Search Results (58)

Background: Polymerase chain reaction (PCR) is highly sensitive and specific for the rapid diagnosis of invasive fungal disease (IFD) but is not yet widely implemented due to concerns regarding limited standardisation between assays, the lack of commercial options and the absence of clear guidance on interpreting results. Objectives and Methods: This review provides an update on technical and clinical aspects of PCR for the diagnosis of the most pertinent fungal pathogens, including Aspergillus, Candida, Pneumocystis jirovecii, Mucorales spp., and endemic mycoses. Summary: Recent meta-analyses have demonstrated that quantitative PCR (qPCR) offers high sensitivity for diagnosing IFD, surpassing conventional microscopy, culture and most serological tests. The reported specificity of qPCR is likely underestimated due to comparison with imperfect reference standards with variable sensitivity. Although the very low limit of detection of qPCR can generate false positive results due to procedural contamination or patient colonisation (particularly in pulmonary specimens), the rates are comparable to those observed for biomarker testing. When interpreting qPCR results, it is essential to consider the pre-test probability, determined by the patient population, host factors, clinical presentation and risk factors. For patients with low to moderate pre-test probability, the use of sensitive molecular tests, often in conjunction with serological testing or biomarkers, can effectively exclude IFD when all tests return negative results, reducing the need for empirical antifungal therapy. Conversely, for patients with high pre-test probability and clinical features of IFD, qPCR testing on invasive specimens from the site of infection (such as tissue or bronchoalveolar lavage fluid) can confidently rule in the disease. The development of next-generation sequencing methods to detect fungal infection has the potential to enhance the diagnosis of IFD, but standardisation and optimisation are essential, with improved accessibility underpinning clinical utility. Full article

Aspergillus spp., particularly A. fumigatus, are increasingly reported as emerging pathogens in cetaceans, yet their clinical and ecological relevance remains poorly characterized. This systematic review synthesizes evidence from 34 studies involving 106 animals, identifying respiratory, neurological, and otic infections as the most frequent presentations with potential interspecies tropism. Invasive disease, frequently fatal, was linked to co-infections—especially with morbillivirus—and environmental stressors such as pollution- and climate-related immune suppression. Despite cetaceans’ role as sentinel species, antifungal susceptibility testing and species-level identification were inconsistently performed. Additionally, azole-resistant A. fumigatus strains were isolated from wild porpoises, indicating environmental antifungal exposure and potential public health implications. Aspergillosis remains underdiagnosed in free-ranging populations, particularly in remote or pelagic species. Conservation implications were scarcely addressed, despite evidence suggesting that fungal disease may contribute to morbidity, stranding, and population impact. This review underscores the need for enhanced surveillance, integrative diagnostics, and recognition of fungal pathogens in a One Health framework. The growing intersection of climate change, emerging mycoses, and wildlife conservation positions Aspergillus infections in cetaceans as both a marine mammal health concern and an ecological indicator of broader environmental changes. Full article

Invasive candidiasis is a common fungal infection associated with multiple risk factors, such as cancer, neutropenia, corticosteroid therapy, catheterization, and the use of broad-spectrum antibiotic treatment. Candida albicans is the predominant causative agent, although other Candida species have been emerging in the last years, together with a rise in a number of strains resistant to the currently available antifungal drugs, which poses a challenge when treating these infections. Drug repurposing and drug combinations are promising strategies for the treatment of invasive mycoses. In this study, we evaluated the effect of the combination of fluconazole (FLZ) and cyclosporine A (CsA) against 39 clinical isolates and reference strains of Candida. Two methods, the Loewe additivity model and Bliss independence model, were used to assess the antifungal activity of the drug combination according to CLSI and EUCAST guidelines. The results demonstrated a synergistic effect between fluconazole (FLZ) and cyclosporine A (CsA) against 15–17 Candida isolates, depending on the evaluation model used, including FLZ-resistant strains of C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis. Notably, the combination significantly reduced the minimum inhibitory concentration (MIC) of FLZ in a substantial number of isolates, including those with resistance to FLZ. Additionally, time–kill curve studies confirmed the synergistic interaction, further validating the potential of this combination as an alternative therapeutic strategy for candidiasis treatment. These findings emphasize the importance of investigating innovative drug combinations to address the challenges posed by antifungal resistance and improve treatment options for invasive fungal infections. Full article

