OBJECTIVE: To evaluate the efficacy of cis-2-dodecenoic acid (BDSF) in the treatment and prevention of vaginal candidiasis in vivo. METHODS: The activities of different concentrations of BDSF against the virulence factors of Candida albicans (C. albicans) were determined in vitro. An experimental mouse model of Candida vaginitis was treated with 250 μmol/L BDSF. Treatment efficiency was evaluated in accordance with vaginal fungal burden and inflammation symptoms. RESULTS: In vitro experiments indicated that BDSF attenuated the adhesion and damage of C. albicans to epithelial cells by decreasing phospholipase secretion and blocking filament formation. Treatment with 30 μmol/L BDSF reduced the adhesion and damage of C. albicans to epithelial cells by 36.9% and 42.3%, respectively. Treatment with 200 μmol/L BDSF completely inhibited phospholipase activity. In vivo mouse experiments demonstrated that BDSF could effectively eliminate vaginal infection and relieve inflammatory symptoms. Four days of treatment with 250 μmol/L BDSF reduced vaginal fungal loads by 6-fold and depressed inflammation. Moreover, BDSF treatment decreased the expression levels of the inflammatory chemokine-associated genes MCP-1 and IGFBP3 by 2.5- and 2-fold, respectively. CONCLUSION BDSF is a novel alternative drug that can efficiently control vaginal candidiasis by inhibiting the virulence factors of C. albicans.
Animals ; Candida albicans ; drug effects ; metabolism ; pathogenicity ; physiology ; Candidiasis, Vulvovaginal ; drug therapy ; genetics ; immunology ; microbiology ; Chemokine CCL2 ; genetics ; immunology ; Disease Models, Animal ; Fatty Acids, Monounsaturated ; administration & dosage ; Female ; Fungal Proteins ; genetics ; metabolism ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; genetics ; immunology ; Mice ; Virulence ; drug effects ; Virulence Factors ; genetics ; metabolism

The hyphal development of Candida albicans (C. albicans) has been considered as an essential virulent factor for host cell damage. However, the missing link between hyphae and virulence of C. albicans is also been discovered. Here, we identified that the null mutants of ERG3 and ERG11, two key genes in ergosterol biosynthesis pathway, can form typical hyphae but failed to cause the oral mucosal infection in vitro and in vivo for the first time. In particular, the erg3Δ/Δ and erg11Δ/Δ strains co-cultured with epithelial cells significantly reduced the adhesion, damage, and cytokine (interleukin-1α (IL-1α)) production, whereas the invasion was not affected in vitro. Importantly, they were incapable of extensive hyphal invasion, formation of micro-abscesses, and tongue epithelium damage compared to wild type due to the decrease of the colonization and epithelial infection area in a murine oropharyngeal candidiasis model. The fluconazole (FLC), an antifungal targeted at ergosterol biosynthesis, relieved the epithelial infection of C. albicansin vitro and in vivo even under non-growth inhibitory dosage confirming the virulent contribution of ergosterol biosynthesis pathway. The erg3Δ/Δ and erg11Δ/Δ strains were cleared by macrophages similar to wild type, whereas their virulence factors including agglutinin-like sequence 1 (Als1), secreted aspartyl proteinase 6 (Sap6), and hyphal wall protein-1 (Hwp1) were significantly reduced indicated that the non-toxicity might not result from the change on immune tolerance but the defective virulence. The incapacity of erg3Δ/Δ and erg11Δ/Δ in epithelial infection highlights the contribution of ergosterol biosynthesis pathway to C. albicans pathogenesis and fluconazole can not only eliminate the fungal pathogens but also reduced their virulence even at low dosage.
Animals ; Antifungal Agents ; pharmacology ; Candida albicans ; drug effects ; genetics ; pathogenicity ; Candidiasis, Oral ; drug therapy ; genetics ; microbiology ; Fluconazole ; pharmacology ; Genes, Fungal ; genetics ; Mice ; Microscopy, Electron, Scanning ; Potassium Channels ; genetics ; Virulence

OBJECTIVETo investigate the clinical features of invasive candidiasis in children and the risk factors for Candida bloodstream infection.

METHODSA retrospective study was performed on 134 children with invasive candidiasis and hospitalized in 5 tertiary hospitals in Urumqi, China, between January 2010 and December 2015. The Candida species distribution was investigated. The clinical data were compared between the patients with and without Candida bloodstream infection. The risk factors for Candida bloodstream infection were investigated using multivariate logistic regression analysis.

RESULTSA total of 134 Candida strains were isolated from 134 children with invasive candidiasis, and non-albicans Candida (NAC) accounted for 53.0%. The incidence of invasive candidiasis in the PICU and other pediatric wards were 41.8% and 48.5% respectively. Sixty-eight patients (50.7%) had Candida bloodstream infection, and 45 patients (33.6%) had Candida urinary tract infection. There were significant differences in age, rate of use of broad-spectrum antibiotics, and incidence rates of chronic renal insufficiency, heart failure, urinary catheterization, and NAC infection between the patients with and without Candida bloodstream infection (P<0.05). The multivariate logistic regression analysis showed that younger age (1-24 months) (OR=6.027) and NAC infection (OR=1.020) were the independent risk factors for Candida bloodstream infection.

