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PubMed2000

Surveillance of the serum Candida antigen titer for initiation of antifungal therapy after post-remission chemotherapy in patients with acute leukemia.

The early diagnostic efficacy of serial Candida antigen detection by the assay kit CAND-TEC (a latex particle agglutination test) was evaluated in 12 episodes in 10 patients with acute leukemia after post-remission chemotherapy. To determine the timing to initiate antifungal chemotherapy, we performed the CAND-TEC assay serially in each patient. When the patients revealed febrile neutropenia after antileukemic chemotherapy and the Candida antigen titer was increased compared to that measured before the antileukemic chemotherapy (even if the increased titer was at a lower level, e.g., from negative to 1:1 positive or from 1:1 to 1:2), azole antifungal agents (fluconazole or miconazole) were administered intravenously. In 9 (81.8%) of the 11 evaluable cases, the antifungal chemotherapy was effective and the titers decreased to less than or equal to the previous titers in all cases. In 2 cases, the antifungal chemotherapy was not effective, and the titers did not decrease. These results suggest that serial Candida antigen detection provides a useful method in the early diagnosis of invasive candidiasis in febrile neutropenia and in determining the timing of the initiation of early antifungal chemotherapy. This method might also be useful in preventing the excess use of antifungal agents; thus preventing the proliferation of azole-resistant Candida infection.

Acute Disease↗
PubMed2000

[Susceptibility to fluconazole and itraconazole in isolates of Candida spp. from HIV-positive and HIV-negative patients].

We studied the possible differences in the pattern of susceptibility to fluconazole and itraconazole in 393 isolates of Candida spp. from the oral cavity of HIV-positive patients and 102 isolates from HIV-negative patients with candidemia or candiduria. We used the broth microdilution method according to the NCCLS guidelines. We observed a decrease in the susceptibility to fluconazole in the group of HIV-positive patients in comparison to those who were HIV negative, especially in Candida albicans (MIC(90) 32 mg/l vs. 1 mg/l and Candida glabrata (MIC(90) 64 mg/l vs. 16 mg/l). Furthermore, we did not find any resistant strains in the HIV-negative group. For itraconazole, the MIC(90) was two dilutions greater in the HIV-positive patients, except for C. albicans, which had a much higher MIC(90) (4 mg/l vs. 0.12 mg/.). Therefore, the decrease in the susceptibility of Candida spp. in the HIV-positive patients must be taken into account when establishing a specific antifungal therapy.

Antifungal Agents↗
PubMed1975

Relationship among skin tests, bronchial challenge and serology in house dust and Candida albicans allergic asthma.

One hundred and ninety-six asthmatic patients were examined by inhalation challenge using house dust and candida albicans; an early, dual or late bronchial response was induced where IgE, C3 and C4 were elevated. In some of late responses by candida inhalation there was a decrease or almost no increase in IgE and a fall in C3 and C4. There was a considerable correlation between skin tests and bronchial responses. An induced bronchial response, early, dual or late, was identified as Type I, While candida-induced late bronchial responses were Type I and Type III. There is some question whether Type I plus Type III mechanism may be involved in the dual bronchial response provoked with candida.

Adolescent↗
PubMed2000

Deep Candida infections in the neutropenic and non-neutropenic host: an ISHAM symposium.

A symposium was held on May 8, 2000 to discuss the management of deep infections with Candida species. Among the findings discussed were the following. Candiduria is most often benign, though it occurs in patients with serious underlying diseases. Candida species are now the fourth most common cause of nosocomial bloodstream infections, usually arising from an intravenous catheter. Candida albicans represents only 50-60% of the isolates. There has been no change in the frequency of fluconazole resistance in C. albicans but some of the other species now being isolated from blood are constitutively more resistant to this drug. Nevertheless, for most non-neutropenic patients with candidemia, fluconazole is a reasonable choice for initial therapy. In the neutropenic patient, candidemia is now uncommon. Deep candida infections in neutropenic patients are usually being treated empirically with an amphotericin B formulation. Hepatosplenic candidiasis is usually detected only after recovery from neutropenia but can be suspected by imaging techniques. Improved diagnostic techniques for deep candidiasis in the neutropenic patient remain a critical requirement.

Antifungal Agents↗
PubMed2000

[Candida antigen and antibody kinetics during antifungal therapy in non-neutropenic intensive care patients].

