Invasive candidiasis (IC) is a severe infection primarily affecting immunocompromised patients and is associated with high mortality and substantial hospital costs. Accurate regional data on epidemiology and antifungal resistance of IC are crucial for effective clinical management. The China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study is a laboratory-based multicenter study initiated in August 2009. This report presented updated data from August 2017 to December 2021, involving 76 hospitals across 28 provincial regions in China, and included a 12-year longitudinal analysis. Isolates from patients with IC were assigned to species level by matrix-assisted laser desorption ionization-time of flight mass spectrometry and internal transcribed spacer rDNA sequencing. Susceptibility testing was performed for nine antifungal agents using the broth microdilution method. A total of 11,679 Candida isolates were collected. Candida albicans was the most common Candida species (46.0%), followed by Candida tropicalis (17.6%), Candida parapsilosis sensu stricto (15.6%), and Candida glabrata sensu stricto (11.2%). Antifungal resistance rates showed notable variations among different Candida species, with the highest azole resistance observed in C. tropicalis isolates causing candidemia (42.5% to fluconazole and 38.9% to voriconazole). Cross- and multi-drug resistance to azoles and echinocandins was observed in all predominant Candida species. The species distribution of major Candida pathogens causing IC remained stable in China, while antifungal resistance increased, especially among non-albicans Candida species. Enhanced surveillance, accurate species identification, and strengthened antifungal stewardship are needed to address the growing challenge of antifungal resistance.

Invasive candidiasis is a fungal infection characterized by a high mortality rate. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family receptors play a crucial role in regulating innate responses of both leukocytes and epithelia. Human CEACAM3, CEACAM5 and CEACAM6 receptors recognize Candida albicans and are expressed in transgenic CEABAC10 mice. In a murine C. albicans infection model, CEABAC10 mice exhibited a shortened survival period attributed to an early cytokine storm, an exacerbated acute phase response, and heightened systemic inflammation compared to their wild-type littermates. The livers and kidneys of CEABAC10 mice displayed intensified purulent necrotizing inflammation, accompanied by increased infiltration of neutrophils and macrophages. Our in vivo and in vitro data indicated that the expression of CEACAM6 on monocytes of CEABAC10 mice caused the elevated cytokine levels and the subsequent exacerbation of the acute phase response upon C. albicans infection, resulting in decreased survival.

Introduction Candida glabrata is the second leading cause of invasive candidiasis worldwide and represents a major clinical challenge due to its intrinsic antifungal resistance, stress tolerance, and ability to persist in hostile host environments. We report a complex case of multidistrict C. glabrata infection in a 39-year-old immunocompetent male who presented with septic shock secondary to gastric perforation and thoracic contamination. Despite guideline-recommended echinocandin therapy, persistent fungal growth was detected in multiple anatomical compartments, including bloodstream, pleural fluid, surgical wound, and bronchoalveolar lavage samples. Methods Serial cultures and antifungal susceptibility testing were performed using MALDI-TOF MS and interpreted according to CLSI criteria. Radiological monitoring, surgical source control, and pharmacokinetic considerations guided therapeutic decisions. Results C. glabrata isolates showed reduced azole susceptibility but remained susceptible to echinocandins and amphotericin B. Persistent fungal growth between postoperative day (POD) 8 and POD 16 prompted escalation from caspofungin to micafungin and subsequently to combination therapy with liposomal amphotericin B. Rapid clinical improvement followed initiation of dual therapy, with microbiological clearance by POD 20 and complete recovery by POD 30. Conclusion This case highlights the challenges of treating multidistrict Candida glabrata infections and underscores the potential role of echinocandin–liposomal amphotericin B combination therapy when pharmacokinetic barriers may limit the effectiveness of antifungal monotherapy.

