey was conducted using 534 serum samples collected from 15 laboratories at different municipalities of Sonora. Anti-Coccidioides IgG antibodies were detected using a commercial enzyme immunoassay. Seroprevalence was analyzed by demographic characteristics, and to evaluate whether environmental conditions differed between municipalities with and without evidence of Coccidioides spp. exposure, mean values of 19 bioclimatic variables were calculated. Overall, IgG seropositivity was 7.3%, with an additional 15% showing indeterminate results. Higher seropositivity was observed among young adults and in individuals that reported no travel to endemic regions in the United States of America. The Mann-Whitney U test identified a significant difference only for temperature seasonality (BIO4) between municipalities with and without seropositive individuals; this difference remained significant after correction for multiple comparisons. These findings provide serological evidence of exposure to Coccidioides spp. in nine municipalities of Sonora. The indeterminate percentage of 15% in an area considered endemic is striking and given that the chosen test is designed for diagnosis, lower cut-off points should be considered for serological surveillance or prevalence studies in asymptomatic populations to provide more information on the hidden burden of coccidioidomycosis in endemic regions.
Scedosporium is an emerging opportunistic filamentous fungus widely distributed in soil and stagnant water. Mortality remains substantial and management is often challenging due to intrinsic antifungal resistance and delays in diagnosis. In this retrospective cohort study, we describe the clinical spectrum, microbiological characteristics, and outcomes of microbiologically culture-confirmed scedosporiosis at a tertiary care centre in South India between May 2016 and August 2024. A total of 18 patients were included, with a median age of 54 years and a predominance of male patients. Contrary to the patterns described in many Western and transplant-focused cohorts, the majority of infections in our series involved osteomyelitis and paranasal sinus disease. Disseminated infection was rare but was associated with poor outcomes. Voriconazole-based therapy was the most commonly used antifungal regimen, and surgical intervention was required in six cases. Our findings highlight a distinct clinical pattern of scedosporiosis in our setting, with osteomyelitis and sinusitis emerging as predominant presentations. These observations emphasize the importance of maintaining a high index of suspicion for Scedosporium infection in chronic bone and sinus disease, particularly when patients fail to respond to conventional antibacterial therapy.
Pichia kudriavzevii (previously known as Candida krusei) is among the top five causative agents of candidemia, mainly affecting neonates. The yeast is intrinsically resistant to fluconazole, and nosocomial transmission has been reported. Recently, whole genome sequencing (WGS) analysis on 24 out of 165 clinical P. kudriavzevii isolates from Delhi, India showed two clusters, indicating nosocomial transmission. To further increase our insight into the transmission of this fungus in healthcare settings, we performed short tandem repeat (STR) genotyping of 106 isolates from Delhi, India, and compared outcomes to STR genotypes and WGS data of isolates originating from various countries. A total of 52 unique genotypes were identified, in addition to five clusters comprising two to 22 isolates. Four of these clusters were restricted to a single hospital, while the largest cluster included six hospitals. Interestingly, when compared to a global collection, Iranian clinical isolates were identical to the multicenter cluster and also related to isolates from the Netherlands and Sri Lanka, the latter isolate being collected in 1935. WGS analysis on a selection of isolates confirmed the clusters identified by STR analysis, underscoring the high discriminatory power of the STR genotyping scheme. In short, we report several events of single-center nosocomial transmission of P. kudriavzevii in India. One multicenter cluster was found, which was closely related to isolates originating from diverse countries, suggesting a fitness advantage or elevated transmission potential for this lineage.
