Search Results (226)

Invasive candidiasis (IC), characterized by the most common clinical manifestation of candidemia, is a fungal infection with a high mortality rate and a significant impact on global public health. It is estimated that each year there are between 227,000 and 250,000 hospitalizations related to IC, with more than 100,000 associated deaths. In Latin America and the Caribbean (LA&C), the absence of a standardized surveillance system has led to multicenter studies documenting incidences ranging from 0.74 to 6.0 cases per 1000 hospital admissions, equivalent to 50,000–60,000 hospitalizations annually, with mortality rates of up to 60% in certain high-risk groups. Armed conflicts and structural violence in LA&C cause forced displacement, the collapse of health systems, and poor living conditions—such as overcrowding, malnutrition, and lack of sanitation—which increase vulnerability to opportunistic infections, such as IC. Insufficient specialized laboratories, diagnostic technology, and trained personnel impede pathogen identification and delay timely initiation of antifungal therapy. Furthermore, the empirical use of broad-spectrum antibiotics and the limited availability of echinocandins and lipid formulations of amphotericin B have promoted the emergence of resistant non-albicans strains, such as Candida tropicalis, Candida parapsilosis, and, in recent outbreaks, Candidozyma auris. Full article

Background: Invasive fungal infections (IFIs) after liver transplantation (LT) remain a concern. No universal protocol for antifungal prophylaxis in LT exists. Antifungal prophylaxis varies across European centers. Studies suggest risk stratification for prophylaxis. This study assessed IFI frequency and outcomes in adult LT recipients without antifungal prophylaxis and evaluated risk stratification for predicting IFIs. Method: A retrospective analysis of clinical and microbiological data from 244 liver transplant patients focused on IFI within 100 days post-transplantation. Of these, 225 (92%) had right liver transplants from living donors. We assessed two risk stratification models for predicting IFI: one categorizes patients into low- and high-risk groups, and the other divides patients into three categories, with two eligible for prophylaxis and one not. Results: Of 244 patients, 3% (seven individuals) developed invasive fungal infections (IFI), including two aspergillosis and five candidiasis. IFI occurred in 8% of high-risk and 2% of low-risk patients in the first stratification, with no significant difference between groups (p = 0.144). In the second stratification, IFI was found in 4% of the target and 2% of non-target groups, without a significant difference (p = 0.455). Patients with IFI showed higher mean MELD scores of 21.71 ± 2.35 versus 17.04 ± 6.48 in those without IFI (p < 0.05). Conclusions: This study evaluated IFI outcomes without systemic antifungal prophylaxis in LT recipients. Limited antifungal use in a major living liver donor transplantation (LDLT) group, with low MELD scores and immunosuppression protocols, could be feasible. Future multicenter studies can improve understanding and develop prophylaxis algorithms for LT settings. Full article

Candidiasis is a major fungal infection worldwide, with invasive forms linked to high morbidity and mortality. The emergence of azole resistance in Candida parapsilosis causing candidemia led us to examine the epidemiology and antifungal susceptibility of Candida species at the University Hospital of Liège between January 2017 and December 2023. A total of 916 isolates from blood or sterile body fluids, tissues, and abscesses were analyzed. Species identification was performed using MALDI-TOF MS and antifungal susceptibility testing via Sensititre YO10 AST was interpreted according to the CLSI guidelines. Candida albicans remained the predominant species (56%), followed by Nakaseomyces glabratus (19%), Candida parapsilosis (8%), and Candida tropicalis (7%). No significant shift toward non-albicans Candida species (NAC) was observed even during the COVID-19 pandemic, supporting the use of narrow-spectrum empirical therapy in selected patients. Fluconazole susceptibility was high in C. albicans (98.8%), whereas N. glabratus and C. tropicalis showed high resistance rates with 10.1% and 16.9%, respectively. C. parapsilosis showed stable fluconazole susceptibility across the study period. Echinocandins demonstrated excellent activity (95.6–100%), and amphotericin B was effective against nearly all isolates. This seven-year surveillance at the University Hospital of Liège confirms that while C. albicans remains the predominant and highly susceptible species, rising azole resistance in non-albicans Candida—particularly N. glabratus and C. tropicalis—highlights the critical need for ongoing local epidemiological monitoring to guide effective and targeted antifungal therapy. Full article