Invasive candidiasis is a severe opportunistic infection whose incidence may be influenced by major disruptive events. The COVID-19 pandemic substantially altered hospital dynamics in Colombia. This study aimed to evaluate temporal trends, seasonality, and potential changes in the incidence of invasive candidiasis between 2019 and 2024. We conducted an observational time-series study using confirmed cases of invasive candidiasis from medium- and high-complexity hospitals in three major Colombian cities. Cases were aggregated quarterly. An interrupted time-series (ITS) analysis was performed. A total of 1294 cases were analyzed. An increasing trend was observed until mid-2022, followed by a decline during 2023. Seasonal decomposition revealed persistent seasonality with recurrent peaks in the second and fourth quarters. The ITS analysis did not demonstrate statistically significant changes in level or slope after the interruption (p > 0.05), although clinically relevant fluctuations were observed. No significant differences in temporal trends were identified across Candida species. Invasive candidiasis in Colombia exhibited a complex temporal evolution during and after the COVID-19 pandemic characterized by sustained seasonality and an increase followed by a decline. Although the ITS analysis did not identify statistically significant post-pandemic changes, the findings support the use of time-series models as valuable tools for epidemiological surveillance and trend monitoring.

Invasive gastric candidiasis presenting as gastric perforation in an immunocompetent adult: a rare case report

Candida auris, a significant pathogen causing invasive candidiasis with high mortality rates and frequent hospital outbreaks, is understudied in Malaysia. This study retrospectively examined invasive candidiasis cases at Universiti Malaya Medical Centre from 2018 to 2021. Four C. auris strains were isolated from blood and peritoneal samples of intensive care unit patients and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antifungal susceptibility testing using Sensititre™ YeastOne YO10 plate showed resistance to amphotericin B (2-4µg/ml) and fluconazole (256µg/ml) but susceptibility to echinocandins. Whole-genome sequencing revealed a 12.31Mb genome, 45.59% G + C content, 99.95-99.99% average nucleotide identity between the isolates, and 190-225 single nucleotide polymorphisms. The Malaysian strains were phylogenetically related to the South Asian Clade (I) and harbored mutations associated with resistance to fluconazole (ERG11 gene: Y132F; CDR1 gene: E709D) and amphotericin B (ERG2 gene: E39D). The first genomic characterization of multidrug-resistant C. auris in Malaysian ICU patients highlights the urgent need for enhanced infection control measures in healthcare settings.

Nosocomial Fungal Infections: Epidemiology, Control Strategies, and Prevention of Candida and Other Yeasts.

The impact of toll-like receptor polymorphisms on susceptibility to fungal infections: a systematic review of genetic and clinical.

Developing prognostic biomarkers for invasive fungal infections.

Invasive candidiasis (IC) remains a significant cause of morbidity and mortality among critically ill, hematologic, and neonatal patients worldwide. Rapid and accurate diagnosis is essential to guide timely antifungal therapy and improve outcomes. Among available diagnostic tools, 1,3-β-D-glucan (BDG), a polysaccharide component of the fungal cell wall, has emerged as a key biomarker. BDG assays allow for early detection of probable IC, often preceding positive blood cultures, and offer prognostic information based on serial measurements. Species-specific differences in Candida cell wall composition influence BDG release and diagnostic sensitivity. Candida albicans generally correlates with high BDG levels, whereas Nakaseomyces glabrata, Candida parapsilosis, and Candida auris exhibit variable or lower glucan exposure, limiting assay sensitivity. BDG performance is affected by patient-specific factors, such as prior surgery, transfusions, or coexisting bacterial infections, which may lead to false-positive results. Molecular techniques, including PCR-based assays, provide complementary diagnostic accuracy and species identification, and their combination with BDG testing enhances sensitivity up to 90%. Serial BDG monitoring supports risk stratification and treatment response assessment, with persistent elevations predicting worse outcomes. In neonatal and pediatric populations, optimal cut-off values remain under investigation, highlighting the need for integration with clinical and microbiological data. Overall, BDG represents a valuable adjunct in a multimodal diagnostic workflow, providing both diagnostic and prognostic insights in invasive candidiasis management.