The present study aimed at determining Candida antigen and antibody kinetics during antifungal therapy. 115 non-neutropenic patients with a stay of more than 5 days in an interdisciplinary intensive care unit during a period of 2 years were reviewed. Routinely measured Candida antigen and antibody titers were evaluated at the beginning and during antifungal therapy. In 67 patients serological data were evaluable in defined time slots. Under fluconazole therapy (FT) the median of Candida antigen (Ramco) was 1:4 and did not change significantly. Candida antibody level increased from 1:80 to 1:320. Initial titers between FT and amphotericin B/5-fluorocytosine therapy (AT) showed a significant difference. During AT antigen titers decreased from 1:8 to 1:4 while antibody titers kept constant at a level of 1:160.

Amphotericin B↗
PubMed2001

[Diagnosis of normal and abnormal delayed hypersensitivity to Candida albicans. Importance of evaluating lymphocyte activation by flow cytometry].

Delayed type hypersensitivity (DTH) to Candida albicans is commonly observed in human. Abnormal DTH has already been described but its diagnosis is difficult to ascertain. We present now a clinical and biological study in 60 patients with a clear distinction between these two kind of Candida albicans DTH. Clinical abnormal Candida albicans DTH was characterized by a syndromic reaction 24 to 48 hours after intradermal injection. This reaction was characterized by an exacerbation of clinical symptoms. In vitro, activation of whole blood with Candida albicans antigen was detected by using flow cytometry after staining for activating markers. CD 25 positive T cells were detected in a 7 days culture in all patients. Percentage of CD 25 positive T cells was correlated to the intensity of the local cutaneous DTH reaction. CD 69 positive T cells were detected after a one day culture only in patient who presented a syndromic reaction to intradermal injection.

Adolescent↗
PubMed2001

Predictive value of Candida colonization index in 131 patients undergoing two different cardiovascular surgical procedures.

BACKGROUND: Nosocomial candidemia is an important infection because of its increasing incidence and its high fatality rate. Candidiasis involves multiple risk factors. In this work, we study the degree of Candida colonization in cardiovascular surgical patients by taking into account the number of sites colonized and the density of growth. METHODS: Eleven (11) selected variables (age, sex, weight, diabetes, number of antibiotics, duration of antibiotics, length of hospitalization, length of stay in surgical intensive care unit, duration of surgery, temperature during surgery, and number of bypass) were considered to predict the perioperative variation of the colonization index (CI) by Candida in 131 cardiovascular surgical patients. These patients were divided into two groups: group A, coronary artery bypass grafting with extracorporeal circulation (72 patients) and group B, coronary artery bypass grafting without extracorporeal circulation (59 patients). RESULTS: One thousand and forty-eight fungal cultures were obtained from four different body sites and 162 isolated were identified. Candida albicans accounted for 74% of the strains in group A and 97% in group B. The statistical analysis (two-way anova) shows that group A patients with an increased CI have received significantly more antibiotics than those with a stable CI (1.50+/-0.83 vs 1.08+/- 0.40, p=0.0055). CONCLUSIONS: Epidemiological data obtained from this study show that coronary artery bypass grafting with extracorporeal circulation procedure is associated with an increase in the use of antibiotics and subsequently a higher risk a Candida colonization-infection.

Aged↗
PubMed1998

[Synthesis and anti-Candida albicans properties of L-4-oxalysine-N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic-containing peptide analogues].

In order to improve the inhibitory activity of L-4-oxalysine(abbreviated as I-677) against clinically important pathogen Candida albicans, double-warheads peptide analogues containing I-677 and N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic acid(FMDP) were designed based on the concept of "Illicit Transport" and peptide transport specificities of C. albicans. One compound of I-677-FMDP and seven compounds of I-677-AA-FMDP(AA = Nva, Leu, Val, Phe, Pro, D-Pgly, D, L-p-Cl-Phe) were synthesized and examined for antifungal activities. The results of anti-Candida albicans test in vitro of these double- warheads peptide analogues containing I-677 and FMDP showed very high activities against Candida albicans. The molar MIC (molar minimum inhibitory concentration) ratio of free I-677 to I-677-AA-FMDP is 40-770 and that of FMDP is 60-1130. The values of molar MIC of I-677-AA-FMDP varied from 6.56 x 10(-9) mol.disk-1 to 3.5 x 10(-10) mol.disk-1. The results of competitive antagonism studies indicated that I-677-AA-FMDP were transported into Candida albicans cells by the di-tripeptide permease and subsequently hydrolyzed by intracellular peptidases, releasing free I-677 and FMDP inside cells. The result of antienzymic degradation test in vitro of I-677-FMDP showed that compound I-677-FMDP was resistant to the hydrolysis by carboxypeptidase A.