Coccidioidomycosis (Valley Fever) is a fungal infection endemic to the southwestern United States. Meningitis occurs in approximately 1% of cases and often results in hydrocephalus necessitating shunting and lifelong antifungal therapy. Prior studies lack comparison with contemporaneous controls. In this study, we compare radiographic, laboratory, and longitudinal shunt survival data until revision and reprogramming. The objective was to compare the 7-year outcomes between patients who underwent shunting with and without coccidioidomycosis meningitis (CM). We identified neurosurgical patients who underwent initial shunt placement for hydrocephalus over 7 years at the University of Arizona-Tucson. Demographics, shunt characteristics, failure rates, imaging findings, operative complications, revision etiology, reprogramming rates, and mortality were compared. Of 180 initial shunt placements, 19 (11.7%) had CM. No differences in revision rates, reprogramming rate, time to first revision, or mortality were observed with antisiphon use. CM patients had lower mean final shunt pressures (56.9 ± 24.1 mmH₂O in CM (95% CI, 45.3-68.5 mmH₂O) vs. 76.3 ± 40.2 mmH₂O in non-CM (95% CI, 70.3-83.3 mmH₂O), P = 0.04) at a mean follow-up of approximately 1.7-1.9 years. Two-year shunt survival was 65.5% in CM (95% CI, 38.4%-82.9%) vs. 70.4% in Non-Coccidioidomycosis (non-CM) (95% CI, 60.9%-78.0%) (P = 0.71); patient survival was 92.3% in CM (95% CI, 56.6%-98.9%) vs. 89.5% in non-CM (95% CI, 82.1%-93.8%) (P = 0.97). Anti-siphon valves were used in 78.9% of CM patients (95% CI, 54.4%-93.9%) vs 74.5% of non-CM patients (95% CI, 67.1%-81.1%) (P = 0.67). Despite similar valve types and revision etiologies, the data suggests CM-related hydrocephalus treatment requires lower shunt pressures over time and may indicate differences in intracranial compliance dynamics in CM patients.
Kerion celsi remains a significant public health concern in eastern Turkey. This study aimed to evaluate the clinical, demographic, and mycological characteristics of patients diagnosed with kerion celsi, a condition that continues to be relatively common in this region. A total of 65 pediatric patients who were hospitalized in our dermatology clinic between December 2015 and December 2016 were included in the study. During epilation, which is routinely performed as part of the treatment, hair and skin samples were collected to identify the causative agents. All samples underwent standard microbiological procedures for fungal identification. Of the patients, 51 (78.5%) were male and 14 (21.5%) were female. The ages ranged from 1 to 13 years, with a mean age of 6.45 years. Regarding seasonal distribution, 6 patients (9.2%) were admitted in summer, 10 (15.4%) in autumn, 27 (41.5%) in winter, and 22 (33.8%) in spring. The majority of patients (56; 86.2%) were from rural areas, while only 9 (13.8%) resided in urban settings. Fungal growth was detected in 23 samples (35.3%), whereas no growth was observed in 42 samples (64.7%). Among the culture-positive cases, Trichophyton (T.) verrucosum was the most frequently identified species, accounting for 9 cases (38.7%). In conclusion, our findings indicate that T. verrucosum was the predominant etiological agent of kerion celsi in eastern Turkey. Additionally, the study reported the presence of fungal species not previously described in Turkey.
Serum A. fumigatus-IgG is the cornerstone serological test for diagnosing chronic pulmonary aspergillosis (CPA), but its sensitivity is imperfect. A multiplex Aspergillus antigen preparation (mx4) incorporating extracts of A. fumigatus, A. flavus, A. niger, and A. terreus is commercially available. We aimed to compare the diagnostic performance of the serum mx4-IgG assay with the A. fumigatus-IgG assay for diagnosing CPA. We prospectively enrolled 332 consecutive adults with suspected CPA at a tertiary chest clinic between August 2022 and July 2025. Serum IgG against mx4, A. fumigatus, A. flavus, A. niger, and A. terreus was measured using a fluorescent enzyme immunoassay. Diagnostic performance was evaluated against a primary composite reference standard and two alternative serology-based definitions. Hierarchical diagnostic algorithms and a simplified cost analysis were performed. Of 332 participants, 230 had CPA, and 102 were diseased controls (patients with structural lung disease). Against the primary reference standard, the mx4-IgG assay achieved a sensitivity of 83.0% and specificity of 73.5%, compared with 95.2% and 88.2%, respectively, for the A. fumigatus-IgG assay. Similar findings were observed using alternative serology-based CPA definitions. In hierarchical testing, a sequential strategy of A. fumigatus-IgG and A. flavus-IgG identified 97.7% of CPA cases at the lowest cost (USD 24/patient) and outperformed strategies incorporating the mx4-IgG assay (mx4-IgG followed by A. fumigatus-IgG). The mx4-IgG assay was not superior to the A. fumigatus-IgG assay for diagnosing CPA. Sequential testing with A. fumigatus-IgG followed by A. flavus-IgG achieved the highest diagnostic yield at the lowest cost and warrants further evaluation.
