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PubMedDate not supplied

Effects of cefepime, cefixime and ceftibuten on murine gut colonization by Candida albicans.

Crl:CD1(ICR) BR mice were fed chow containing Candida albicans or regular chow. Both groups were subsequently given either antibiotics or normal saline. Stool cultures were performed before, at the end of treatment and 1 week after treatment, to determine the effect on the stool yeast concentration. Candida-colonized mice treated with cefepime, cefixime or ceftibuten had higher (however not significantly) counts of the yeast in their stools than control Candida-fed mice treated with saline. A group of Candida-fed mice were treated with ceftriaxone, which is known to increase the yeast stool concentration significantly and served as positive control. Mice fed regular chow and treated with the study drugs or saline did not have any yeasts in their stools. Dissemination of Candida did not occur.

Animals↗
PubMedDate not supplied

Evaluation of polyene-azole antagonism in liquid cultures of Candida albicans using an automated turbidometric method.

BACKGROUND: A computerized machine, SPECTRAmax 340, was used to evaluate the recently reported phenomenon of antagonism of the polyene amphotericin B (AMB) in Candida albicans pre-exposed to the triazole fluconazole (FLZ). METHODS: We investigated growth inhibition by varying concentrations of AMB in seven isolates of C. albicans pre-exposed to FLZ (50 microg/ml) for 18 h. All isolates were obtained on sequential visits from human immunodeficiency virus-infected patients not treated with FLZ. RESULTS: Antagonism of AMB activity was observed in 5, 4, 2 and a single isolate for 0.5, 1, 2 and 3 microg/ml of the antifungal, respectively. In the majority of Candida isolates, antagonism was seen within a concentration range of 0.5-1.0 microg/ml AMB; 1 Candida strain (HK1-Sa) was resistant to 3 microg/ml AMB. Higher concentrations of AMB (>3 microg/ml) killed both the controls and FLZ-pre-exposed Candida cells. No significant differences were observed between the periods of antagonism observed for any of the sequential isolates or for any of the AMB concentrations or in the maxima of the growth curves obtained for all Candida isolates. CONCLUSION: We conclude that the SPECTRAmax system is a useful tool to evaluate in vitro pharmacodynamic interactions between antifungal regimens within a fluid culture system, and provides information that cannot be obtained using traditional plate assay systems.

Amphotericin B↗
PubMed2005

Complete inventory of ABC proteins in human pathogenic yeast, Candida albicans.

The recent completion of the sequencing project of the opportunistic human pathogenic yeast, Candida albicans (http://www.ncbi.nlm.nih.gov/), led us to analyze and classify its ATP-binding cassette (ABC) proteins, which constitute one of the largest superfamilies of proteins. Some of its members are multidrug transporters responsible for the commonly encountered problem of antifungal resistance. TBLASTN searches together with domain analysis identified 81 nucleotide-binding domains, which belong to 51 different putative open reading frames. Considering that each allelic pair represents a single ABC protein of the Candida genome, the total number of putative members of this superfamily is 28. Domain organization, sequence-based analysis and self-organizing map-based clustering led to the classification of Candida ABC proteins into 6 distinct subfamilies. Each subfamily from C. albicans has an equivalent in Saccharomyces cerevisiae suggesting a close evolutionary relationship between the two yeasts. Our searches also led to the identification of a new motif to each subfamily in Candida that could be used to identify sequences from the corresponding subfamily in other organisms. It is hoped that the inventory of Candida ABC transporters thus created will provide new insights into the role of ABC proteins in antifungal resistance as well as help in the functional characterization of the superfamily of these proteins.

ATP-Binding Cassette Transporters↗
PubMed1981

Monocyte-mediated serum-independent damage to hyphal and pseudohyphal forms of Candida albicans in vitro.

Human peripheral blood monocytes attached to Candida albicans hyphae in the absence of serum and damaged the hyphae without completely ingesting them. Attachment and damage was not augmented by the addition of serum. Damage to hyphae was quantitated by a previously developed metabolic assay that measured leukocyte-induced reduction in uptake of [(14)C]cytosine by the hyphae. Use of cells from patients with hereditary disorders of leukocyte function, chronic granulomatous disease, and myeloperoxidase deficiency indicated that myeloperoxidase-independent and nonoxidative mechanisms could sometimes damage hyphae where oxidative mechanisms were impaired. Damage to hyphae by normal monocytes was inhibited by concentrations of sodium azide and sodium cyanide that primarily affect myeloperoxidase activity, as well as by halide-free conditions, catalase, and putative antagonists of hypochlorous acid or singlet oxygen. Iodination of hyphae, a myeloperoxidase and hydrogen peroxide-dependent process of monocytes, was similarly inhibited by sodium azide, sodium cyanide, and catalase. Under anaerobic conditions, damage to hyphae was reduced by 64.0-68.4%. In contrast, inhibitors of potential nonoxidative antifungal mechanisms, iron salts to saturate iron chelators, and polyanionic amino acid polymers to neutralize cationic proteins did not block damage to hyphae by monocytes. Preparations rich in lysosomal granules from fractionated normal monocytes also did not damage hyphae. Overall, it appeared that oxidative mechanisms were most important for damage to hyphae by normal monocytes. Electron microscopy confirmed that Candida hyphae were damaged and probably killed by monocytes, but monocytes appeared to sustain significant damage in the process. In the absence of serum, monocyte cell membranes became closely approximated to Candida cell walls. It appeared that some Candida could escape this partial engulfment, as they were seen floating free with vesicular trilaminar membrane remnants covering hyphal surfaces. In general, monocytes appeared to be damaged by interactions with Candida hyphae more than neutrophils had been in previous studies.

