OBJECTIVE: To investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 10⁷ CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- β -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-β-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.
Animals ; Acrolein/pharmacology* ; Candida albicans/physiology* ; Mice, Inbred BALB C ; Candidiasis/pathology* ; Antifungal Agents/therapeutic use* ; Mice ; Fluconazole/therapeutic use* ; Kidney/drug effects* ; Female

OBJECTIVE: To map the potent antifungal properties of the medicinal plant Vitex negundo, in vitro and in silico studies were performed to decipher the pharmacokinetics and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties of their phytoconstituents. METHODS: With the PASS (Prediction of Activity Spectra for Substances) prediction tool, many parameters of V. negundo phenolics were examined, including drug-likeness, bioavailability, antifungal activity, and anti-biofilm activity. Moreover, ADMET parameters were also determined. RESULTS: Eighteen phenolic compounds from V. negundo with significant antifungal activity against Candida species (human fungal pathogens) were detected. The antioxidant activity, inhibition percentage, and minimum inhibitory concentration value of V. negundo phenolic extracts indicate it as an effective antifungal agent for the treatment of candidiasis caused by the fungal pathogen Candida albicans. Many phenolic compounds showed a significantly high efficiency against Candida's planktonic cells and biofilm condition. CONCLUSIONS The phenolics fraction of V. negundo has potent antifungal activities, however, some more pre-clinical studies are a matter of future research to further investigate V. negundo phenolic compound as a potential new antifungal arsenal.
Candida albicans/physiology* ; Vitex/chemistry* ; Antifungal Agents/chemistry* ; Microbial Sensitivity Tests ; Biofilms/drug effects* ; Phenols/pharmacokinetics* ; Plant Extracts/chemistry* ; Antioxidants/pharmacology* ; Phytochemicals/pharmacology* ; Humans

Objective:The objective of this study is to analyze the detection rate, the pathogenic fungus distribution, risk factors and drug sensitivity of fungal infection of external auditory canal in patients diagnosed with chronic otitis media. Methods:The data of a total of 419 patients with chronic suppurative otitis media or middle ear cholesteatoma who were admitted from January 2019 to February 2023 were retrospectively analyzed. Results:A total of 419 patients were included, and 71 patients（16.9%） were positive for fungal culture. The disease mostly occurred in subjects aged 51-60 years old, and patients over 60 years old（47 cases, 66.2%）. From the fungal culture of external auditory canal secretions, 48 cases（11.4%） of Aspergillus and 14 cases（3.3%） of Candida were identified. The prevalence of fungal cultures in patients with chronic suppurative otitis media（20.8%） was significantly higher than that in patients with middle ear cholectestoma（4.9%）. The detection rate of Fungal was significantly increased after topical treatment with antibiotic ear drops（47.0% vs 13.6%）. Most of the isolated fungal strains are wild-type, and they are the sensitivity to voriconazole and fluconazole was the highest（97.2%）. For patients with positive fungal culture, iodoform gauze with triamcinolone acetonide and econazole cream was used to fill the external auditory canal during surgery. There was no significant difference in the tympanic membrane healing rate between patients with positive fungal culture and patients with negative fungal culture at 3 weeks after surgery（98.6% vs 97.7%）. Conclusion:Fungal infections of external auditory canal in patients with chronic otitis media tend to occur in older patients, which is more common in patients with chronic suppurative otitis media. Long-term topical treatment with antibiotic ear drops is an independent risk factor for fungal infection of external auditory canal in patients with chronic otitis media. The isolated fungal strains were highly sensitive to antifungal drugs. Therefore, it is advisable to refrain from employing topical antibiotic treatment for elderly patients with chronic suppurative otitis media/middle ear cholesteatoma, abuse of local antibiotic therapy should be avoided, and Fungal-related pathogenic examinations should be actively performed and anti-fungal drugs should be added if necessary.
Humans ; Middle Aged ; Female ; Male ; Risk Factors ; Retrospective Studies ; Chronic Disease ; Otitis Media, Suppurative/microbiology* ; Ear Canal/microbiology* ; Antifungal Agents/therapeutic use* ; Adult ; Mycoses/epidemiology* ; Aspergillus/isolation & purification* ; Candida/isolation & purification* ; Otitis Media/complications* ; Aged ; Cholesteatoma, Middle Ear/microbiology*

