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[Candida urinary tract infection with special reference to ascending pyelonephritis].

The pathogenesis of Candida urinary tract infection (UTI) has been investigated clinically and experimentally with special reference to ascending pyelonephritis in rats. Among the Candida species, Candida albicans was most frequently isolated from clinical specimens including urine in two medical centers, one in Japan and the other in the United States. The isolates of C. albicans serotype B showed a significantly lower susceptibility to 5-fluorocytosine compared to those of serotype A (p less than 0.01). The distribution pattern of the serum antibody titers against C. albicans in 20 candiduria patients (C. albicans 19 and Candida tropicalis 1) was similar to that in 23 bacterial complicated UTI patients. All patients with candiduria had underlying diseases of the urinary tract, such as neurogenic bladder, bladder cancer or benign prostatic hyperplasia: indwelling urinary catheters were present in 15 patients and all had received antimicrobial agents before the study. Ascending Candida pyelonephritis has been investigated in female rats which were transurethrally inoculated into the bladder with C. albicans ATCC 10259 strain. The incidence of Candida pyelonephritis was approximately 80% in rats treated with cyclophosphamide and more than 70% in rats with partial ureteral obstruction. There was a significant relationship between renal and urinary Candida cell populations (p less than 0.01). Furthermore, a significant relationship was revealed between renal Candida cell populations and histological grades of pyelonephritis (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Antibody base titer against the yeast fungus of the Candida family in childhood].

Because of the omnipresence of yeasts belonging to the species Candida it is not easy to distinguish between contamination and infection in patients (e.g. swabs from skin or mucous membranes). Antibody detection may be helpful for the diagnosis of severe Candida infection. However, during early infancy most children produce Candida antibodies without the signs of infection. Those basic antibody titers have to be considered when antibody determination becomes necessary to prove acute systemic Candida infection. Lowest titers against Candida were detected in the first year of life based on the decrease of the maternally transmitted antibodies. However, Candida colonization rates are most frequently detectable in this period. At the age of 10 years the antibody titers of adults are reached. The determination of one single titer does not justify any conclusion of Candida infection because the antibody basic titers are widely scattered. Systemic Candida infections still remain a more or less clinical diagnosis which can only be confirmed by the antibody titer dynamics.

Antibodies, Fungal↗

Candida colonization of the oral cavity.

A quantitative study of candida colonization of the oral cavity was made in 20 normal persons, 20 patients receiving regular dialysis treatment, 21 patients who underwent operation and were in a general surgical ward and in 20 critically ill patients who had undergone operation and were in an intensive therapy unit. Candida colonization was common in the patients who had operations, and levels were highest in those receiving antibiotics. However, the administration of antibiotics was not the only factor accounting for high candida colonization, since many of the patients studied, receiving regular dialysis treatment and antibiotic therapy, had only low levels of colonization. Candida levels in the oral cavity were highest in the critically ill patients, two of whom had candida infection of the oral cavity and one patient who had systemic candidiasis. Within this group, candida colonization was not significantly different, according to the clinical outcome or the response to recall antigens. This increased candida colonization of the oral cavity may be important in the development of candida infection in these patients.

Adolescent↗

The cellular immunity in patients sensitized to Candida albicans and its corresponding humoral response.

Ten non-sensitized normal blood donors and thirty five patients with a strongly positive intracutaneous test to Candida albicans, positive anamnesis to Candida allergy, or with an actual Candida infection demonstrated by positive cultures of the focus, were studied. In all of them, an evaluation of the humoral and cellular response to Candida antigens, was performed both in vivo and in vitro. The results obtained in the tests performed in the control group were considered as extreme values of a normal response and taken as reference in order to evaluate the patients' response. The results of the test performed on the 35 patients were processed in an IBM S.370/M.125 computer and submitted to a General Taxonomy Program in order to group the patients according to their characteristics and similar behaviour. Two main groups, each one including three minor groups, were obtained and only one individual was not classified. According to this classification it was possible to distinguish two immunological patterns: a) The patients that had a normal or increased percentage of T lymphocytes were capable of responding adequately to Candida albicans antigens. They showed positive immediate and delayed skin tests, increased hemagglutination titres, increased lgE values, and their lymphocytes were capable of undergoing positive blast transformation. Those patients from this group who had a candidaemia at the time of the study, reached the highest hemagglutination values and presented precipitin antibodies as a characteristic. b) The patients that had a decreased percentage of T lymphocytes presented a partial deficiency in their response to Candida albicans antigens. They showed negative delayed skin tests; hemagglutination and precipitation tests both negative, normal lgE values and their lymphocytes did not undergo blast transformation. These findings suggest that a normal percentage of T cells is required in order to obtain a suitable cellular response against Candida albicans, and that an appropriate co-operation between T and B cells is also necessary in order to obtain a good humoral response to Candida antigens.