Candida albicans is a human opportunistic pathogen responsible for superficial and invasive candidiasis. It is one of the emerging nosocomial pathogens infecting immunocompromised and debilitated individuals, increasing the rate of secondary infections in diseases like HIV. The emerging drug resistance among species is making treatment cumbersome. Also, biofilm-forming ability of C. albicans is one of the primary factors contributing to its virulence as its blocks the penetration of drugs, therefore leading to drug inefficacy. Lactiplantibacillus plantarum, a part of the normal flora known for its antimicrobial properties against pathogens. Lactobacillus FL5 was isolated from fermented milk sample and identified as Lactiplantibacillus plantarum. The culture supernatant (CS) of FL5 showed 21mm zone of inhibition against C. albicans MTCC 4748 using agar-well diffusion assay. Lact. plantarum FL5 showed 75.8% co-aggregation with C. albicans at 8h using spectroscopic technique. Both antibiofilm and dispersal potential of CS of FL5 against C. albicans biofilms were evaluated using crystal violet assay and images were recorded using field emission scanning electron microscopy (FESEM). FL5 showed 77% biofilm inhibition and 37% dispersal of preformed C. albicans biofilms. The production of organic acids, phenolics, aldehydes and ketones in CS was estimated using high performance liquid chromatography (HPLC) and fourier transform infrared spectroscopy (FTIR). The gas chromatography- flame ionization detection (GC-FID) showed presence of 0.8 ppm butyric acid, followed by acetic acid (0.143 ppm) and propionic acid (0.115 ppm) in CS. The use of Lact. plantarum as a potential candidate for targeting C. albicans biofilms to tackle antimicrobial resistance and effective treatment.

Invasive candidiasis (IC) remains a major cause of morbidity and mortality worldwide, particularly among critically ill and immunocompromised patients. The emergence of antifungal resistance, especially to azoles, has complicated empirical and targeted therapy. Continuous, region-specific surveillance of Candida species distribution and antifungal susceptibility patterns is therefore essential. We conducted a retrospective observational study of IC cases at Nanjing Drum Tower Hospital, a tertiary care center in eastern China, from January 2010 to December 2023. Candida isolates recovered from sterile body sites were identified to the species level. Antifungal susceptibility testing was performed using standardized commercial platforms, and results were interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Species distribution, temporal trends, ward-specific patterns, and antifungal susceptibility profiles were analyzed. A total of 1,038 non-duplicate Candida isolates were included. Candida albicans was the predominant species (51.1%), followed by C. parapsilosis (15.8%), C. tropicalis (15.5%), and C. glabrata (11.3%). Ascitic fluid (44.5%) and blood (38.2%) were the most common specimen sources, with most isolates originating from the intensive care unit and general surgery wards. Over the 14-year period, the proportions of C. albicans and C. glabrata increased significantly, whereas C. parapsilosis declined. Overall resistance rates to fluconazole and voriconazole were relatively low (3.0% and 2.9%, respectively). However, C. tropicalis exhibited higher azole resistance and non-wild-type phenotypes, particularly to posaconazole. Echinocandin and amphotericin B resistance was rare across major species. In this tertiary-care hospital, C. albicans remained the most frequently isolated Candida species from sterile body sites, whereas C. tropicalis demonstrated the highest azole resistance burden. These findings highlight the importance of sustained local surveillance to inform empirical antifungal strategies.