CONCLUSIONSThe incidence of invasive candidiasis is similar between the PICU and other pediatric wards. NAC is the most common species of invasive candidiasis. Candida bloodstream infection is the most common invasive infection. Younger age (1-24 months) and NAC infection are the risk factors for Candida bloodstream infection.

Adolescent ; Age Factors ; Candidiasis ; drug therapy ; microbiology ; Child ; Child, Preschool ; Female ; Fungemia ; etiology ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Male ; Retrospective Studies ; Risk Factors

INTRODUCTIONTreatment of acute lymphoblastic leukaemia (ALL) using intensive chemotherapy has resulted in high cure rates but also substantial morbidity. Infective complications represent a significant proportion of treatment-related toxicity. The objective of this study was to describe the microbiological aetiology and clinical outcome of episodes of chemotherapy-induced febrile neutropaenia in a cohort of children treated for ALL at our institution.

MATERIALS AND METHODSPatients with ALL were treated with either the HKSGALL93 or the Malaysia-Singapore (Ma-Spore) 2003 chemotherapy protocols. The records of 197 patients who completed the intensive phase of treatment, defined as the period of treatment from induction, central nervous system (CNS)-directed therapy to reinduction from June 2000 to January 2010 were retrospectively reviewed.

RESULTSThere were a total of 587 episodes of febrile neutropaenia in 197 patients, translating to an overall rate of 2.98 episodes per patient. A causative pathogen was isolated in 22.7% of episodes. An equal proportion of Gram-positive bacteria (36.4%) and Gram-negative bacteria (36.4%) were most frequently isolated followed by viral pathogens (17.4%), fungal pathogens (8.4%) and other bacteria (1.2%). Fungal organisms accounted for a higher proportion of clinically severe episodes of febrile neutropaenia requiring admission to the high-dependency or intensive care unit (23.1%). The overall mortality rate from all episodes was 1.5%.

CONCLUSIONFebrile neutropaenia continues to be of concern in ALL patients undergoing intensive chemotherapy. The majority of episodes will not have an identifiable causative organism. Gram-positive bacteria and Gram-negative bacteria were the most common causative pathogens identified. With appropriate antimicrobial therapy and supportive management, the overall risk of mortality from febrile neutropaenia is extremely low.

Candidiasis ; epidemiology ; Chemotherapy-Induced Febrile Neutropenia ; epidemiology ; microbiology ; Child ; Cohort Studies ; Escherichia coli Infections ; epidemiology ; Gram-Negative Bacterial Infections ; epidemiology ; Gram-Positive Bacterial Infections ; epidemiology ; Humans ; Influenza, Human ; epidemiology ; Klebsiella Infections ; epidemiology ; Mycoses ; epidemiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Pseudomonas Infections ; epidemiology ; Retrospective Studies ; Singapore ; epidemiology ; Staphylococcal Infections ; epidemiology ; Virus Diseases ; epidemiology

OBJECTIVETo investigate the effects of butyl alcohol extract of Baitouweng decoction ( BAEB) on yeast-to-hyphae transition of Candida albicans isolates from vulvovaginal candidiasis (VVC) in alkaline pH.

METHODSerial 2-fold dilution assay was used to determine the minimal inhibitory concentrations (MICs) of Baitouweng decoction extracts against C. albicans isolates from VVC, XTT assay was applied to determine the metabolic activity of C. albicans hypha treated by BAEB for 6 h. The morphological change of C. albicans treated by BAEB was inspected at different pH by inverted microscope, fluorescence microscope, scanning electron microscopy (SEM). Solid agar plate and semi-solid agar were utilized to evaluate colony morphology and invasive growth of C. albicans, respectively. Quantitative Real-time PCR (qRT-PCR) was adopted to observe the expressions of hyphae-specific genes including HWP1, ALS3, CSH1, SUN41 and CaPDE2.

RESULTThe MIC of BAEB against C. albicans is less than that of other extracts; hyphae grow best at pH 8. 0; 512 mg · L(-1) and 1,024 mg · L(-1) BAEB could inhibit formation of hyphae and influence colony morphology. When treated by 512 mg · L(-1) and 1,024 mg · L(-1) BAEB, the colonies became smooth; while by 0 and 256 mg · L(-1) BAEB, the colonies became wrinkled. In semi-solid agar, the length of hyphae decreased steadily as the concentration of BAEB lowered. The expression of HWP1, ALS3, CSHl, SUN41 were downregulated by 5.12, 4.26, 3.2 and 2.74 folds, and CaPDE2 was upregulated by 2.38 fold.

CONCLUSIONBAEB could inhibit yeast-to-hyphae transition of C. albicans isolates from VVC in alkaline pH.