Antibody Formation↗

Characterization of two monoclonal antibodies against secretory proteinase of Candida tropicalis DSM 4238.

Two murine IgM monoclonal antibodies (mAb; MT1 and MT2), which were produced against the secretory aspartic proteinase of Candida tropicalis DSM 4238, are described. Both antibodies reacted with the native and denatured conformations of the homologous proteinase antigen but showed different patterns of reactivity with other related proteinases (Candida albicans CBS 2730, serotype A; C. albicans ATCC 48867, serotype B; Candida parapsilosis DSM 4237) and with porcine pepsin. Neither of the antibodies inhibited the proteolytic activity of the homologous enzyme. MT1 also reacted with mannoproteins of C. tropicalis DSM 4238 and C. albicans CBS 2730 and immunofluorescence revealed that this antibody bound to the surface of blastoconidia and pseudomycelia of these two Candida species. A reaction with blastoconidia only was observed with C. albicans serotype B. MT1 also reacted weakly with Candida guilliermondii, but not with C. parapsilosis, Candida glabrata, Candida krusei or Candida kefyr. MT2 did not bind to fungal surfaces. Preliminary experiments suggested that mAb MT1 may recognize a carbohydrate epitope, while MT2 binds to an epitope consisting of the protein part of the enzyme. The two antibodies were used in an ELISA for the detection of proteinase antigen. ELISA with MT1 or MT2 as coating antibodies and a specific protein epitope recognizing mAb-biotin conjugate was able to detect 4 ng ml-1 of antigen. Trials with 26 sera from fungemic patients and 14 sera from controls suggest that MT2 is of potential value in antigen-directed serodiagnosis.

Animals↗

[Measurement of Candida-specific lymphocyte proliferation by flow cytometry in children with atopic dermatitis].

To study a role of Candida albicans in the development of atopic dermatitis (AD) from the viewpoint of cellular responses, we measured Candida-specific lymphocyte proliferation by flow cytometry in children with AD. There was no apparent age-dependent change in the level of Candida-SIF (stimulation index measured by flow cytometry) in either AD or non-atopic control subjects. The level of Candida-SIF was significantly higher in AD patients than in non-atopic controls (178.0 +/- 89.3 vs 137.9 +/- 37.6, p < 0.02), and the incidence of subjects with the elevated Candida-SIF level (> or = 200) was significantly higher in AD patients than in non-atopic controls (27.9% (17/61) vs 2.6% (1/38), p < 0.005). There was no correlation between the levels of Candida-SIF and Candida-specific IgE antibody. These results suggest that Candida albicans contributes to the development of AD in some patients not only by Type I, but also by Type IV hypersensitivity reactions.

Adolescent↗

A comparison of three methods for detecting Candida albicans in patients with Sjögren's syndrome.

OBJECTIVE: An immediate chairside technique (Latex Candida) for the detection of Candida albicans was compared with a simple tube culturing technique (Oricult) and the traditional laboratory culturing technique in patients with Sjögren's syndrome. METHOD AND MATERIALS: Subjects with primary (n = 9) and secondary (n = 9) Sjögren's syndrome (mean age of 56.7 years; all female) and an age- and sex-matched group of control subjects (n = 9) were selected. Three different methods for culturing Candida albicans were performed for each subject. One culturette was plated on a trypticase soy-agar streptomycin-vancomycin medium plate and incubated for 48 hours at 37 degrees C. Another swab was plated on a reagent paper with the Latex Candida test kit. The third swab was placed in a culture media tube using the Oricult kit and incubated for 48 hours at 37 degrees C. RESULTS: All three techniques indicated a significant difference in the prevalence of Candida between the control group and both Sjögren's groups. The Latex Candida technique indicated that 78% of all Sjögren's subjects were positive for Candida, while the other two tests indicated that 83% were positive. CONCLUSION: The Latex Candida technique was comparable to Oricult and streptomycin-vancomycin culturing techniques for negative results and was correctly positive for 90% of cases.

Adult↗

Heteroduplex mobility assay of the 26S rDNA D1/D2 region for differentiation of clinically relevant Candida species.