Aspergillus spp. are ubiquitous fungi present in soil, organic debris, water, decaying vegetation and dust produced in renovation and/or building work. Several studies have shown the presence of aspergilli in various healthcare environments. Typically, thousands of fungal spores are inhaled every day, but if spore clearance fails (typically in immunocompromised patients), fungi can grow and invade lung tissue, causing invasive aspergillosis (IA) which is one of the most frequent infections in highly immunocompromised patients. Aspergillus fumigatus is the most common species involved; this species can be attributed to about 80% of the cases of aspergillosis. According to the WHO, Aspergillus fumigatus is one of four critical priority fungi. The first-line treatment of diseases caused by Aspergillus, in particular IA, is based on triazole antimycotics. Unfortunately, resistance to antimycotics is increasing, partly due to their widespread use in various areas, becoming a significant concern to clinicians who are charged with caring for patients at high risk of invasive mycoses. A recent WHO report emphasised the need for strategies to improve the response, and in particular strengthen laboratory capacity and surveillance, support investment in research and strengthen public health interventions for the prevention and control of fungal infections through a One Health approach. Full article

Although advances in the management of pediatric neoplasms have profoundly improved infectious disease outcomes, invasive fungal diseases (IFDs) remain a major cause of morbidity and mortality in children and adolescents with high-risk hematological malignancies. A retrospective study was conducted in the Pediatric Hematology–Oncology Department of the University General Hospital of Heraklion for 2013–2022 to estimate the prevalence and describe the clinical and epidemiological characteristics of IFDs for pediatric and adolescent patients with neoplasia. Demographic, clinical, and laboratory parameters were analyzed to identify risk factors for the development of IFD. The overall prevalence of IFDs was estimated to be 7.8% (12/154 patients) throughout the study. The mean age at IFD diagnosis was 9.8 years (SD 6.4 years). The most common IFD was possible/probable invasive pulmonary aspergillosis (IPA; in ≈50%), followed by candidemia/invasive candidiasis (in 44%). Candida parapsilosis was the most prevalent Candida species (4/6 events). Of interest, the majority (75%) of IFDs were breakthrough infections. Patients with increased risk for IFDs were those who were colonized by fungi in sites other than the oral cavity, hospitalized in the intensive care unit for >7 days, received >7 different antimicrobials in the last 3 months, or had severe neutropenia for >44 days. Two children out of a total of 12 with IFD died due to refractory disease or relapse (16.7%). More detailed and prospective epidemiological studies on fungal infections in pediatric patients with hematological or solid neoplasms can contribute to the optimization of prevention and treatment. Full article

Invasive fungal diseases (IFDs) comprise a growing healthcare burden, especially given the expanding population of immunocompromised hosts. Early diagnosis of IFDs is required to optimise therapy with antifungals, especially in the setting of rising rates of antifungal resistance. Molecular techniques including nucleic acid amplification tests and whole genome sequencing have potential to offer utility in overcoming limitations with traditional phenotypic testing. However, standardisation of methodology and interpretations of these assays is an ongoing undertaking. The utility of targeted Aspergillus detection has been well-defined, with progress in investigations into the role of targeted assays for Candida, Pneumocystis, Cryptococcus, the Mucorales and endemic mycoses. Likewise, whilst broad-range polymerase chain reaction assays have been in use for some time, pathology stewardship and optimising diagnostic yield is a continuing exercise. As costs decrease, there is also now increased access and experience with whole genome sequencing, including metagenomic sequencing, which offers unparalleled resolution especially in the investigations of potential outbreaks. However, their role in routine diagnostic use remains uncommon and standardisation of techniques and workflow are required for wider implementation. Full article

Human mycoses cover a diverse field of fungal diseases from skin disorders to systemic invasive infections and pose an increasing global health problem based on ineffective treatment options, the hampered development of new efficient drugs, and the emergence of resistant fungal strains. Niclosamide is currently applied for the treatment of worm infections. Its mechanisms of action, which include the suppression of mitochondrial oxidative phosphorylation (also known as mitochondrial uncoupling), among others, has led to a repurposing of this promising anthelmintic drug for the therapy of further human diseases such as cancer, diabetes, and microbial infections. Given the urgent need to develop new drugs against fungal infections, the considerable antifungal properties of niclosamide are highlighted in this review. Its chemical and pharmacological properties relevant for drug development are also briefly mentioned, and the described mitochondria-targeting mechanisms of action add to the current arsenal of approved antifungal drugs. In addition, the activities of further salicylanilide-based niclosamide analogs against fungal pathogens, including agents applied in veterinary medicine for many years, are described and discussed for their feasibility as new antifungals for humans. Preliminary structure–activity relationships are determined and discussed. Various salicylanilide derivatives with antifungal activities showed increased oral bioavailabilities when compared with niclosamide. The simple synthesis of salicylanilide-based drugs also vouchsafes a broad and cost-effective availability for poorer patient groups. Pertinent literature is covered until 2024. Full article