Background/objectives: Candida albicans is a major fungal pathogen that poses a serious threat to immunocompromised individuals. The increasing prevalence of fluconazole-resistant strains presents a critical clinical challenge, emphasizing the urgent need for novel therapeutic strategies. This study aimed to evaluate the prophylactic potential of a new liposomal vaccine formulation, Tuft-lip-WCAgs, comprising Tuftsin and C. albicans whole cell antigens, in providing immune protection against systemic candidiasis. Methods: The vaccine formulation was tested in a murine model of systemic C. albicans infection. The efficacy of the Tuft-lip-WCAg vaccine was evaluated through a survival analysis, fungal burden assessments, and immunological profiling. Immune responses were assessed by measuring serum antibody titers and isotypes, T cell proliferation, and cytokine secretion (IFN-γ and IL-4) from splenocytes. Results: FLZ treatment showed weak antifungal activity, high MIC values, and limited biofilm disruption and failed to ensure long-term survival, resulting in 100% mortality by day 40. In contrast, Tuft-lip-WCAg vaccination was well tolerated and conferred complete protection, with no detectable fungal burden by day 40. Vaccinated mice exhibited significantly elevated total antibody titers (166,667 ± 14,434), increased IgG2a levels, and enhanced T cell proliferation (stimulation index: 3.9 ± 0.84). Splenocytes from immunized mice secreted markedly higher levels of IFN-γ (634 ± 128 pg/mL) and IL-4 (582 ± 82 pg/mL), indicating a balanced Th1/Th2 immune response. Tuft-lip-WCAg vaccination also achieved 100% survival and the lowest kidney fungal burden (556 ± 197 CFUs/g). Conclusions: Tuft-lip-WCAg formulation is a safe, immunogenic, and highly effective vaccine candidate that offers complete protection against drug-resistant C. albicans in a murine model. These findings support its promise as a novel immunoprophylactic strategy, particularly for immunocompromised populations at high risk of invasive candidiasis. Full article

Candidemia is a significant cause of morbidity and mortality among critically ill patients. Early-onset candidemia is characterized by occurring within the first seven days after admission to the Intensive Care Unit and presents several important challenges regarding its management. Risk factors may vary among patients with early- and late-onset infection, while clinical manifestations are generally non-specific and covered by the underlying disease and co-morbidities. Diagnosis and appropriate therapy are frequently delayed, with a high risk of progression to invasive, deep-seated infections, leading to rapid clinical deterioration. Management strategies to optimize the approach for patients with early-onset candidemia include the use of both conventional and novel diagnostic techniques, the initiation of appropriate antifungal therapy, administration of an adequate dose, daily evaluation of clinical response, de-escalation treatment whenever possible, and early discontinuation. Incorporating an antifungal stewardship program in clinical practice is essential in order to achieve the best clinical outcomes. Based on a review and analysis of the available literature, this article provides a thorough update on the risk factors, clinical characteristics, diagnostic methods, and management of early-onset candidemia in adult critically ill patients. Full article

The World Health Organization (WHO) prioritized 19 fungal species based on the significant impact of these pathogens on human health, including the emergence of antifungal resistance, which highlights the necessity of finding new antifungal therapies. Among these novel therapeutic approaches, the antimicrobial pore-forming peptide C14R has shown to be promising against Candida albicans and Candida auris. In this study, the antifungal in vitro efficacy of C14R was assessed against six additional species from the WHO priority list, Cryptococcus neoformans, Cryptococcus gattii, Candida glabrata, Candida tropicalis, Candida parapsilosis and Candida krusei, as well as against Candida dubliniensis. This study shows that C14R has good antifungal activity against several clinical isolates of the studied species, with MIC values between 0.8476 and 10.88 µg/mL. Most notably, some of the studied isolates are resistant to commonly used antifungal drugs but are susceptible to the peptide. C14R showed, moreover, its capacity to disrupt Cryptococcus capsules, beyond its already proven capacity to disrupt plasma membranes, and its antifungal activity was not affected depending on the serotype or species assessed. The inclusion of basidiomycete and ascomycete yeasts allowed us to display the broad-spectrum potential of C14R, highlighting it as a promising candidate as an antifungal agent. Full article