Animals↗
PubMed2002

The Lactobacilli--Candida relationship in cervico-vaginal smears.

The aim of this study is to determine whether there is a relationship between the presence of Lactobacilli and the growth of Candida. For this purpose, 1110 cervico-vaginal smears were examined cytologically and 450 patients who were normally menstruating were subsequently selected among them. Fifty nine of 450 were diagnosed as having Candida and they were accepted as study group. Three hundred and ninety-one patients who were diagnosed as having no infectious agents were accepted as control group. Lactobacilli were present in 50 of 59 in various degree and were absent in 9 of 59. The prevalence rates of the presence of Lactobacilli (84.74%) as well as intermediate cells (98.30%) were higher in study group than in control group. There was also a significant correlation between the presence of Lactobacilli and the growth of Candida (p < 0.05). Statistical analysis was performed with chi 2 test using SPSS package programme. We can suggest that Lactobacilli do not have a protective role when there is Candida growth in the vaginal mucosa.

Adult↗
PubMed2002

Anti-Candida antibodies in serum and saliva of patients with denture stomatitis.

OBJECTIVE: Quantitative measurement of IgA and IgG antibodies in the serum and saliva of patients with denture stomatitis (stomatitis subprothetica) was the object of this study. METHODS: The indirect immunofluorescence technique (IFA) utilizing CIP 628 (serotype A) Candida albicans blastospores was employed. Anti-human goat and rabbit fluorescein isothiocyanate labeled serum was used. Serial serum dilutions from 1:20 to 1:1280 and saliva serial dilutions from 1:1 to 1:8 were prepared. Specimens were read using an ML-2 fluorescence microscope. Alternative analysis, analysis of variance and graphical analysis was used for statistical analysis of data. RESULTS: Anti-Candida antibodies (mainly IgG class) were detectable at dilutions of 1:40, 1:80 and 1:160 in the serum of patients with denture stomatitis compared with healthy controls. The saliva samples of these patients showed higher titers of anti-Candida antibodies compared with controls (1:8 for IgG and 1:4 for IgA). CONCLUSIONS: IgG anti-bodies were prevalent in the saliva of our patients and they were of diagnostic value. The IgA titers did not remain constant and could be a determinant of the disease course. Each patient showed an individual serologic profile. For this reason individualized interpretation of saliva antibodies as well as a comparison with the serum anti-Candida antibodies is recommended.

Antibodies, Fungal↗
PubMed2003

[Study of the effects of alkali metals on some virulence characteristics of Candida albicans].

The effects of the alkali metals sodium, potassium and lithium on the growth and on certain virulence factors (adhesion, cell-surface hydrophobicity and the germinating ability) of Candida albicans were investigated. It can be concluded that high concentrations of alkali metals possessed an inhibitory effect on the growth of the Candida cells and preincubation in the presence of alkali metals had a negative effect on all the virulence factors studied. It is worth emphasizing that the changes induced during the preincubation persisted even when the high concentrations of the alkali metals were removed from the cell suspension. However, even at high concentrations of sodium or potassium a considerable growth of Candida cells could be measured. Data also showed that although alkali metals could significantly decrease certain virulence traits of the fungus they could not totally inhibit either the adhesion or the germ tube formation potential of the cells. Thus, in spite of the high salt concentrations Candida cells may represent a health hazard in such habitats.

Candida albicans↗
PubMedDate not supplied

[The value of the agar dilution method as a screening test for determining the sensitivity of Candida albicans to fluconazole].

The aim of this study was to evaluate the performance of agar dilution method in the determination of fluconazole susceptibility of Candida albicans strains, by using different culture media. Hundred and seven C. albicans strains which were isolated from different clinical specimens were included to this study and fluconazole susceptibilities were determined by both of the microdilution method according to NCCLS M-27A standards, and an agar dilution based method by using CHROMagar Candida and Biggy agar. For this purpose, CHROMagar Candida and Biggy agar plates containing 0 (as control plate), 8 and 16 micrograms fluconazole per mililiter were prepared and inoculated with standard amounts of 24 hours culture suspansions of C. albicans strains. The culture media were evaluated after incubation at 30 degrees C for 48 hours, and the growth of strains in the fluconazole-containing and fluconazole-free plates were compared. C. albicans strains were accepted susceptible if there were no growth or the colonies were smaller than control media, and resistant if the colonies were the same size as in the control media. As a result, 106 (99.1%) of the strains were found susceptible and one (0.9%) was found dose-dependent susceptible to fluconazole by microdilution method, whereas none of the isolates grew on 8 and 16 micrograms/ml fluconazole containing CHROMagar Candida and Biggy agar media. Therefore, the agar dilution test results of 106 strains (99.1%) were in agreement with the reference microdilution method. In conclusion, it was thought that agar dilution screening tests using two different culture media, were rapid and practical for routine use in the determination of fluconazole susceptibilities of C. albicans strains.