Candida albicans↗
PubMedDate not supplied

Esterase activity in various Candida species.

The aim of the present study is to ascertain esterase activities of various species of Candida. A total of 125 strains isolated and identified by conventional methods were tested for esterase activity using the Tween 80 opacity test. Our results showed that 58 of 59 strains of Candida albicans, all of the Candida tropicalis strains (n = 38) and all of the Candida guilliermondii strains (n = 3) produced positive results, whereas the remaining Candida species did not. The Tween 80 opacity test is a useful method because it is simple, economical and easy to prepare and interpret.

Candida↗
PubMed2006

Candida-host interactions in HIV disease: relationships in oropharyngeal candidiasis.

Oropharyngeal candidiasis (OPC) caused by the commensal organism, Candida albicans, is the most common oral infection in HIV disease. Although cell-mediated immunity (CMI) by Th1-type CD4+ T-cells is considered the predominant host defense mechanism against OPC, other systemic or local immune mechanisms are critical when blood CD4+ T-cells are reduced below a protective threshold. For example, the Th cytokine profile in saliva may influence resistance or susceptibility to OPC. In OPC lesions, CD8+ T-cells become accumulated at the lamina propria-epithelium interface, suggesting some role for CD8+ T-cells against OPC. However, the absence of CD8+ T-cells close to Candida at the outer epithelium indicates that susceptibility to OPC involves a dysfunction in the CD8+ T-cells or in the micro-environment. Further evaluation of the buccal mucosa lesion showed that CD8 T-cell-associated cytokine and chemokine mRNA is increased compared with buccal mucosa from lesion-negative matched controls. The majority of CD8+ T-cells present possess the alphabeta T-cell receptor and several homing receptors (i.e., 4beta7, 4beta1, ebeta7). While several adhesion molecules are similar in OPC+ vs. OPC- persons, E-cadherin is reduced in the tissue of OPC+ persons. These results support evidence for a role for CD8+ T-cells against OPC, but suggest that a putative dysfunction in mucosal T-cell trafficking may be associated with susceptibility to infection. Similar levels of Candida-specific antibodies in persons with and without OPC confirmed a limited role for humoral immunity. Finally, oral epithelial cells inhibit the growth of Candida in vitro in a static rather than a cidal manner. Clinically, oral epithelial cell anti-Candida activity is reduced in HIV+ persons with OPC, compared with controls. The mechanism of action includes a strict requirement for cell contact by an acid-labile moiety on intact, but not necessarily live, epithelial cells, with no role for soluble factors. Taken together, host defense against OPC involves several levels of activity. The status and efficiency of local host defenses when blood CD4+ T-cells are not available appear to play a role in protection against or susceptibility to OPC.

AIDS-Related Opportunistic Infections↗
PubMed2004

Use of CHROMagar medium in the differentiation of Candida species: is it cost-effective in developing countries?

The opportunistic infection of humans with Candida is becoming more common. As several species of Candida are relatively insusceptible to the commonly used antifungal drugs, rapid identification of the species involved can facilitate effective treatment. CHROMagar Candida medium (CCM) is a commercial product designed to allow the rapid identification of Candida to species level. To explore the potential usefulness of CCM in a developing country, attempts were made to identify the Candida species in 107 Indian isolates (obtained, consecutively, from 90 clinical specimens, over a year-long period, in a tertiary-level teaching hospital), using CCM and more conventional methods in parallel. The most common species appeared to be C. tropicalis (representing 40% of the isolates), followed by C. albicans (28%) and C. glabrata (23%). Although use of CCM allowed the isolates from 84 (93.3%) of the clinical specimens to identified to species level within 48 h, it took at least 7 days to identify the yeasts in 90% of the specimens using the more conventional procedures. With the results of the conventional methods set as the 'gold standard', the use of CCM appeared to allow all of the C. albicans, C. tropicalis and C. krusei isolates and most (92%) of the C. glabrata to be correctly identified. The costs/isolate identified with the CCM were no more than those of the conventional methods. As many (67%) of the isolates examined were of potentially drug-resistant yeasts (C. tropicalis, C. glabrata or C. krusei), there is clearly a need to identify local isolates quickly, to prevent treatment with ineffective drugs. In terms of both performance and cost, CCM appears to be a good method to use.