Candidemia and invasive candidiasis remain significant causes of late-onset sepsis and mortality in very-low-birth-weight infants, especially in low- and middle-income countries. This narrative review synthesizes studies published between 2008 and 2025 in Latin America, addressing epidemiology, species distribution, antifungal susceptibility patterns, risk factors, therapeutic approaches, and clinical outcomes, with international comparisons. Accordingly, we present a qualitative narrative synthesis (see Methods) rather than a formal year-over-year temporal trend quantification. Globally, five species predominate, namely Candida albicans, C. parapsilosis sensu lato (s.I.), Candida tropicalis, Nakaseomyces glabratus, and Pichia kudriavzevii, with a sustained increase in non-albicans species and growing resistance to fluconazole. In Latin America, the burden varies depending on the hospital setting; C. parapsilosis sensu lato (s.I.) predominates in NICUs, and Candidozyma auris has emerged, associated with nosocomial outbreaks and multidrug resistance. Factors such as extreme prematurity, prolonged catheter use, parenteral nutrition, and antibiotics are consistently associated with the risk of infection. Mortality remains high, influenced by diagnostic delays and species characteristics. Standardized microbiological surveillance, accurate identification, and strategies tailored to each clinical setting are required to improve outcomes in this vulnerable population.

Urinary-source candidemia is an uncommon but clinically relevant form of invasive candidiasis, often underrecognized and poorly characterized in the literature. Retrospective single-center study of adult patients with candidemia attributed to a urinary source between 2019 and 2023. Eligible cases were identified using predefined attribution criteria, requiring microbiologically confirmed Candida spp. bloodstream infection with significant candiduria by the same species, in the absence of an alternative clinically plausible source. Among 526 positive blood cultures, 26 fulfilled the predefined criteria for urinary tract source attribution. The median age was 74years. Most patients had a nephro-urological history, with frequent chronic kidney disease (15, 57.7%), obstructive uropathy (19, 73.1%), indwelling urinary devices (21, 80.8%) and recent urological procedures (19, 73.1%). Type 2 diabetes was present in 50% of patients (13), most receiving SGLT2 inhibitors. The majority presented with fever (23, 88.5%), and sepsis was frequent (14, 53.8%). Urinary symptoms were present in only half of the patients (14, 53.8%). Candida albicans was the most frequent isolate (13, 50%); followed by Candida glabrata (8, 30.8%) and Candida parapsilosis (5, 19.2%), both showing high rates of elevated fluconazole MICs. Empirical therapy was often discordant with final susceptibility. Combination antifungal therapy was used in 26.9% (7). Attributable mortality was 23.1% (6 deaths). Independent predictors of mortality included type 2 diabetes, Barthel Index < 50, therapeutic failure and septic shock. Candidemia with a presumed urinary tract source primarily affects frail patients with urological comorbidities, often presents with non-specific symptoms and is associated with significant morbidity and mortality. Combination antifungal therapy may be beneficial in selected cases. Early recognition and individualized management are essential to improve outcomes.

Knowledge and practices of care providers on fungal diseases in the Democratic Republic of the Congo: a cross-sectional study.

Candida fungi are among the most common human fungal pathogens and invasive candidiasis is one of the predominant invasive mycoses that mainly affects hospitalized patients with suppression of the immunological system and breaches in skin or mucosal barriers. Rapid diagnosis and implementation of appropriate antifungal treatment are key to achieving recovery. In recent years, attention has been drawn to the increasing significance of Candida species other than C. albicans, in particular C. auris and fluconazole-resistant C. parapsilosis. The aim of this work was to present the species spectrum and drug susceptibility of 570 Candida strains isolated from candidemia cases diagnosed in patients hospitalized in southern Poland in the period 2017-2022. The results of Candida-positive blood cultures obtained from five hospitals were analyzed. C. albicans was the most common species, accounting for 42.6% of all strains, followed by Nakaseomyces glabratus (formerly C. glabrata) and C. parapsilosis complex-22.1% and 18.8%, respectively. No C. auris was found. Fluconazole resistance was found in 4.9% of C. albicans strains, 34.7% of N. glabratus strains, and 8.7% of C. parapsilosis complex strains.