Antifungal Agents ; isolation & purification ; pharmacology ; Candida albicans ; drug effects ; genetics ; growth & development ; Candidiasis, Vulvovaginal ; drug therapy ; microbiology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Humans ; Hydrogen-Ion Concentration ; Hyphae ; drug effects ; growth & development

No abstract available.
Adult ; Aged ; Antifungal Agents/therapeutic use ; Candida/*genetics/isolation & purification ; Candidiasis/diagnosis/drug therapy/*microbiology ; *Diagnostic Errors ; Female ; Fluconazole/therapeutic use ; Humans ; Infant ; Lymphoma, T-Cell/diagnosis/microbiology ; Male ; Reagent Kits, Diagnostic/*standards

OBJECTIVETo observe the inhibitory effect of different extract fractions from Longdan Xiegan decoction on biofilms of Candida albicans, and discuss its possible mechanism.

METHODThe micro-dilution method and the XTT reduction assay were adopted to explore the antifungal activity of different extract fractions from Longdan Xiegan decoction and detect the inhibitory effect of different extracts on biofilms of C. albicans. The expression quantity of the adhesion related gene ALS1 and hypha formation SUN41 were detected by qRT-PCR.

RESULTThe MICs of extracts from Longdan Xiegan decoction, including petroleum ether, water, butanol, methanol and ethyl acetate, against C. albicans were > 1 000, > 1 000, > 1 000, 125, 125 mg x L(-1). The SMIC50 against biofilms of C. albicanswere > 1 000, > 1000, > 1 000, 500, 500 mg x L(-1). The SMIC50 were > 1 000, > 1 000, > 1 000, > 1 000 and 1 000 mg x L(-1). 1 000 mg x L(-1) ethyl acetate extracts could considerably inhibit the expression of the adhesion related gene ALS1 and hypha formation SUN41.

CONCLUSIONThe ethyl acetate extract showed the greatest activity against Candida albicans biofilms.

Antifungal Agents ; pharmacology ; Biofilms ; drug effects ; growth & development ; Candida albicans ; drug effects ; growth & development ; Candidiasis ; drug therapy ; microbiology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Hyphae ; drug effects ; growth & development ; Microbial Sensitivity Tests

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)
14-alpha Demethylase Inhibitors/adverse effects/therapeutic use ; Adolescent ; Adult ; Aged ; Antifungal Agents/adverse effects/*therapeutic use ; Aspergillosis/complications/*drug therapy ; Candidiasis/complications/*drug therapy ; Coccidioidomycosis/complications/drug therapy ; Febrile Neutropenia/complications/drug therapy ; Female ; Hematologic Neoplasms/complications/drug therapy/*microbiology ; Humans ; Itraconazole/adverse effects/*therapeutic use ; Male ; Mannans/blood ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Young Adult

Patients who suffer severe burns are at increased risk for local and systemic infections. The incidence of fungal infections has increased in recent years, and these infections represent a major issue in burn intensive care units. Herein, we report three cases of fungal infection due to Candida species occurring in patients undergoing supportive therapy and antibiotic treatment during their hospitalization. Two of these patients were infected with Candida parapsilosis, and one was infected with Candida albicans. The risk factors for these patients' Candida infections were multiple and prolonged courses of antimicrobial treatment, steroid treatment, tracheal intubation and smoke inhalation. Susceptibility testing of nine antifungal compounds was performed, and the minimum inhibitory concentration (MIC) values of all isolated strains were lower than the breakpoint MIC value for resistance of the relevant drug. All three patients were cured by treatment with antifungal agents. Candida infection may occur 1 - 3 weeks after thermal injury, and the prompt recognition and treatment of such infections with antifungal therapies may result in decreased morbidity and mortality associated with these infections in burn patients.
Adult ; Antifungal Agents ; therapeutic use ; Burns ; complications ; microbiology ; Candida albicans ; drug effects ; pathogenicity ; Candidiasis ; drug therapy ; etiology ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged

Reports of combined candidal and herpetic esophagitis in immunocompetent states are rare and sporadic. A 44-year-old previously healthy lady presented with a one week history of progressive dysphagia, odynophagia and fever. Esophagogastroduodenoscopy (EGD) showed extensive desquamation of the entire esophagus except for distal 4 cm. Histopathological examination revealed ulcerated and inflamed squamous epithelium with the margin of ulcer showing a few overhanging squamous cells with dense eosinophilic cytoplasm, multinucleated and faceted nuclei with glassy chromatin, and an occasional Cowdry type A intranuclear inclusion bodies. Few candidal spores were seen in the underlying stroma. Intravenous acyclovir, fluconazole and pantoprazole were initiated. Oral analgesics were given for pain relief. She was treated for a total of 14 days. She showed significant improvement and was tolerating oral intake after discharge. The patient was asymptomatic with no evidence of recurrence at a 2-month follow-up.
Adult ; Antifungal Agents ; therapeutic use ; Antiviral Agents ; therapeutic use ; Candidiasis ; diagnosis ; drug therapy ; microbiology ; Esophagitis ; diagnosis ; drug therapy ; microbiology ; virology ; Esophagus ; microbiology ; pathology ; virology ; Female ; Herpes Simplex ; diagnosis ; drug therapy ; virology ; Humans ; Inclusion Bodies, Viral ; Spores, Fungal ; Treatment Outcome