Our Transplant Infectious Disease (TID) program implemented monitoring of all elevated bronchoalveolar lavage (BAL) galactomannan (GM) results as a quality improvement (QI) project. Twenty-four hours after a positive result, a standardized email is sent to the primary providers if the GM result is unaccounted for based on clinical documentation. We performed a real-world, retrospective study to examine the impact of this intervention over one year (2022-2023) as well as the impact of an elevated BAL GM result on clinical decision-making. We captured the number of positive GM results that triggered notification of the primary team, and the number of times a single positive galactomannan triggered initiation or change of systemic antifungal therapy. We included 55 cases of BAL GM >1.0. In seventeen cases (31%), a single positive BAL GM result triggered the initiation of antifungal therapy. Most of these cases met criteria for probable IPA. The TID team contacted the primary team for 14 cases (25%) of elevated BAL galactomannan antigens, which led to a new start or change in antifungal regimen. Voriconazole was the most common definitive antifungal agent chosen. Though elevated BAL GM results were impactful in introducing or changing antifungal regimens, we identified a possible knowledge gap in the interpretation of elevated galactomannan results among clinical staff. Our study suggests that there may be value in the diagnostic stewardship and monitoring of BAL galactomannan results by infectious disease clinicians.
The cryptococcal antigen lateral flow assay (CrAg LFA) is a widely available point-of-care test for the diagnosis of cryptococcal meningitis. Although there have been some reports of cross-reactivity with Trichosporon species, the extent of cross-reactivity among basidiomycetous yeasts has not been widely explored. We tested a range of basidiomycete yeast isolates using a CrAg LFA to examine potential cross-reactivity, with positive results for all isolates belonging to Trichosporon and Naganishia species, and for some isolates of Cutaneotrichosporon, Filobasidium and Ustilago species. While these species rarely cause invasive infection, the potential for cryptococcal antigen cross-reactivity should be considered.
Cryptococcus gattii complex has emerged as an important cause of invasive fungal disease in both immunocompetent and immunocompromised hosts, yet robust clinical and epidemiological data remain limited, particularly in Latin America. An observational study was conducted to describe and analyze the clinical characteristics and outcomes of all proven and probable cases of C. gattii complex infection managed at a tertiary referral center in southern Brazil from 1992 to 2025. A total of 39 cases were identified. The median age was 54 years, and 61.5% were male. Most patients (61.5%) were considered immunocompetent, although comorbidities were common. Headache (61.5%), altered mental status (33.3%), and fever (30.8%) were the most frequent symptoms overall. Pulmonary disease was the predominant clinical form (76.9%), but meningitis/meningoencephalitis was also common (69.2%). Nearly half (46.2%) had both pulmonary and neurological disease. Cryptococcomas were frequent (76.9%); the majority were managed without surgical intervention. Severe impairment of consciousness at presentation and cerebrospinal fluid protein levels above 92.15 mg/dl were significantly associated with mortality. Amphotericin B deoxycholate plus fluconazole was the most prescribed induction regimen, with a median duration of 3 weeks. The overall mortality was 20.5%. Immune reconstitution inflammatory syndrome occurred only among patients with cryptococcomas and was managed with glucocorticoids in most cases. The performance of the cryptococcal antigen (CrAg) test was excellent in both neurological and pulmonary diseases. This study highlights the clinical spectrum of C. gattii complex infection and supports the potential utility of shorter induction regimens (< 4 weeks), as well as the role of CrAg as a valuable diagnostic tool.