OBJECTIVES: To explore the efficacy of low-intensity pulsed ultrasound (LIPUS) combined with nystatin for treatment of vaginal Candida albicans biofilm infection. METHODS: In vitro cultured Candida albicans biofilm were treated with LIPUS, nystatin, or both, and the minimum inhibitory concentration (MIC) of nystatin was determined. Crystal violet staining, confocal laser microscopy (CLSM) and scanning electron microscopy were used to quantify the biofilm and observe the activity and morphological changes of the biofilms; DCFH-DA was used to detect the changes in reactive oxygen species (ROS). Twenty female New Zealand White rabbits with vaginal inoculation of Candida albicans biofilm were randomized into 4 groups for treatment with normal saline, LIPUS, nystatin, or both LIPUS and nystatin. The changes in vulvar symptoms of the rabbits were observed, and the histopathological and ultrastructural changes of the vagina before and after treatment were observed using HE staining and transmission electron microscopy. RESULTS: In the combined treatment group, the MIC₅₀ and MIC₈₀ of nystatin in Candida albicans biofilms were both reduced by 50% compared with those in nystatin group, and the biofilm clearance rate increased by 26% and 68% compared with nystatin and LIPUS groups, respectively. Compared with nystatin and LIPUS treatment alone, the combined treatment produced stronger effects for inhibiting biofilm activity, causing structural disruption and promoting ROS production. In the rabbit models, the combined treatment more effectively improved vulvar symptoms and inflammatory infiltration, reduced residual vaginal hyphae/strains, and improved ultrastructure of the vaginal epithelium than LIPUS and nystatin treatment alone. CONCLUSIONS LIPUS combined with nystatin produces a significant synergistic antifungal effect against Candida albicans biofilm both in vitro and in vivo.
Animals ; Rabbits ; Female ; Biofilms/drug effects* ; Candida albicans/physiology* ; Nystatin/therapeutic use* ; Candidiasis, Vulvovaginal/microbiology* ; Ultrasonic Waves ; Antifungal Agents/therapeutic use* ; Vagina/microbiology* ; Ultrasonic Therapy ; Microbial Sensitivity Tests ; Combined Modality Therapy