Agar↗
PubMed2005

The trend of susceptibilities to amphotericin B and fluconazole of Candida species from 1999 to 2002 in Taiwan.

BACKGROUND: Candida species have various degrees of susceptibility to common antifungal drugs. The extent of resistance to amphotericin B and fluconazole of Candida glabrata isolates causing candidemia has been reported. Active surveillance may help us to monitor the trend of susceptibility to antifungal drugs and to determine if there is an emerging co-resistance to both drugs of Candida species, specifically, of C. glabrata in Taiwan. METHODS: The susceptibilities to amphotericin B and fluconazole of Candida species collected in 1999 and 2002 of the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) were determined by the microdilution method. RESULTS: The antifungal susceptibilities of 342 and 456 isolates collected from 11 hospitals participating in both TSARY 1999 and TSARY 2002, respectively, have been determined. The resistance rate to amphotericin B has increased from 0.3% in the TSARY1999 to 2.2% in the TSARY 2002. In contrast, the resistance rate to fluconazole has decreased from 8.8% to 2.2%. Nevertheless, significantly more C. glabrata isolates were not susceptible to fluconazole in the TSARY 2002 (47.4%) than that in the TSARY 1999 (20.8%). There were 9.8% and 11% of C. glabrata isolates having susceptible-dose dependent and resistant phenotype to fluconazole in the TSARY 1999, verse 45.3% and 2.1% in the TSARY 2002. CONCLUSION: There was an increase of resistance rate to amphotericin B in C. glabrata. On the other hand, although the resistance rate to fluconazole has decreased, almost half of C. glabrata isolates were not susceptible to this drug. Hence, continuous monitoring the emerging of co-resistance to both amphotericin B and fluconazole of Candida species, specifically, of C. glabrata, will be an important early-warning system.

Amphotericin B↗
PubMed2006

Limitations of caspofungin in the treatment of obstructive pyonephrosis due to Candida glabrata infection.

BACKGROUND: Caspofungin is a new antifungal agent with high-level activity against a number of Candida species including those that are resistant to azoles. Its good safety profile and low nephrotoxicity makes it an attractive drug to treat fungal infections in patients with compromised renal function. However, little is known about the clinical efficacy in the treatment of complicated urinary tract infections due to Candida species such as pyonephrosis. CASE PRESENTATION: We report a case of obstructive pyonephrosis due to an azole (fluconazole and itraconazole) resistant Candida glabrata strain that failed to respond to intravenous treatment with caspofungin. A sustained clinical and microbiological response was only achieved after percutaneous drainage and instillation of amphotericin B deoxycholate into the renal pelvis in combination with intravenous liposomal amphotericin B. CONCLUSION: This case demonstrates the limitation of intravenous antifungal agents such as caspofungin as the sole treatment of an obstructive upper urinary tract infection due to Candida species. In order to achieve long term sustained cure from an obstructive pyonephrosis, pus and fungal balls should be drained and an anti-fungal agent such as amphotericin B deoxycholate instilled locally. The pharmacokinetics and role of caspofungin in the treatment of complicated Candida urinary tract infection is reviewed.

Aged↗
PubMed2006

Effect of prolonged HAART on oral colonization with Candida and candidiasis.

BACKGROUND: Progressive cell-mediated immunodeficiency with decrease of CD4+ lymphocyte count to less than or equal to 200 cells/mm3 is a major risk factor for colonization with Candida species and development of candidiasis. Oropharyngeal candidiasis may occur in up to 90% of human immunodeficiency virus (HIV)-infected patients during the course of the disease. This study is to determine the effect of prolonged highly active antiretroviral therapy (HAART) on oropharyngeal colonization with Candida species and oral candidiasis. METHODS: A prospective, longitudinal follow-up study in HIV-infected patients receiving HAART. RESULTS: The mean CD4+ count increased from 232.5 to 316 cells/mm3 and the proportion of patients whose CD4+ count less than 200 cells/mm3 decreased from 50.0% to 28.9% (p = 0.0003) in patients receiving HAART for at least 2 years. The prevalence of oral candidiasis decreased from 10.6% to 2.1% (p = 0.004). The decrease in Candida colonization was less impressive, falling from 57.8% to 46.5 % (p = 0.06). Of the 142 patients enrolled in at least two surveys, 48 (33.8%) remained colonized with Candida and 42 (29.6%) remained negative. In the remaining 52 patients, 34 switched from culture positive to negative, and an increase in CD4+ lymphocytes was noted in 91.2% of them. Among the 18 patients who switched from culture negative to positive, 61.1% also demonstrated an increase in CD4+ lymphocyte count (p = 0.01). CONCLUSION: These findings indicate that HAART is highly effective in decreasing oral candidiasis in association with a rise in CD4+ lymphocyte counts, but only marginally effective in eliminating Candida from the oropharynx.