The Heteroduplex Mobility Assay (HMA) method using the PCR amplified D1/D2 region of the 26S rDNA was tested for the differentiation of clinically relevant Candida species. Strains belonging to the same species are not expected to form heteroduplexes in this assay when their PCR products are mixed. D1/D2 HMA experiments between all Candida type strains tested showed heteroduplex formation, including Candida albicans and Candida dubliniensis. There was no heteroduplex formation when most clinical and non-type strains were tested against the type strain of their presumptive species, except when C. albicans WVE and C. dubliniensis TAI were analysed. Additional HMA experiments, phenotypic characterisation, and D1/D2 sequencing identified these isolates as Candida tropicalis and Candida parapsilosis, respectively. HMA provides a rapid and relatively simple molecular tool for the differentiation of potentially pathogenic Candida species.

Base Sequence↗

Photosensitization of different Candida species by low power laser light.

The aim of this study was to evaluate the effects of the laser radiation (685 nm) associated with photosensitizers on viability of different species of Candida genus. Suspensions of Candida albicans, Candida dubliniensis, Candida krusei and Candida tropicalis, containing 10(6) viable cells per milliliter were obtained with the aid of a Neubauer's chamber. From each species, 10 samples of the cell suspension were irradiated with diode laser (685 nm) with 28 J/cm2 in the presence of methylene blue (0.1 mg/ml), 10 samples were only treated with methylene blue, 10 samples were irradiated with laser in the absence of the dye, 10 samples were treated with the dye and irradiated with laser light and 10 samples were exposed to neither the laser light nor to the methylene blue dye. From each sample, serial dilutions of 10(-2) and 10(-3) were obtained and aliquots of 0.1 ml of each dilution were plated in duplicate on Sabouraud dextrose agar. After incubation at 37 degrees C for 48 h, the number of colony-forming units (CFU/ml) was obtained and data were submitted to ANOVA and Tukey's test (p<0.05). Laser radiation in the presence of methylene blue reduced the number of CFU/ml in 88.6% for C. albicans, 84.8% for C. dubliniensis, 91.6% for C. krusei and 82.3% for C. tropicalis. Despite this, only laser radiation or methylene blue did not reduce significantly the number of CFU/ml of Candida samples, except for C. tropicalis. It could be concluded that the photo activation of methylene blue by the red laser radiation at 685 nm presented fungicide effect on all Candida species studied.

Candida↗

[Candida spondylitis. Case report and review of the literature].

Candida species have emerged as important pathogens in human infection. Although a variety of deep-seated candidal infections have been reported, Candida spondylitis has rarely been described. One patient with candida tropicalis spondylitis L I and L II in combination with candida coxitis is presented, and the 31 adult cases with vertebral involvement previously reported are reviewed. Candida spondylitis is noted as a simultaneous occurrence or late manifestation of hematogenously disseminated candidiasis. Spondylitis may not be prevented by a course of Amphotericin B adequate to control the acute episode of disseminated candidiasis, particularly in immune suppressed patients. Spondylitis does not present as a postoperative wound infection. The insidious progression of infection, the nonspecificity of laboratory data, and the failure to recognise Candida as a potential pathogen may lead to diagnostic delay. Diagnosis can be made by either open biopsy or CT controlled needle aspiration. Successful therapeutic regimes have employed combinations of antifungal therapy (Amphotericin B or fluconazole) with radical surgical debridement. Ventral and facultatively dorsal instrumentation is required to stabilize the spine. It is anticipated that the spondylitis will become a more commonly recognised manifestation of hematogenously disseminated candidiasis. A increasing significance of candida species as etiologic agents of infection immune compromised humans has been recognised in the recent years. In those patients whom an antecedent Candida septicaemia was documented, a striking delay of 3.3 months was found between the septicaemia and the onset of symptoms as well as the time of diagnosis.

Adult↗

Dexamethasone therapy and Candida sepsis in neonates less than 1250 grams.

OBJECTIVE: To determine whether dexamethasone use increases the risk for Candida sepsis (CS) in very low birth weight premature infants (<1250 g). DESIGN: Retrospective chart review of all infants with a birth weight <1250 g, admitted to the neonatal intensive care unit of the MetroHealth Medical Center, Cleveland, Ohio between January 1, 1996 and December 31, 1999. Infant groups with (n=65) and without (n=229) CS were compared. RESULTS: Two hundred and ninety four infants with a birth weight <1250 g were identified. CS was diagnosed at a median age of 18 days, and 6 of 65 (10%) infants died directly from Candida-related complications. Candida albicans (n=30, 60%) and Candida parapsilosis (n=14, 25%) were the predominant isolates. Use of dexamethasone in infants at risk for chronic lung disease before 14 days of age (p=0.001), duration of antibiotics (p=0.001), and total duration of parenteral nutrition and intralipid (p=0.0001) were all significantly greater in infants who developed CS. Regression analysis showed that duration of antibiotics before the diagnosis of Candida infection (r(2)=0.69, p=0.0002) and duration of dexamethasone (r(2)=0.93, p=0.0002) correlated with Candida infection. Early dexamethasone use was also related to the age at diagnosis of Candida infection (r(2)=0.51, p=0.01). CONCLUSIONS: Dexamethasone therapy and prolonged duration of antibiotics are associated with Candida infection in premature infants.