OBJECTIVE: To analyze the pathogens distribution in patients with ventilator-associated pneumonia (VAP), and their association with anti-β-glucan receptor-1 (Dectin-1)/spleen tyrosine kinase (Syk) signaling pathway, and to provide scientific basis for formulating more effective treatment strategies and preventive measures. METHODS: A prospective study was conducted. 160 patients with VAP admitted to the department of critical care medicine of Xingtai People's Hospital from January 2021 to March 2023 were enrolled. The respiratory secretions of patients were collected for Candida colonization analysis, and then the bacteria in the respiratory secretions were identified by automatic microbial identification instrument. The expression levels of Dectin-1 and Syk in peripheral blood mononuclear cells were detected by fluorescent immunopolymerase chain reaction. Clinical pulmonary infection score (CPIS) was performed based on imaging, clinical and microbiological criteria. The basic data, pathogen distribution, Dectin-1 and Syk expression levels and CPIS score of the two groups were compared. Spearman test was used to analyze the correlation between the expression levels of Dectin-1 and Syk and respiratory Candida colonization and CPIS score. RESULTS: 160 VAP patients, 97 were Candida colonized (colonized group) and 63 were not (non-colonized group). There were significantly differences in gender (males: 57.73% vs. 41.27%, P = 0.042) and age (years: 57.98±12.46 vs. 62.09±10.61, P = 0.029) between the colonized group and the non-colonized group, while there were no significantly differences in the data of duration of mechanical ventilation, underlying diseases and primary diseases. The distribution of pathogenic bacteria showed that the infection rate of Staphylococcus aureus in the colonized group was significantly higher than that in the non-colonized group (24.74% vs. 7.94%, P < 0.05), and there was no significantly difference in the infection rate of other G-positive and G-negative bacteria between the two groups. The CPIS score in the colonized group was significantly higher than that in the non-colonized group (8.73±0.43 vs. 7.31±0.39, P < 0.01), and the expression levels of Dectin-1 and Syk in peripheral blood mononuclear cells were significantly higher than those in the non-colonized group (Dectin-1/U6: 0.86±0.22 vs. 0.47±0.16, Syk/U6: 0.77±0.18 vs. 0.42±0.11, both P < 0.01). The expression levels of Dectin-1 and Syk in peripheral blood mononuclear cells of VAP patients were significantly positively correlated with the colonization of respiratory Candida (r values were 0.754 and 0.631, respectively, both P < 0.05), and were significantly positively correlated with CPIS score (r values were 0.594 and 0.618, respectively, both P < 0.05). CONCLUSION The proportion of Staphylococcus aureus in VAP patients with respiratory Candida colonization is higher, and Dectin-1/Syk signaling pathway is significantly positively correlated with respiratory Candida colonization and CPIS score.
Humans ; Syk Kinase ; Lectins, C-Type/metabolism* ; Signal Transduction ; Pneumonia, Ventilator-Associated/metabolism* ; Prospective Studies ; Male ; Female ; Middle Aged ; Candida ; Aged

In this study, we employed a combination of genome mining and heteronuclear single quantum coherence (HSQC)-based small molecule accurate recognition technology (SMART) technology to search for fernane-type triterpenoids. Initially, potential endophytic fungi were identified through genome mining. Subsequently, fine fractions containing various fernane-type triterpenoids were selected using HSQC data collection and SMART prediction. These triterpenoids were then obtained through targeted isolation and identification. Finally, their antifungal activity was evaluated. As a result, three fernane-type triterpenoids, including two novel compounds, along with two new sesquiterpenes and four known compounds were isolated from one potential strain, Diaporthe discoidispora. Their structures were elucidated through analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR) spectroscopic data. The absolute configurations were determined using single-crystal X-ray diffraction analysis and electron capture detector (ECD) analysis. Compound 3 exhibited moderate antifungal activity against Candida albicans CMCC 98001 and Aspergillus niger.
Triterpenes/isolation & purification* ; Antifungal Agents/isolation & purification* ; Molecular Structure ; Candida albicans/drug effects* ; Ascomycota/genetics* ; Magnetic Resonance Spectroscopy ; Aspergillus niger/drug effects* ; Genome, Fungal ; Microbial Sensitivity Tests

BACKGROUND

Invasive candidiasis is defined by the growth of Candida species in the bloodstream or other internal organs. It is a global concern due to increasing multidrug resistance and high mortality rates. This study aimed to update prevalence data on Candida infections in the Philippines, analyzing demographic factors (age, sex), specimen sources, and associated risk factors. We compared antifungal resistance patterns against CLSI epidemiological cutoff values (ECVs) and clinical breakpoints and examined MIC variations by underlying disease to inform potential standardized empiric therapies.

We conducted a retrospective analytical cross-sectional study (SLMC-IERC approval, minimal risk) reviewing one year of Candida speciation and susceptibility results from January 2024 to December 2024 at a private tertiary hospital. All aseptically collected samples that tested positive for Candida species were included. Respiratory and wound specimens required a Gram stain demonstrating yeasts and hyphae prior to culture, while urine cultures were included only if they yielded ≥100,000 CFU/mL. Identification and susceptibility testing were performed using the VITEK 2 system, with results interpreted using CLSI breakpoints and ECVs.