Many infectious diseases are transmitted via the air and are, therefore, particularly difficult to combat. These infections include various invasive mycoses caused by molds. The usual route of infection is the inhalation of conidia. In hospitals, infection can also occur through the deposition of conidia in otherwise sterile anatomical sites during surgical and other invasive procedures. Therefore, knowledge of airborne mold concentrations can lead to measures to protect patients from fungal infections. The literature on this topic contains insufficient and sometimes ambiguous information. This is evidenced by the fact that there are no international recommendations or guidelines defining the methodology of air sampling and the interpretation of the results obtained. Surgical departments, intensive care units and medical mycology laboratories are, therefore, left to their own devices, leading to significant differences in the implementation of mycological surveillance in hospitals. The aim of this mini-review is to provide an overview of the current methods of air sampling and interpretation of results used in medical mycology laboratories. Full article

Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin. Inhibition of Mucorales fungi by allicin in solution and by allicin vapor was demonstrated. Mathematical modeling showed that the efficacy of allicin vapor is comparable to direct contact with the commercially available antifungal agent amphotericin B (ampB). Furthermore, the study revealed a synergistic interaction between allicin and the non-volatile ampB. The toxicity of allicin solution to human cell lines was evaluated and it was found that the half maximal effective concentration (EC₅₀) of allicin was 25–72 times higher in the cell lines as compared to the fungal spores. Fungal allicin sensitivity depends on the spore concentration, as demonstrated in a drop test. This study shows the potential of allicin, a sulfur-containing defense compound from garlic, to combat zygomycete fungi. The findings underscore allicin’s promise for applications in infections of the nasopharynx via inhalation, suggesting a novel therapeutic avenue against challenging fungal infections. Full article

In 2019, the bark beetle Ips amitinus (native to central Europe) was identified in south-western Siberia at a distance exceeding 2500 km east of its previously known easternmost location in the European part of Russia. In Siberia, its invasive populations are characterised by high abundance and harmfulness. Here, I. amitinus accomplishes primary attacks on standing vital trees of Pinus sibirica with a lethal outcome. This invasion has already resulted in massive dieback in stands of pine over a large geographic territory. By, 2021, the invaded area was estimated to cover at least 31,200 km². The objectives of this study were to investigate fungi associated with/vectored by I. amitinus in its invasive area in south-western Siberia and wood decay fungi that cause root and butt rots to P. sibirica. This led to the following conclusions: (i) DNA analysis of sixty adult beetles of Ips amitinus collected from P. sibirica in south-west Siberia revealed the presence of 143 fungal taxa; (ii) species richness was significantly higher in beetles collected from dead branches than from (more recently infested) dying branches; (iii) fungal communities were >90% dominated by yeasts, among which the most common were Nakazawaea holstii, Kuraishia molischiana, and N. ambrosiae; (iv) entomopathogenic Beauveria bassiana s.l. was the most common fungus isolated from dead/mycosed beetles of I. amitinus, followed by Lophium arboricola and four Ophiostoma spp.; and (v) Heterobasidion parviporum was the most common decay fungus detected, which was causing heart rot in stems of P. sibirica. Full article

Iron plays an important role in the pathogenesis of infections, including invasive fungal infections (IFIs). Studies suggested that iron overload might represent an additional risk factor for IFIs among patients with hematological malignancies. We conducted a prospective, multi-center study amongst adult patients with newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in transformation to determine whether baseline iron overload as measured using the bone marrow iron store (BMIS) score is an independent risk factor for the development of IFIs. We also measured baseline serum iron and ferritin levels. A total of 98 patients were enrolled (76 with AML) and were followed for 12 months. Twenty-two patients developed IFI during the follow-up period (invasive aspergillosis n = 16, candidemia n = 5, mucormycosis n = 1). A baseline BMIS score ≥ 3 indicated that iron overload was relatively common (38/98 patients, 38%), and its frequency was comparable between patients with no IFIs (31/76, 40.7%) and in those with IFIs (8/22, 36.4%). Univariate analysis showed that only the presence of AML was associated with increased risk for IFIs [OR (95% CI) 7.40 (1.05–325.42)]. Both univariate and multivariate analyses showed that an increased BMIS score (≥3) at baseline was not an independent risk factor for IFIs. Similarly, there was no difference in serum iron and ferritin between the two groups that had similar demographic characteristics. Indices of iron overload were not independent risk factors for IFIs in our cohort of Greek patients with newly diagnosed AML/MDS in transformation. Full article

Candida auris is an emerging fungal pathogen responsible for hospital outbreaks of invasive candidiasis associated with high mortality. The treatment of these mycoses is a clinical challenge due to the high resistance levels of this species to current antifungal drugs, and alternative therapeutic strategies are needed. In this study, we evaluated the in vitro and in vivo activities of combinations of citral with anidulafungin, amphotericin B or fluconazole against 19 C. auris isolates. The antifungal effect of citral was in most cases similar to the effect of the antifungal drugs in monotherapy. The best combination results were obtained with anidulafungin, with synergistic and additive interactions against 7 and 11 of the 19 isolates, respectively. The combination of 0.06 μg/mL anidulafungin and 64 μg/mL citral showed the best results, with a survival rate of 63.2% in Caenorhabditis elegans infected with C. auris UPV 17-279. The combination of fluconazole with citral reduced the MIC of fluconazole from > 64 to 1–4 μg/mL against 12 isolates, and a combination of 2 μg/mL fluconazole and 64 μg/mL citral was also effective in reducing mortality in C. elegans. Amphotericin B combined with citral, although effective in vitro, did not improve the activity of each compound in vivo. Full article