Candidiasis↗

Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures.

OBJECTIVE: The purpose of this study was to examine the frequency of normal cerebrospinal fluid (CSF) parameters in Candida meningitis and the proportion of candidemia associated with Candida meningitis. STUDY DESIGN: We evaluated the initial lumbar puncture results from infants discharged from 150 Neonatal Intensive Care Units between 1997 and 2004. Candida meningitis was diagnosed by a positive CSF culture or positive Gram stain for yeast. We calculated two-tailed P-values using non-parametric testing, Mann-Whitney, Kruskal-Wallis or Fisher's exact tests where appropriate. RESULTS: Twenty infants had culture-positive Candida meningitis. Normal CSF parameters were found in 43% (3/7) of the infants with Candida meningitis and only 37% (7/19) of them had positive blood cultures for Candida. CONCLUSION: Normal CSF parameters do not exclude the diagnosis of neonatal Candida meningitis. The majority of infants in this cohort with Candida meningitis did not have evidence of candidemia at the time of diagnosis.

Blood Glucose↗

Antifungal resistance in non- albicans Candida species.

Non- Candida albicans species have emerged as important bloodstream pathogens. They tend to have decreased susceptibility to antifungal agents in vitro and cause infections associated with high morbidity and mortality. Fluconazole resistance can emerge in any Candida spp., but is most commonly seen with Candida krusei, for which resistance is universal, and with Candida glabrata. Amphotericin B resistance has also been increasingly reported, most notably in isolates of Candida lusitaniae and Candida guilliermondii. Efforts are underway to correlate in-vitro antifungal susceptibility of individual Candida isolates with response to therapy of patients with candidemia. Future advances in this field might allow physicians to identify Candida isolates resistant to specific antifungal agents and thereby tailor therapy of candidemia. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗

Cross-sectional study of oral Candida carriage in a human immunodeficiency virus (HIV)-seropositive population: predisposing factors, epidemiology and antifungal susceptibility.

The Candida species isolated from oral rinses of 130 human immunodeficiency virus (HIV) infected patients were compared with those of 130 healthy non-matched volunteers. The oral rinses were plated on CHROMagar Candida medium (CAC) and on CAC supplemented with 10 micrograms (CF10) and 100 micrograms (CF100) of fluconazole per ml. The prevalence of non-albicans Candida spp. in oral rinses of HIV-infected patients and their correlation with the clinical and epidemiological characteristics of the patients were studied. Susceptibility of the Candida spp. isolated was determined by a microbroth dilution method based on the NCCLS reference procedure. Results of susceptibility tests of the yeast isolates were compared with their growth at the time of isolation on CAC supplemented with fluconazole. Thirty-five (30.7%) strains of non-albicans Candida spp. were isolated from the HIV-positive population, vs. seven (15.9%) from the immunocompetent population. Growth on CF10 correlated in 96% of the cases with fluconazole minimum inhibitory concentration (MIC) > 8 micrograms ml-1. Smoking and use of azoles were significantly associated with oral carriage of non-albicans Candida spp. (P < 0.05). The prevalence of non-albicans Candida spp. in HIV-positive persons in oral rinse samples is twice as high as in the HIV-negative population. Smoking and treatment with azoles are risk factors for the oral carriage of non-albicans Candida spp. The isolation of yeasts on CAC plates supplemented with fluconazole allows combination of presumptive yeast identification and fluconazole susceptibility testing.

Adult↗

[Candida in dermatology].

Regarding Candida in dermatology, two pathogenetic pathways must be taken into account: 1. on infection of the skin 2. immunological reactions with skin alterations as a result of Candida infection or colonization in the mouth and/or intestine. Case reports describe typical situations of napkin dermatitis, intertriginous candidosis, the intrauterine Candida infection of the foetus, Candida granuloma, Candida folliculitis and Candida paronychia. In the second part results of investigations of patients suffering from psoriasis, atopic dermatitis and urticaria are presented. There were no differences in the colonization with Candida albicans and in the level of Candida antibody titres between patients and a healthy control group.

Adult↗

Flow cytometry antifungal susceptibility testing of pathogenic yeasts other than Candida albicans and comparison with the NCCLS broth microdilution test.