Among 266 patients with Candida infections, invasive candidiasis predominated in those aged ≥60 years (66.4%). Candida albicans (21.7%) and Candida tropicalis (13.5%) were more frequent in females, while Candida parapsilosis (13.2%) and Candida glabrata (5.3%) were more common in males. Blood and CSF samples strongly correlated with invasive disease and underlying risk factors. C. albicans was linked to infection-related conditions (13.9%), malignancy (9.0%), and cardiovascular disease (6.8%). C. parapsilosis(23.3%) and C. tropicalis (20.7%) were frequently associated with infection, malignancy, and metabolic disorders. C. glabrata (7.5%), noted for antifungal resistance, was isolated in patients with direct infections (3.4%) and malignancies (1.9%). Among azoles, fluconazole demonstrated greater susceptibility against Candida species, requiring lower concentrations for inhibition, despite a higher resistance rate (13.22%) compared to voriconazole (8.95%). Among echinocandins, micafungin showed better susceptibility than caspofungin. Amphotericin B demonstrated the highest overall susceptibilit y (93 –10 0%), though MICs approached ECV limits. Most susceptible MIC values were fluconazole 0.5 μg/mL for C. albicans and C. parapsilosis, 1.0 μg/mL for C. tropicalis; voriconazole and caspofungin 0.12 μg/mL; micafungin 0.06 μg/mL; amphotericin B 0.5 μg/mL; and flucytosine

These findings support a species-specific, risk-adapted approach to antifungal therapy, incorporating demographic and clinical variables. Continuous surveillance of invasive candidiasis prevalence and antifungal MIC trends, with periodic breakpoint updates, is crucial to preserve therapeutic efficacy. Effective management of multidrug-resistant Candidainfections also requires close collaboration between clinicians and pharmacists, as well as the development of new dosing strategies based on pharmacokinetic/pharmacodynamic (PK/PD) principles.

Objective: To explore the relationship between extracellular enzymes activity and virulence of Candida glabrata clinical isolates based on the infection model of Galleria mellonella larvae. Methods: Using experimental research methods, 71 strains of non-repetitive Candida glabrata were collected from Qinghai Provincial People's Hospital from June 2021 to January 2022. Bovine serum protein agar medium, egg yolk agar medium, sheep blood agar medium, Tween-80 agar medium and triglyceride agar medium were used to detect the aspartyl protease activity, phospholipase activity, hemolysis activity, esterase activity and lipase activity of Candida glabrata. Median lethal concentration (LC₅₀) was calculated by using 1.25×10⁸ CFU/ml,2.50×10⁸ CFU/ml,3.75×10⁸ CFU/ml,5.00×10⁸ CFU/ml suspension of Candida glabrata ATCC2001 to infect Galleria mellonella larvae. Histopathological and etiological analysis was performed to determine whether the infection model was successfully established. The clinical isolates of Candida glabrata were configured to infect Galleria mellonella larvae with LC₅₀ concentration to detect the pathogenicity of Galleria mellonella larvae.Spearman test or Pearson test were used to analyze the correlation between the extracellular enzyme activity of Candida glabrata clinical isolates and the pathogenicity of Galleria mellonella larvae. Results: 71 strains of Candida glabrata isolated clinically were detected to have low hemolytic activity after 2 days of culture. Aspartyl protease was detected after 4 days of culture, among which 7 strains (9.86%), 19 strains (26.76%) and 45 strains (63.38%) showed low, medium and high aspartyl protease activity. After 7 days of culture, 71 strains did not detect phospholipase, esterase and lipase activities. Candida glabrata on Galleria mellonella larvae of LC₅₀=2.5×10⁸ CFU/ml Fungal spore were found in the intestinal tissue pathological section of Galleria mellonella larvae in the experimental group, and Candida glabrata was identified by the microbial Mass Spectrometry after culture, while no fungi were found in the pathological section and culture of the control group. Spearman test shows that, there was a linear positive correlation between aspartyl protease activity and the survival rate of Galleria mellonella larvae (r = 0.73, P<0.01), the difference was statistically significant.Pearson test shows that, there was no significant linear relationship between hemolytic activity and survival rate of Galleria mellonella larvae (r = 0.16, P = 0.34), the difference was not statistically significant. Conclusion: The clinical isolates of Candida glabrata in this study had aspartyl protease activity and low hemolytic activity, but no phospholipase, esterase and lipase activity. The activity of aspartyl aspartyl protease of Candida glabrata was positively correlated with the pathogenicity of Galleria mellonella larvae.
Animals ; Sheep ; Larva/microbiology* ; Virulence ; Candida glabrata ; Agar ; Moths/microbiology* ; Esterases ; Aspartic Acid Proteases ; Lipase