Antifungal Agents↗
PubMed1992

[Studies on IFN-gamma production by peripheral blood mononuclear cells cultured with Candida antigen in asthmatics].

T-cell-derived lymphokine, IFN-gamma, has potent effects on B-cell differentiation and leukotriene C4 production in leukocytes, and inhibits the effect of IL-4 on IgE production. To investigate the role of IFN-gamma in the pathogenesis of bronchial asthma, we examined IFN-gamma production by peripheral blood mononuclear cells cultured with Candida antigen and serum Candida specific IgG1 antibody from 20 asthmatics. The results were as follows: 1) IFN-gamma production in non-atopic severe asthmatics was significantly higher than in healthy subjects, atopic mild and moderate asthmatics, and atopic severe asthmatics (p < 0.05). 2) There was a significant correlation between IFN-gamma production induced by Candida antigen and serum Candida specific IgG1 antibody (r = 0.72, p < 0.01). These results suggest that IFN-gamma may play an important role in the pathogenesis of non-atopic severe bronchial asthma.

Adult↗
PubMed2003

[In vitro activity of fluconazole, voriconazole and posaconazole against Candida spp].

Voriconazole and posaconazole are two new triazoles with broad-spectrum antifungal activity. The in vitro activity of these agents was compared with that of fluconazole against 113 clinical isolates of Candida spp. exhibiting a wide range of MICs for fluconazole (< or =0.125 to >64 mg/l). They included 22 C. albicans isolates, 22 C. glabrata, 20 C. tropicalis, 15 C. dubliniensis, 13 C. parapsilosis, 13 C. krusei, 4 C. lusitaniae, 3 C. guilliermondii and 1 C. famata. MICs were determined by broth microdilution test performed according to the National Committee for Clinical Laboratory Standards' M27-A document. Voriconazole and posaconazole were quite active against all Candida spp. isolates, with MIC(90) of 0.25 and 0.5 mg/l, respectively. Fluconazole MIC(50) and MIC(90) were 1 and 32 mg/l. Voriconazole and posaconazole showed in vitro activity against fluconazole-susceptible and -resistant Candida isolates. Higher voriconazole and posaconazole MICs were observed in isolates exhibiting higher fluconazole MICs (>/=16 mg/l) than in those of fluconazole-susceptible isolates (MIC(90) for voriconazole and posaconazole in the fluconazole-resistant isolates were 0.5 mg/l versus 0.06 mg/l for voriconazole and 0.25 mg/l for posaconazole in the fluconazole-susceptible strains). C. dubliniensis was the most susceptible species, and voriconazole the most active antifungal agent against all Candida spp. tested.

Antifungal Agents↗
PubMed1992

Effect of amphotericin B alone or in combination with rifampicin on phagocytosis of Candida species by human polymorphonuclear leukocytes.

The influence of amphotericin B and rifampicin alone and in combination on the killing of Candida albicans, Candida tropicalis and Cryptococcus neoformans by human polymorphonuclear leukocytes was investigated in vitro. Granulocytes were harvested from the blood of healthy volunteers and resuspended with the above mentioned fungi. After 6 hours, 81.5% of C. albicans, 97% of C. tropicalis but only 34% of C. neoformans were killed. The activity of amphotericin B against C. albicans and C. tropicalis was better in granulocyte-free medium. A synergism between amphotericin B and rifampicin towards Candida could be detected. It was also demonstrated in the presence of polymorphonuclear leukocytes with a factor > 1 log in reduction of colony count. However, whether granulocytes were present or not, rifampicin (4 mcg/mL) alone did not exert any influence on growth of Candida.

Adult↗
PubMed1992

Susceptibility of Candida albicans to peroxidase-catalyzed oxidation products of thiocyanate, iodide and bromide.