Candida species other than Candida albicans frequently cause nosocomial infections in immunocompromised patients. Some of these pathogens have either variable susceptibility patterns or intrinsic resistance against common azoles. The availability of a rapid and reproducible susceptibility-testing method is likely to help in the selection of an appropriate regimen for therapy. A flow cytometry (FC) method was used in the present study for susceptibility testing of Candida glabrata, Candida guilliermondii, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, and Cryptococcus neoformans based on accumulation of the DNA binding dye propidium iodide (PI). The results were compared with MIC results obtained for amphotericin B and fluconazole using the NCCLS broth microdilution method (M27-A). For FC, the yeast inoculum was prepared spectrophotometrically, the drugs were diluted in either RPMI 1640 or yeast nitrogen base containing 1% dextrose, and yeast samples and drug dilutions were incubated with amphotericin B and fluconazole, respectively, for 4 to 6 h. Sodium deoxycholate and PI were added at the end of incubation, and fluorescence was measured with a FACScan flow cytometer (Becton Dickinson). The lowest drug concentration that showed a 50% increase in mean channel fluorescence compared to that of the growth control was designated the MIC. All tests were repeated once. The MICs obtained by FC for all yeast isolates except C. lusitaniae were in very good agreement (within 1 dilution) of the results of the NCCLS broth microdilution method. Paired t test values were not statistically significant (P = 0.377 for amphotericin B; P = 0.383 for fluconazole). Exceptionally, C. lusitaniae isolates showed higher MICs (2 dilutions or more) than in the corresponding NCCLS broth microdilution method for amphotericin B. Overall, FC antifungal susceptibility testing provided rapid, reproducible results that were statistically comparable to those obtained with the NCCLS method.

Amphotericin B↗

Deregulated production of protective cytokines in response to Candida albicans infection in patients with chronic mucocutaneous candidiasis.

Patients with chronic mucocutaneous candidiasis (CMC) are selectively unable to clear the yeast Candida, which results in persistent debilitating infections affecting the skin, nails, and mucous membranes. The underlying defect is unknown. Recent animal studies highlighted the importance of type 1 cytokines in protection against Candida, and previous work suggested that CMC patients may exhibit altered cytokine production in response to Candida. Based on these findings, in this study we investigated cytokine production in CMC patients by assessing a range of inflammatory, anti-inflammatory, type 1, and type 2 cytokines (interleukin-2 [IL-2], IL-4, IL-5, IL-6, IL-10, IL-12, gamma interferon [IFN-gamma], tumor necrosis factor alpha [TNF-alpha]) in whole-blood cultures in response to five different fractions of Candida albicans (carbohydrate, purified mannan, and protein-rich fractions, etc.), as well as non-Candida antigens. Our results demonstrate that cytokine production is deregulated in a Candida-specific way for some cytokines (IL-2, IL-10), is deregulated more generally for other cytokines (IL-12, IL-6, IFN-gamma), and is not markedly altered for still other cytokines (TNF-alpha, IL-4, IL-5). The most notable finding in CMC patients was the markedly impaired production of IL-12 in parallel with dramatically increased levels of IL-6 and IL-10 that occurred selectively in response to Candida. These results suggest that patients with CMC have impaired production of type 1-inducing cytokines (possibly a macrophage or dendritic cell defect?), which could result in an inability to mount protective cell-mediated responses and a failure to clear Candida. Continued tissue damage and inflammation may trigger production of high levels of inhibitory cytokines, such as the IL-10 production seen in our study, which would further reduce production of type 1-inducing cytokines in a positive feedback loop leading to persistent infection.

Adolescent↗

Identification of Candida species in formalin fixed, paraffin wax embedded oral mucosa by sequencing of ribosomal DNA.

Aim-To identify Candida species in formalin fixed, paraffin wax embedded tissue by sequencing candidal rDNA.Methods-Target rDNA sequences were amplified by polymerase chain reaction (PCR) from fresh isolates of Candida and from 18 preserved oral mucosal tissue samples (16 cases of chronic hyperplastic candidiasis and two fibroepithelial polyps), shown histologically to contain Candida. Identification of Candida species within tissue was based on a comparison of the rDNA sequences obtained with those from the fresh isolates of Candida and those present in the GenBank database.Results-The PCR products obtained from 12 of the 18 tissue specimens studied were characteristic of Candida albicans. In two of these cases a second, larger PCR product was obtained and these sequences were characteristic of Candida glabrata.Conclusions-Candidal DNA was amplified successfully from formalin fixed, paraffin wax embedded tissue. Sequencing of the PCR product enabled identification of the Candida species present.

Journal Article↗