Invasive candidiasis represents a major global health concern, with incidence and mortality rates expected to rise due to medical advancements and unavoidable risk factors. This retrospective, multicentric study was conducted in eight hospitals in a northeastern Italian region, enrolling adult patients diagnosed with candidemia from 1 January 2018 to 31 December 2022. Epidemiological trends and clinical characteristics were analyzed and compared to those from a prior regional study (2009–2011), allowing a fourteen-year comparative evaluation. A shift in species distribution was observed, with a decline in Candida albicans (from 65.7% to 57.8%) and a rise in non-albicans species, particularly the Candida parapsilosis complex (from 16.1% to 18.2%). Guideline adherence was assessed applying the EQUAL Candida score; scores ≥ than 11.5 were independently associated with improved in-hospital survival (HR 3.51, p < 0.001). Among individual score components, empiric echinocandin therapy and central venous catheter removal correlated with better outcomes. Centers with routine infectious disease (ID) consultations showed higher survival and adherence, reinforcing the value of specialist involvement. These findings support local epidemiological and management practice surveillance program adoption to address context-specific gaps, promote the adoption of best practices in Candida BSI management—as expanded ID specialist consultations and education programs—and, ultimately, reduce candidemia-related mortality rates. Full article

Coinfection rates of candidiasis in patients affected by COVID-19 had a significantly increase during the sanitary contingency. The objective of this scoping review is to analyze the available scientific evidence around the coinfection of invasive candidiasis in hospitalized patients with severe COVID-19 disease. Online databases such as PubMed, EBSCO, SciFinder, Scopus, and SciELO were used to analyze the different scientific studies published from January 2020 to December 2022, selecting 48 publications that reported comorbidity between invasive candidiasis and COVID-19 as a study variable. Based on the PRISMA-ScR extension for scoping reviews, we identified more than half of the publications (57%) as observational, descriptive, and analytic studies, while 43% were systematic reviews. Overall, up to 169,468 adult patients admitted to the intensive care unit were examined. Coinfection was due mainly to Candida albicans (75%), but some more species were reported such as Meyerozyma parapsilosis (formerly Candida parapsilosis); Meyerozyma guilliermondii (formerly Candida guilliermondii); Nakaseomyces glabratus (formerly Candida glabrata); Candida tropicalis; Candida dubliniensis; Clavispora lusitaniae (formerly Candida lusitaniae); and Pichia kudriavzevii (formerly Candida krusei). We concluded that patients infected by SARS-CoV-2 had a higher incidence of fungal coinfections, thus increasing the mortality rate, disease severity, and length of hospital stay in the intensive care unit. Full article

Intra-abdominal candidiasis (IAC), with or without candidemia, is a common condition in patients in intensive care units (ICUs). Early diagnosis of IAC remains a challenge for clinicians despite new biomarkers. Early and appropriate antifungal treatment, which is associated with better clinical outcomes, is negatively affected by the increased isolation of non-albicans Candida strains that are resistant to the commonly used azoles and echinocandins. Based on the pharmacokinetic (PK) and pharmacodynamic (PD) properties of the different treatment options, liposomal amphotericin B, rezafungin or high doses of anidulafungin appear to be the most appropriate first-line options for complicated IAC in ICUs. Full article