Background: Thalassemia is a common inherited hemolytic disorder characterized by the absence or reduction of one of the globin chains. Beta thalassemia major generally has oral cavity manifestations. Patients with beta thalassemia major often require routine blood transfusion. However, this treatment has the side effect of accumulating iron in the salivary glands, which increase the risk of dental caries, gingivitis, and secondary infection from Candida albicans. Objective: The aim of this review is to explain the relationship of salivary iron levels and the effects of iron accumulation on dental caries, gingivitis, and Candida albicans infection. Methods: A comprehensive search was performed on PubMed, Scopus, and Google Scholar databases using the keywords beta thalassemia major, iron, dental caries, gingivitis, Candida albicans. Results: Iron is an essential micronutrient needed by Candida albicans for its growth and virulence. Blood transfusion in patients with beta thalassemia major can lead to a buildup of iron in the salivary glands and trigger the formation of non-transferrin bound iron (NTBI). NTBI can circulate in plasma and form a reactive oxygen species (ROS) that stimulate the formation of biofilms and increase dental caries. ROS may affect several genes associated with the inflammatory process and increase the incidence of gingivitis. It can also reduce salivary secretion in patients with thalassemia-β major that cause dysbiosis, which triggers an overgrowth of Candida albicans. Conclusion The excess iron in patients with beta thalassemia major increase the risk of dental caries, gingivitis, and Candida albicans infection.
beta thalassemia major ; iron ; dental caries ; gingivitis ; Candida albicans

Objective: To establish a nested recombinant enzyme-assisted polymerase chain reaction (RAP) technique combined with recombined mannose-binding lectin protein (M1 protein)-magnetic beads enrichment for the detection of Candida albicans (C. albicans) and Candida tropicalis (C. tropicalis) in blood samples for the early diagnosis of candidemia albicans and candidiemia tropicalis. Methods: The primer probes for highly conserved regions of the internal transcribed spacerregions of C. albicans and C. tropicalis were deigned to establish RAP assays for the detections of C. albicans and C. tropicalis; The sensitivity and reproducibility of nucleic acid tests with gradient dilutions of standard strains and specificity of nucleic acid tests with common clinical pathogens causing bloodstream infection were condcuted. M1 protein-magnetic bead enriched plasma C. albicans and C. tropicalis were used for RAP and PCR in with simulated samples and the results were compared. Results: The sensitivity of the established dual RAP assay was 2.4-2.8 copies/reaction, with higher reproducibility and specificity. M1 protein-magnetic bead enrichment of pathogen combined with the dual RAP assay could complete the detections of C. albicans and C. tropicalis in plasma within 4 hours. Fie the pathogen samples at concentration <10 CFU/ml, the number of the samples tested by RAP was higher than that tested by PCR after enrichment. Conclusion: In this study, a dual RAP assay for the detections of C. albicans and C. tropicalis in blood sample was developed, which has the advantages of accuracy, rapidity, and less contaminants and has great potential for rapid detection of Candidemia.
Humans ; Lectins ; Candida ; Candidemia ; Reproducibility of Results ; Polymerase Chain Reaction ; Nucleic Acids ; Magnetic Phenomena