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PubMed1997

Candida albicans morphogenesis is influenced by estrogen.

Conversion of Candida albicans from yeast to mycelial growth is believed to be associated with the organism's virulence. We investigated the role of mammalian hormones in initiating this transformation. Three clinical isolates of Candida albicans were tested for their ability to produce germ tubes under various conditions. Controlled hormonal conditions were provided by stripping rabbit serum with activated charcoal. Steroid compounds under investigation were added back to the stripped serum and yeast were inoculated into the test materials. Microscopic counts of germinated versus ungerminated cells were used as an indicator of morphogenic transformation. The percent of yeast cells germinating was profoundly reduced in stripped compared to unstripped serum. The addition of 1 microM estradiol, cholesterol or testosterone only slightly increased levels of germination above that seen in controls. Estradiol at concentrations 100 times less, however, proved a strong inducer of germination. Cholesterol did not synergize germination when combined with estradiol and the alpha isomer of estradiol had almost no activity as an inducer of morphogenic change in Candida albicans. We conclude that beta estradiol was a morphogenic inducer in three clinical isolates of Candida albicans but only at concentrations typical in vivo.

Animals↗
PubMed2001

Value of Candida antigen and antibody assays for the diagnosis of invasive candidosis in surgical intensive care patients.

During a 3-year period, a clinical diagnosis of invasive candidosis was made in 8 out of 2054 consecutive surgical intensive care unit (ICU) patients. These patients were retrospectively matched with 16 control patients who underwent similar surgical procedures and had a similar clinical course except for negative Candida cultures. In all patients, Candida antigen (Ramco CandTec serum antigen test) and antibody serology (Candida HA test) were determined at least once a week during their stay. The antigen test was positive in 1/8 patients and 4/16 controls and thus did not differentiate patients with candidosis from non-infected controls. The HA antibody titer results fulfilled the manufacturer's criteria for positivity in 7/8 patients with candidosis and 2/16 control patients. Thus, the Candida HA antibody test, but not the Ramco antigen test, can be recommended to confirm a clinical diagnosis of invasive candidosis.

APACHE↗
PubMed2003

Two cases of systemic Candida glabrata infection following in vitro fertilization and embryo transfer.

Presented here are two cases of systemic Candida glabrata infection diagnosed in two expectant mothers and their fetuses at 34 and 22 weeks' gestation. The underlying risk factors in case 1 were in vitro fertilization and embryo transfer, recurrent yeast vaginitis and two intravenous injections of betamethasone. The risk factors in case 2 were in vitro fertilization and embryo transfer, recurrent yeast vaginitis, antibiotics for treatment of a urinary tract infection due to Morganella morganii and amniocentesis. In both cases, vaginal fluid yielded growth of a yeast that was not identified. Candida glabrata was isolated from samples obtained from the mothers and their babies. Since Candida glabrata lacks hyphae, membranitis and infection of the fetuses were demonstrated only on slides stained with Gomori Grocott and periodic acid-Schiff. Both cases suggest that for such pregnancies the follow-up of vaginal fluid should include the identification of any yeasts grown on selective Candida medium. In case of premature rupture of membranes, systematic sampling of mothers and their infants or fetuses should be associated with microscopic study of placentas, membranes and stillborn fetuses with Gomori Grocott and periodic acid-Schiff staining techniques.

Adult↗
PubMed1999

Susceptibility of Candida species isolated from female prostitutes with vulvovaginitis to antifungal agents and boric acid.

The aim of this study was to determine the antifungal susceptibility of 108 Candida albicans and 23 Candida glabrata isolates obtained from female prostitutes with vulvovaginitis, a population for which available data is limited. Amphotericin B, flucytosine, and fluconazole were tested by broth microdilution, and boric acid was tested by the agar dilution method. The susceptibility patterns found in this population were the same as those in the general population. Candida glabrata required greater concentrations of boric acid for inhibition in vitro than did Candida albicans.

Antifungal Agents↗
PubMed1999

Comparative in vitro activity of voriconazole and itraconazole against fluconazole-susceptible and fluconazole-resistant clinical isolates of Candida species from Spain.