Candida species are frequently detected in bile cultures during endoscopic retrograde cholangiopancreatography (ERCP), but their clinical significance and the value of antifungal treatment remain unclear. We performed a retrospective single-center cohort study of adults with growth of Candida species from bile cultures collected by ERCP performed between 2010 and 2023. We compared inpatients who received vs. those who did not receive antifungals within one week of ERCP and a subgroup with acute cholangitis. The primary outcome was a composite of death and invasive candidiasis within one year. Secondary outcomes included death, invasive candidiasis, and rehospitalization. Inverse probability of treatment weighting (IPTW) was performed using baseline characteristics. Adjusted hazard ratios and odds ratios were calculated. Among 197 inpatients, 51 (25.9%) received antifungals. At one year, the primary outcome occurred in 23 of 51 patients (45.1%) receiving antifungal therapy and in 67 of 146 patients (45.9%) who did not; the IPTW-adjusted hazard ratio was 0.93 (95% confidence interval 0.69-1.27; p = 0.66). No significant differences were seen in the acute cholangitis subgroup (n = 117). In this study, antifungal therapy was not associated with improved survival, lower rates of invasive candidiasis, or fewer readmissions. Findings support a conservative, stewardship-oriented approach to managing Candida-positive bile cultures in the absence of invasive disease.

Candida glabrata is an opportunistic fungal pathogen that causes both superficial and systemic infections in humans, accounting for 15%-25% of invasive candidiasis cases. Macrophages play a crucial role in antifungal immunity by internalizing C. glabrata; however, the fungus has evolved strategies to survive and even proliferate within phagosomes. It has been suggested that C. glabrata may utilize its life within macrophages to evade immune detection and disseminate throughout the body. We observed that, compared to fungi like C. albicans, C. glabrata only slowly escapes from macrophages, with host cells bursting after 2-3 days. This delay is fungal-driven rather than host-induced and is not solely due to replication in the yeast form per se. We identified protein kinases involved in exit timing, especially the Ksp1 kinase, the deletion of which accelerates macrophage cell lysis. Its loss increases mitophagy and the formation of petites, a respiration-deficient phenotype associated with resistance toward antifungals and, more importantly, to phagocytic killing. Moreover, deletion of KSP1 enhances resistance to multiple antifungals, suggesting that this kinase may be at the core of a broader cross-adaptive survival strategy by C. glabrata. Collectively, our findings indicate that C. glabrata may actively prolong its intramacrophagal phase, which could contribute to immune evasion, antifungal resistance, and potential recurrence of infection. Moreover, these results reinforce the notion of a critical role of petite formation in persistent and recurrent infections. They also show the need to adapt clinical diagnostics and therapy to detect and manage these respiration-deficient variants.IMPORTANCECandida glabrata is a major cause of invasive candidiasis and is difficult to treat due to its intrinsic resistance to antifungal drugs and its ability to survive inside host immune cells. How this pathogen regulates its intracellular lifestyle and exit from macrophages remains poorly understood. We show that C. glabrata actively modulates its interaction with macrophages through the protein kinase Ksp1, which regulates mitochondrial dysfunction and the formation of respiration-deficient cells. These variants display enhanced resistance to two antifungal drugs and killing by phagocytes. Our findings suggest that prolonging the intramacrophage phase and generating stress-resistant variants are key components of C. glabrata's survival strategy. Recognizing these processes has important implications for clinical diagnostics and the management of persistent and recurrent fungal infections.