The susceptibility of Candida albicans (ATCC 10231 and wild strains) to hypo(pseudo)halous ions (OSCN-, OBr-, OI-) produced by the lactoperoxidase system was tested. Six strains of Candida albicans were isolated from swabs taken from the mouths of children with orthodontic appliances and selected on Sabouraud-Chloramphenicol-Actidione agar plates. The survival rate of Candida blastospores after a 30 min exposure to lactoperoxidase system ranged from 79 to 105% in the presence of 615 microM thiocyanate, from 56 to 88% in the presence of 345 microM bromide and from 0 to 4% in the presence of 250 microM iodide. Results showed that only OI- could exert a strong inhibiting effect in vitro on Candida albicans at physiological concentrations. Nevertheless, the activity of the hypoiodite generating system in saliva was found to be under the control of thiocyanate concentration.

Acids↗
PubMed1992

In vitro, Candida albicans releases the immune modulator adenosine and a second, high-molecular weight agent that blocks neutrophil killing.

We previously described a lyophilized supernatant from germinated Candida albicans that blocks human neutrophil (PMN) O2- production and degranulation stimulated by several PMN agonists but does not block stimulation by PMA. In studies to further characterize this Candida hyphal inhibitory product (CHIP), we noted several physicochemical parallels with the purine nucleoside adenosine (Ado). A Sephadex G-10 semipurified fraction of CHIP had an absorption peak near 260 nm, an apparent m.w. of less than 400, and was resistant to boiling and proteases. Maximally effective doses of CHIP (100 micrograms/ml) and Ado (100 microM) blocked 0.1 microM FMLP-stimulated O2- production by 76.8 +/- 4.1 and 81.7 +/- 4.8%, respectively. Ado deaminase, known to inactivate Ado, reversed inhibition by both Ado and CHIP. Results were comparable for the effect of CHIP and Ado on FMLP-stimulated beta-glucuronidase and lactoferrin release. Activation of the respiratory burst by opsonized C. albicans yeast was also inhibited by CHIP and Ado, but the extent of inhibition was less than for FMLP. At yeast:PMN ratios of 4:1, 10:1, and 40:1, CHIP inhibited O2- by -3.8%, 14.3%, and 12.8%, respectively; Ado blocked production by 32.9%, 24.2%, and 11.5%, respectively. The effect of CHIP and Ado on Candida killing by PMN was compared using two viability assays in each of four experiments. Ado (100 microM) had no effect on killing, although CHIP (100 micrograms/ml) inhibited killing in the MTT assay at 15 and 45 min by 81.6 +/- 6.3 and 24.7 +/- 6.2%, respectively; as assayed by CFU, CHIP inhibited killing by 34.1 +/- 6.2 and 10.3 +/- 2.5%, respectively. The ability of CHIP to inhibit killing was not affected by adding Ado deaminase, providing additional evidence that an Ado-like effect by CHIP is not essential for killing inhibition. Killing of opsonized Streptococcus pneumoniae was also inhibited in a concentration-dependent manner. Reverse-phase HPLC of the semipurified fraction revealed a peak, eluting identically to authentic Ado, which was eliminated by adding Ado deaminase. Ado content of the G-10 fraction was sufficient to account fully for the FMLP-inhibitory activity. The antikilling activity was resistant to boiling and proteases but was eliminated by mild periodation. Fractions eluting from a Sephadex CL6B column between 0.8 and 2.0 x 10(6) m.w. had increased sp. act. for killing inhibition. Sp. act. increased as carbohydrate content increased, but killing inhibition by various Candida cell wall constituents was absent to modest compared to inhibition induced by CHIP.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗
PubMed2003

[Fluconazole resistance in Candida albicans assayed by PCR fingerprinting with M13 prime].

OBJECTIVE: To understand the molecular and genetic mechanism underlying fluconazole resistance in Candida albicans by PCR fingerprinting with M13 primer. METHODS: Paper disc diffusion method was employed for assay of fluconazole resistance in 41 clinical isolates of Candida albicans, followed by PCR fingerprinting with M13 primer to study the gel patterns with cluster analysis using neighbor joining (NJ) method performed with RAPD200 software. RESULTS: Of the 41 clinical isolates, 11 strains (26.8%) were fluconazole-sensitive, 8 (19.5%) fluconazole-dependent and 22 (53.7%) fluconazole-resistance. Two to twelve bands could be observed among these strains, and the gel patterns revealed by cluster analysis were associated with the reactions of the strains against fluconazole and the location of infection. CONCLUSION: There is high prevalence of fluconazole resistance in clinical Candida albicans isolates, and PCR fingerprinting with M13 primer is convenient for assay of fluconazole resistance and molecular epidemiological study of Candida albicans.

Antifungal Agents↗