The in vitro activity of voriconazole was compared with that of itraconazole against 299 fluconazole-susceptible (MIC < or = 8 microg/ml) and 130 fluconazole-resistant (MIC > or = 16 microg/ml) clinical isolates of Candida spp. An adaptation of the National Committee for Clinical Laboratory Standards reference method was employed for determination of MICs. Voriconazole showed more potent activity than either fluconazole and itraconazole, even against some Candida albicans, Candida glabrata, and Candida krusei isolates resistant to fluconazole. However, for fluconazole-resistant isolates, the MICs of itraconazole and voriconazole were proportionally higher than for fluconazole-susceptible isolates. These data may indicate cross-resistance.

Antifungal Agents↗
PubMed2004

Augmented inhibition of Candida albicans growth by murine neutrophils in the presence of a tryptophan metabolite, picolinic acid.

The effects of picolinic acid (PLA), a product of tryptophan catabolism, on anti- Candida activity of neutrophils were studied. Casein-induced peritoneal neutrophils of C3H/He mice partially inhibited mycelial growth of Candida albicans when cultured with C. albicans for 16 h in vitro. The growth inhibition of Candida was augmented by a combination of neutrophils and more than 4 mM picolinic acid. Especially in the presence of 200 U/ml murine interferon-gamma (IFN-gamma), 2 mM picolinic acid augmented the anti- Candida activity of neutrophils. The physiological significance of the augmenting effects of picolinic acid is discussed.

Animals↗
PubMed2001

Nosocomial fungemia due to amphotericin B-resistant Candida spp. in three pediatric patients after previous neurosurgery for brain tumors.

Amphotericin B (AmB) resistance in Candida spp. is very rare. Three cases of fungemia, due to amphotericin B-resistant Candida spp. in pediatric patients after previous neurosurgery for brain tumors, are reported. The Candida strains - one C. guillermondii, one C. lusitaniae, and one C. parapsilosis - showed minimum inhibitory concentrations (MICs) to AmB of 2-4 microg/ml. Two of the three patients had been pretreated with AmB for 5-11 days. All three patients were successfully treated with intravenous fluconazole (6-10 mg/kg per day) for 16-28 days, and all survived. Despite AmB resistance in Candida spp. being very rare, C. lusitaniae, C. guillermondii, and C. parapsilosis isolates in documented infections should be tested for AmB resistance, mainly in patients not responding to therapy with AmB.

Adolescent↗
PubMed2004

Prosthetic valve endocarditis due to Candida albicans treated successfully with medical treatment alone.

Prosthetic valve endocarditis (PVE) caused by Candida species is associated with high morbidity and mortality. A combination of surgical resection and antifungal drug therapy is the golden standard for treatment, yet surgical intervention is not possible in all cases of Candida PVE. We report a case of PVE due to Candida albicans cured by medical treatment alone. This case suggests that, in some instances, Candida PVE can be managed medically with antifungal therapy. Such a conservative approach should be applied with caution and necessitates very close follow-up on a long-term basis.

Amphotericin B↗
PubMed1989

Candida albicans: cellular immune system interactions during different stages of the menstrual cycle.

Candidal vaginitis most often recurs during pregnancy and in the late luteal phase just before menstruation. We examined the influence of the stage of the menstrual cycle on the cellular immune response to Candida albicans, the efficiency of C. albicans germination in sera, and the ability of products from activated lymphoid cells to inhibit germination. C. albicans germination was maximal in sera obtained during the luteal phase. During this period the cellular immune response to Candida was reduced as was the inhibition of Candida germination by products of activated peripheral blood mononuclear cells. Variations in immune response to Candida were of much lesser magnitude in women who took oral contraceptives, which suggests that it was the marked fluctuation in progesterone or estradiol levels during the menstrual cycle that influenced the changes in the immune response to C. albicans. Thus the hormonal status of women may influence the pathogenicity of C. albicans by modulation of immune system activity. These results explain the clinical observation that candidal vaginitis infections most frequently reappear before menstruation.

Adult↗
PubMed1987

Epidemiology of vaginal Candida infection: significance of numbers of vaginal yeasts and their biotypes.