Candida tropicalis is a leading cause of invasive candidiasis in the Asia-Pacific region with reported crude mortality rates exceeding 50%. The rising prevalence of azole-resistant strains presents a significant clinical challenge. We analyzed 1,016 C. tropicalis clinical isolates collected over nine years from 27 hospitals across North India. Fluconazole resistance was detected in 5.1% (n = 52) of isolates, with cross-resistance observed to voriconazole in 55.7% and itraconazole in 44.2% of isolates. Multilocus sequence typing (MLST) analysis of global 1,630 isolates including 208 Indian and whole-genome sequencing of 716 global isolates (139 Indian) confirmed the clonal emergence and persistence of azole-resistant MLST clade 4 strains in Indian hospitals. Phylogenomic analyses identified that Indian azole-resistant lineage was closely related to azole-resistant isolates from mainland China and Taiwan. The underlying mechanism of resistance involved hotspot mutations (Y132F) in the ERG11 gene along with its duplication, overexpression, and twofold high ergosterol content. Comparative transcriptomics of two clinical isolates exhibiting >512 fold difference in fluconazole susceptibility identified upregulation of virulence-associated genes, ALS7 gene (eightfold), SAP7 and SAP9 (1.6- and 2-fold, respectively) in azole-resistant isolate. Furthermore, azole-resistant isolates showed robust biofilm-associated metabolic activity (twofold), reduced β-glucan exposure, and greater survival in both neutrophil and macrophage killing assays. Notably, azole-resistant lineage exhibits several traits associated with adhesion and immune evasion that could possibly enable its spread in healthcare settings and signals the beginning of a greater spread of this clone. The urgent need for continuous genomic surveillance and antifungal stewardship is warranted to mitigate the spread of multidrug-resistant C. tropicalis.IMPORTANCEInvasive fungal infections affect 6.5 million people annually and are associated with high mortality rates. Despite being the leading cause of invasive yeast infections in the Asia-Pacific, this is the first comprehensive study of Candida tropicalis from India documenting the emergence of azole-resistant clonal lineage (clade 4) in several hospitals in India. Azole resistance is driven by mutations, gene duplication, and overexpression of its target gene ERG11. The Indian azole-resistant isolates showed high genetic relatedness with those from China. Also, resistant isolate showed overexpression of virulence-related genes and robust biofilm formation. Notably, reduced β-glucan exposure in fluconazole-resistant isolates may contribute to their decreased susceptibility to the innate immune system. Importantly, this study provides evidence for the emergence of azole-resistant C. tropicalis lineage in India, which exhibits several traits associated with adhesion and immune evasion that could possibly enable its spread in healthcare settings leading to a public health concern.

The emergence of antimicrobial resistance necessitates the exploration of novel therapeutic agents from natural sources. This study investigated the antimicrobial properties of Clausena anisata fruit ethanol extract (CAFE) and its isolated compounds against 11 bacterial and three fungal strains. The dried fruits were extracted with ethanol using a Soxhlet apparatus. The extract was partitioned and subjected to chromatography to isolate two compounds, which were characterized as stigmasteryl 3-palmitate (C-01) and phellopterin (C-02) using NMR spectroscopy and LC-MS analysis. CAFÉ demonstrated notable inhibition zones in agar well diffusion assays, with the strongest activity against Klebsiella pneumoniae (14.67 ± 2.08 mm) and Staphylococcus saprophyticus (13.67 ± 0.58 mm). Microbroth dilution assays revealed MIC values ranging from 0.0781 to 1.2500 mg/mL for CAFÉ and 0.0781 to 1.2500 mg/mL for stigmasteryl 3-palmitate and phellopterin, respectively. CAFE demonstrated bactericidal activity (MLC/MIC ≤ 4) against Pseudomonas aeruginosa, Proteus mirabilis, Salmonella typhimurium, K. pneumoniae, Streptococcus sanguis, S. saprophyticus, and Candida glabrata, while showing bacteriostatic activity (MLC/MIC > 4) against Candida albicans. Stigmasteryl 3-palmitate exhibited bactericidal activity against P. mirabilis, S. typhimurium, K. pneumoniae, and S. sanguis, with bacteriostatic effects against the other organisms. Phellopterin demonstrated primarily bacteriostatic activity except against S. saprophyticus. Both compounds showed potent fungicidal activity against Candida species. These findings highlight the therapeutic potential of C. anisata fruit and its constituents against typhoid fever, hospital-acquired pneumonia, and invasive candidiasis. This is the first report on the antibacterial and antifungal activities of C. anisata fruit, stigmasteryl 3-palmitate, and phellopterin.