Background/Objectives: Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disorder with a recognized potential for malignant transformation. While histopathological examination remains the diagnostic gold standard, mucoscopy has emerged as a valuable non-invasive tool for assessing striae patterns, vascular features, and pigmentary alterations. This study aimed to evaluate the mucoscopic characteristics of OLP across different oral mucosal sites and to compare them with other inflammatory oral conditions, assessing their diagnostic relevance. Methods: A retrospective comparative study was conducted on 106 patients, including 33 with histopathologically confirmed OLP and 73 with other inflammatory oral conditions (pemphigus vulgaris, chronic cheilitis, hyperplastic oral candidiasis, leukoplakia, squamous cell carcinoma, pachyonychia congenita, morsicatio buccarum). Mucoscopic evaluation focused on the buccal mucosa, vermilion, and lingual mucosa. Features assessed included background color, white striae patterns, vascular morphology, the presence of erosions, and other features like blunting of the lingual papillae and scales on the vermilion. Statistical analysis was carried out using SPSS 29.0. Results: Reticular striae were highly specific to OLP, particularly on the buccal mucosa (90.9%, p < 0.001). Leukoplakia-like lesions were most prevalent on the lingual mucosa and significantly associated with dotted (p = 0.027) and looped vessels (p = 0.002). Erosions correlated significantly with both dotted (p < 0.001) and linear vessels (p = 0.011), especially in lingual and vermilion lesions. In comparison, control group lesions displayed significantly more globular structures (p < 0.001), veil-like patterns (p < 0.001), and diffuse vascular distributions (p = 0.018), particularly in cheilitis and candidiasis cases. Conclusions: Mucoscopy reveals distinct site-specific patterns in OLP, supporting its role as a non-invasive diagnostic aid. Comparative analysis highlights its utility in differentiating OLP from other inflammatory oral conditions and in identifying lesions with features suggestive of malignant potential. These findings support the integration of mucoscopy into routine clinical practice and warrant further validation through larger, prospective studies. Full article

Candidiasis belongs to common fungal infections and is usually mild and self-limiting. However, in patients with immunodeficiencies, it can transform into invasive infections with high mortality. Long-term antifungal treatment can lead to the emergence of resistance. The problem is further complicated by the development of fungal biofilm resistant to conventional antimicrobials. Due to a limited choice of available antifungals, the development of novel active agents, such as antimicrobial peptides (AMPs), is highly desirable. Human cathelicidin LL-37 is an intensively studied AMP with a confirmed broad spectrum of antimicrobial activities. Due to the relatively high costs of production, the design of shorter analogs of LL-37 has been recommended. In this study, we synthesized a KR12 amide, KRIVQRIKDFLR-NH₂, and its 24 derivatives obtained by substitution with fatty acids. The compounds were tested for their antifungal potential. They exhibited activity against the Candida albicans, C. glabrata, C. tropicalis and C. lipolytica. Five compounds: C₁₀-KR12-NH₂, C₁₂-KR12-NH₂, C₁₄-KR12-NH₂, 2-butyloctanoic acid-KR12-NH₂, and 4-phenylbenzoic acid-KR12-NH₂ were highly active against planktonic cells. C₁₄-KR12-NH₂ demonstrated also activity against C. albicans biofilm cultured on polystyrene for 24, 48 and 72 h. Lipidation has proven to be an effective strategy for improving microbiological activity of the KR12-NH₂ peptide. Full article

Invasive fungal infections in the intensive care unit (ICU) are not uncommon and most cases are caused by Candida species, specifically Candida albicans. However, recently, there has been an increase in non-albicans Candida spp. (C. glabrata; C. parapsilosis) causing invasive fungal infections. This has led to an increasing awareness of this infection due to the increase in documented antifungal resistance in many of these Candida species. In addition, manifestations of invasive candidiasis are often non-specific, and the diagnosis remains extremely challenging. Unfortunately, delays in antifungal therapy continue to hamper the morbidity; length of stay; and the mortality of these infections. Although the echinocandins are the drugs of choice in these infections, antifungal resistance among the non-albicans species (C. glabrata; C. krusei; C. auris; C. parapsilosis) is being observed more frequently. This has led to an increase in morbidity and mortality, specifically in critically ill patients. Overall, the diagnosis and management of invasive candidiasis in the ICU remain challenging. It is imperative that the critical care physician keeps this infection at the forefront of their differential diagnosis in order to decrease the mortality rate of these individuals. In this review, we discuss the current epidemiologic trends, diagnosis, and management of invasive candidiasis in the intensive care unit setting. Full article