The prevalence, quantity and biotypes of vaginal yeasts were determined for 1082 randomly selected nonpregnant patients attending two genitourinary medicine clinics. The overall yeast prevalence was 22.1% with a geometric mean of 40 and a median of 75 yeast colonies per positive isolate (on 5-cm Petri dishes). There was no statistically significant variation in prevalence, quantity or biotype of yeasts with the patients' age, season of the year, stage of the menstrual cycle, recent antibiotic history, contraceptive use or main diagnosis (excluding candidosis). A clinical score for Candida infection, based on symptoms of pruritus and signs of Candida vulvovaginitis, showed significant variation with the prevalence and quantity of yeast isolates. Unequivocal clinical evidence of candidosis was strongly associated with high concentrations of vaginal yeasts. There was also some association between certain groups of Candida albicans biotypes and the clinical score. These observations reemphasize the need for consideration of both clinical and mycological factors in establishing a diagnosis of vulvovaginal Candida infection. It is suggested that isolation of fewer than 10 yeast colonies from a vaginal swab is usually unlikely to indicate an infection requiring treatment.

Age Factors↗
PubMed1977

The effect of chlorhexidine mouth rinses on oral Candida in a group of leukemic patients.

Eighteen leukemic patients were examined for the presence of Candida albicans in the oral cavity. Fifteen patients were found to be Candida "carriers." Nine of the patients were put on a chlorhexidine mouth rinse regimen. Although chlorhexidine was clearly fungicidal in vitro, no decrease in Candida titer was obtained with the mouth rinse. The ineffectiveness of the drug in vivo might be due to the specific location of Candida organisms in the oral mucosa.

Biguanides↗
PubMed1993

Oral carriage of Candida in healthy and HIV-seropositive persons.

The prevalence of oral colonization with Candida species was studied in 28 HIV-seropositive and 28 healthy persons. Candida was cultured from 75% and 68% of HIV-positive and control persons, respectively, with a significantly higher density carriage in the HIV-seropositive group. Positive smears were seen in 39% of all patients. Candida albicans was the most frequently isolated species with Biotype 1 accounting for 56% of the isolates. Resistance to antifungal agents was seen in Candida strains isolated from both groups.

AIDS-Related Opportunistic Infections↗
PubMed1982

Immunochemical determinant and serological specificity of Candida krusei.

We have investigated the chemical structure of the antigenic determinant of Candida krusei cell-wall mannan. Acetolysis of the mannan, obtained by extraction with alkali and purified as copper complex, gave five oligosaccharides (from mono- to pentasaccharide) and a minor amount of an octasaccharide. Partial acetolysis of the mannan gave a large amount of mannooctaose. We have examined the inhibition by these oligosaccharides of the precipitin reaction between anti-Candida krusei serum and homologous mannan, and found that the mannooctaose was the most effective inhibitor. Results obtained by proton magnetic resonance spectroscopy, methylation analysis, and other structural studies of Candida krusei mannan, suggest that the octasaccharide possesses six alpha (1-2) linkages and one alpha (1-6) linkage located in the middle of the chain, and that this mannooctaose may be responsible for the specificity of Candida krusei cell-wall mannan.

Antigens, Fungal↗
PubMed1996

Effect of d-fenfluramine on the local immune response to the opportunistic microbial pathogen Candida albicans.

In this study the effects of systemic administration of d-fenfluramine on the local lymphocyte response to Candida albicans was evaluated. Experimental animals were challenged intradermally with Candida albicans and then administered d-fenfluramine (d-FEN 1 mg/kg per day, i.p.) or a balanced salts solution. At successive time intervals, lymphocytes were derived from the draining lymph nodes and from the dermal sites of active microbial challenge. A CD8+ lymphocytosis was observed in all animals challenged with Candida albicans. The CD8+ lymphocytosis was augmented in animals that received d-FEN. Phenotypically, lymph nodes from d-FEN treated animals showed a marked increase in CD3+ and CD8+ lymphocytes, a modest increase in the numbers of NK1.1+ cells and a decrease in Ig+ lymphocytes. Functionally, lymphocytes from the site of active microbial challenge were capable of direct growth inhibition of Candida albicans. The anti-fungal activity was augmented in the animals that received d-FEN. These results suggest that d-FEN augments the local T lymphocyte response to an important microbial pathogen by increasing the number of T lymphocytes draining the site of microbial infection and by increasing the biological activity of the lymphocytes at the site of the infection.