Critically ill COVID-19 patients requiring mechanical ventilation in the intensive care unit are at risk of developing invasive candidiasis. In this study we aimed to (1) characterize oral cultivable mycobiota of mechanically ventilated adult COVID-19 patients in an ICU setting by sampling four distinct oral niches in two fixed time points with regards to oral health status, (2) investigate Candida spp. infections in this population, and (3) compare oral mycobiota with selected bacteriobiota strains during the observation in the ICU. We recruited 56 adult COVID-19 patients who qualified for mechanical ventilation. Patients received either standard or extended oral care procedures with tooth brushing. Oral samples were taken first within 36 h and after 7 days of intubation. Yeast-like fungi were identified by MALDI/TOF mass spectrometry. Yeast infection cases were retrospectively analyzed. Candida spp. in oral sampling was identified in 80.4% and 75.7%, C. albicans in 57.1% and 61.1%, and non-albicans Candida species in 48.2% and 47.2% patients at baseline and follow-up, respectively. There were no differences in the overall CFU counts of Candida spp. species and individual Candida species in oral samples, both at baseline and follow-up. At baseline, a higher prevalence of Candida spp. was associated with a higher identification rate of Lactobacillus spp. (64.4% vs. 27.3%, p = 0.041). At follow-up, there was a borderline lower prevalence of Candida spp. in patients with Lactobacillus spp. identified (57.1% vs. 87.0%, p = 0.057). The incidence rate of candidiasis was 5.4% and the incidence density was 3.1/1000 pds. In conclusion, non-albicans Candida species in oral samples were identified in nearly half of patients. Oral health was moderately impaired. A high incidence of yeast infections, including invasive cases, in patients hospitalized in the ICU due to COVID-19 and requiring mechanical ventilation was noted. Severe COVID-19 and disease-specific interventions within the ICU possibly played a major role promoting Candida spp. infections. Full article

Turtles and ‘tortoises’ populations are declining in number, the factors driving extinction risks being related to habitat loss and degradation, climate change, introduction of invasive plant and animal species, consumption by humans for food and medicinal use, and collection for international pet trade. Fungal infections represent one of the main threats for ecosystem health. The present narrative review deals with conventional and emerging mycoses of Chelonians. Although conventional mycoses in captive and pet reptiles would depend on poor husbandry, being the agents mostly opportunistic pathogens, some fungal species were reported to occur more frequently, such as the entomopathogen Purpureocillium lilacinum. Furthermore, emerging agents such as the Fusarium solani species complex have been recognized as a real threat for the surviving of some aquatic species, acting as primary pathogens. This complex has been recently included within pathogens in One Health issues. Emydomyces testavorans is recognized as an emerging threat, although, due its recent identification, information about its epidemiology is limited. Data about treatments and outcomes of mycoses in Chelonians are also referred. Full article

The role of empiric antifungals for post-surgical abscesses (PSAs) is controversial, and international guidelines on invasive mycoses focus on bloodstream infections. We analyzed a retrospective cohort of 319 patients with PSA at a tertiary-level hospital in Italy during the years 2013–2018. Factors associated with empiric antifungal administration were analyzed and compared with factors associated with fungal isolation from the abdomen. Forty-six patients (14.4%) received empiric antifungals (65.2% azoles). Candida was isolated in 34/319 (10.7%) cases, always with bacteria. Only 11/46 patients receiving empirical antifungals had abdominal Candida. Only 11/34 patients with a fungal isolate received empiric antifungal therapy. Upper GI surgery (OR: 4.76 (CI: 1.95–11.65), p = 0.001), an intensive care unit stay in the previous 90 days (OR: 5.01 (CI: 1.63–15.33), p = 0.005), and reintervention within 30 days (OR: 2.52 (CI: 1.24–5.13), p = 0.011) were associated with empiric antifungals in a multivariate analysis, while pancreas/biliary tract surgery was associated with fungal isolation (OR: 2.25 (CI: 1.03–4.91), p = 0.042), and lower GI surgery was protective (OR: 0.30 (CI: 0.10–0.89), p = 0.029) in a univariate analysis. The criteria for empiric antifungal therapy in our practice seem to be inconsistent with the risk factors for actual fungal isolation. Better guidance for empiric therapy should be provided by wider studies. Full article