Candidemia and invasive candidiasis represent critical healthcare-associated fungal infections that pose substantial challenges to medical systems worldwide. These conditions arise when fungi from the Candida genus infiltrate the bloodstream or deeper tissues, leading to a range of clinical manifestations. Among the various species, Candida albicans continues to hold its position as the most frequently encountered causative agent, largely due to its prevalence and adaptability within human hosts. However, it is far from the only significant player; other Candida species, such as Candida glabrata, Candida parapsilosis, and the particularly concerning Candida auris, contribute significantly to the disease burden and exhibit varying dominance depending on geographic regions. The clinical presentation of these infections can differ widely, spanning from subtle, almost imperceptible symptoms in some patients to severe, life-threatening fulminant sepsis in others, often accompanied by alarmingly high mortality rates that underscore the urgency of effective management strategies. Several well-established risk factors predispose individuals to developing invasive candidiasis and candidemia. Breaches in the body’s natural barriers—such as the skin (cutaneous) or the gastrointestinal (GI) tract—provide entry points for these opportunistic pathogens. Additionally, deficiencies in the host’s immune responses, whether due to medical treatments, underlying diseases, or genetic predispositions, heighten vulnerability to infection. Among the diverse Candida species, Candida auris has emerged as an especially troubling entity in recent years. This multidrug-resistant species is notorious for its resistance to standard antifungal therapies, which complicates treatment efforts and contributes to elevated morbidity and mortality rates. Its rapid global spread has positioned it as a formidable public health threat, prompting heightened surveillance and research into its behavior and control. Full article

Candida albicans (C. albicans) is a major opportunistic fungal pathogen that causes life-threatening infections, particularly in immunocompromised individuals, underscoring the critical need to understand its pathogenic mechanisms. This study investigates the role of Cas5, a key transcription factor, in regulating C. albicans cell wall remodeling, virulence, and host interactions. Genetic manipulation and biochemical assays were used to examine the effects of Cas5 depletion on C. albicans cell wall structure, adhesion to host cells, morphology transition, innate immune cells recruitment, and pathogenicity in a BALB/C mouse model of oropharyngeal candidiasis (OPC). The results showed that the Cas5 depletion mediated β-glucan exposure and enhanced C. albicans’s ability to recruit neutrophils in vivo. Additionally, Cas5-mediated changes in cell surface hydrophobicity (CSH), CWP expressions, and morphological transition promoted C. albicans adhesion to biologically active surfaces (host cells) and increased fungal burden in the mouse model of OPC. In conclusion, Cas5 modulates C. albicans cell wall remodeling by masking cell wall β-glucan, altering CSH, and regulating the expression of cell wall proteins (CWPs). Additionally, Cas5 participates in inhibiting neutrophil recruitment and enhancing the C. albicans adhesion to host cells, as well as facilitating morphological transitions. These actions promote the colonization and invasion of C. albicans in OPC pathogenesis. Full article

Molecular techniques recently integrated the candidiasis diagnostic workflow, avoiding the culture-based prolonged turn-around time and lack of sensitivity. The present retrospective study evaluated the OLM CandID Real-Time PCR on serum samples in the early and rapid candidaemia diagnosis among ICU patients. The final purpose of the protocol was to demonstrate the effectiveness of a PCR assay in the invasive candidiasis diagnostic workflow due to the high sensitivity rates and species identification possibility. The evaluation screened 60 suitable patients, accounting for 10 probable and 7 proven candidiasis cases. Patients with at least a positive (1→3)-β-D-glucan (BDG) value underwent molecular procedures. A sensitivity of 83.3%, a specificity of 94.3%, a positive predictive value of 87.5%, and a negative predictive value of 91.7% emerged for the PCR assay. As a conclusion, Candida PCR assays may represent useful diagnostic assistance tools when applied together with serological markers and culture-based assays. Full article