Animals↗
PubMed1983

Cloning of a LEU gene and an ARS site of Candida maltosa.

Gene libraries of DNA from an n-alkane-assimilating yeast strain, Candida maltosa IAM12247, were constructed, using Escherichia coli plasmid vector pBR322. A LEU gene from C. maltosa was cloned, and found to complement leu- mutations in E. coli and Saccharomyces cerevisiae. In E. coli, the LEU gene in the cloned yeast DNA fragment was efficiently expressed when inserted into the vector in one orientation, while in the other orientation, it was expressed only weakly. In S. cerevisiae, the Candida LEU gene was efficiently expressed when inserted into a shuttle vector pRC3 in both orientations, suggesting that the isolated Candida DNA fragment contains a promoter sequence of Candida in front of the LEU gene, which is operative in S. cerevisiae but not in E. coli. In addition, our data suggest that the cloned LEU fragment also contains an ARS (autonomously replicating sequence) site of C. maltosa.

Candida↗
PubMed1990

Cloning and characterization of the 2,3-oxidosqualene cyclase-coding gene of Candida albicans.

2,3-Oxidosqualene (OS) cyclase (OSC) catalyzes the conversion of OS to lanosterol, an essential step in the biosynthesis of sterols. The Candida albicans gene (ERG7) encoding OSC was cloned by complementation of a Saccharomyces cerevisiae OSC mutant (erg7). Two different Erg+ clones were isolated that contain a common overlapping region. The minimum region required for complementation was determined to be approx. 3.2 kb and a single 2.7-kb ERG7 transcript was detected. The cloned Candida ERG7 DNA complemented an additional nonconditional erg7 allele and a temperature-sensitive erg7 mutation. OSC activity was restored in the mutants as determined by [14C]acetate incorporation in vivo as well as incorporation in vitro in cell-free extracts using either [14C]isopentenyl pyrophosphate or [3H]OS as substrate. The level of OSC produced from expression of a single copy of the Candida ERG7 sequence was sufficient to allow growth of the S. cerevisiae erg7 mutants in the absence of exogenous ergosterol. These data support the contention that the Candida ERG7 sequence is the structural gene for OSC.

Alleles↗
PubMed1988

Development of DNA probes for Candida albicans.

An attempt was made to produce DNA probes that could be used as a rapid and efficient means of detecting candidiasis (invasive Candida infection) in immunocompromised patients. Whole DNA from Candida albicans was digested with restriction endonuclease, and the resulting fragments were randomly cloned into a plasmid vector. Several recombinant plasmids were evaluated for cross-hybridization to various other Candida species, other fungal DNAs, and to nonfungal DNAs. Cross reactions were observed between the probes and different yeasts, but none with unrelated DNAs. Some recombinants were genus-specific, and two of these were applied to the analysis of C. albicans growth curves. It became evident that, although both 32P- and biotin-labelled probes could be made quite sensitive, a possible limitation in their diagnostic potential was the poor liberation of Candida DNA from cells. Thus, better methods of treatment of clinical specimens will be required before such probes will be useful in routine diagnosis.

Autoradiography↗
PubMed2005

Treatment of non-albicans Candida vaginitis with amphotericin B vaginal suppositories.

OBJECTIVE: This study was undertaken to investigate whether amphotericin B vaginal suppositories would be effective in the treatment of non- albicans Candida vaginitis in women who failed conventional therapy. STUDY DESIGN: Thirty-two patients were identified with non- albicans Candida vaginitis. These patients were treated with conventional antifungal agents. Ten patients had persistence of the non- albicans Candida infection after treatment. Amphotericin B 50-mg vaginal suppositories were given nightly for 14 days to this subgroup of treatment failures. RESULTS: Of 10 women, 8 (80%) who were treated with amphotericin B vaginally initially showed no further infection. One of the treatment successes had 2 recurrences and responded to a second course of amphotericin B but failed a third course. If this patient is considered a treatment failure, then amphotericin B vaginal suppositories were successful in 70% of patients. The medication was well tolerated and local side effects were minimal. CONCLUSION: Amphotericin B vaginal suppositories are a viable treatment option for refractory vaginitis caused by non- albicans Candida .

Administration, Intravaginal↗