AIDS-Related Opportunistic Infections↗
PubMed1988

Human and rabbit newborn lung macrophages have reduced anti-Candida activity.

Bronchoalveolar macrophages (BAM) protect the adult lung from low level microbial contamination. The antimicrobial activity of human newborn BAM is unknown. BAM were isolated from effluents of suctioned, intubated newborns and from bronchoalveolar lavage of healthy, nonsmoking adult volunteers. An in vitro cytologic slide assay was developed and used to ascertain: 1) inhibition of intracellular filamentation of Candida albicans (active yeast growth) and 2) killing + digestion of ingested C. albicans. The ability to restrict intracellular yeast filamentation was markedly different for human newborn versus adult BAM. Adult BAM were five times more effective in restricting intracellular filamentation of Candida compared to newborn cells (p less than 0.01). Nonfilamented ingested yeast were also handled differently by newborn and adult macrophages. Nonfilamented yeast were killed and digested by adult BAM at a rate that was 2.5 times above that noted in neonatal lung macrophages (p less than 0.005). However, no differences were found in the total number of killed + digested Candida within human newborn and adult BAM [adult = 32.4 +/- 10.5% (n = 5), newborn less than 1200 g = 39.6 +/- 16.8% (n = 8), and newborn greater than 1200 g = 30.2 +/- 11.1% (n = 16), mean +/- S.D.]. Neonatal BAM were able to destroy C. albicans at a level equivalent to adult cells because these newborn phagocytes allowed intracellular Candida to enter a state of active growth, thereby rendering the yeast more susceptible to killing and digestion. The anti-Candida activity noted in lung macrophages recovered from normal 1-day-old and adult rabbits was similar to that seen in human BAM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Shifting patterns in the epidemiology of nosocomial Candida infections.

The incidence of candidemia--a common and potentially fatal nosocomial infection--has risen dramatically, and this increase has been accompanied by a shift in the infecting pathogen away from Candida albicans to treatment-resistant non-albicans species. Prophylactic azole antifungals, such as fluconazole, may play an important role not only in the management of candidemia but also in the proliferation of hard-to-treat Candida species. In a variety of acute nosocomial settings, IV fluconazole, 400 mg/d, has reduced Candida colonization and infection. A growing body of evidence supports the still controversial contention that the increasing use of azole antifungals is at least partially responsible for the proliferation of treatment-resistant, non-albicans isolates, especially Candida glabrata. Thus, selecting the most appropriate candidates for prophylactic antifungal intervention--ie, those with the highest risk for candidemia--may be indispensable, not only in preventing candidemia, but also in reducing antifungal overuse, which may contribute to the emergence of treatment-resistant Candida isolates.

Antifungal Agents↗
PubMed2004

Evaluation of biochemical and serological methods to identify and clustering yeast cells of oral Candida species by CHROMagar test, SDS-PAGE and ELISA.

The purpose of this work was to evaluate biochemical and serological methods to characterize and identify Candida species from the oral cavity. The strains used were five Candida species previously identified: C. albicans, C. guilliermondii, C. parapsilosis, C. krusei, C. tropicalis, and Kluyveromyces marxianus, as a negative control. The analyses were conducted through the SDS-PAGE associated with statistical analysis using software, chromogenic medium, and CHROMagar Candida (CA), as a differential medium for the isolation and presumptive identification of clinically important yeasts and an enzyme-linked immunoabsorbent assay (ELISA), using antisera produced against antigens from two C. albicans strains. This method enabled the screening of the three Candida species: C. albicans, C. tropicalis, and C. krusei, with 100% of specificity. The ELISA using purified immunoglobulin G showed a high level of cross-reaction against protein extracts of Candida species. The SDS-PAGE method allowed the clustering of species-specific isolates using the Simple Matching coefficient, S(SM) = 1.0. The protein profile analysis by SDS-PAGE increases what is known about the taxonomic relationships among oral yeasts. This methodology showed good reproducibility and allows collection of useful information for numerical analysis on information relevant to clinical application, and epidemiological and systematical studies.

Animals↗
PubMed2004

In vitro antifungal susceptibility of Candida spp. isolates from patients with chronic periodontitis and from control patients.

Superinfection by Candida can be refractory to conventional periodontal treatments in specific situations, such as in immunocompromised patients. In these cases, the systemic therapy with antifungal drugs could be indicated. The aim of this study was to analyse antifungal susceptibility of Candida spp. strains isolated from chronic periodontitis patients and from control individuals. A total of 39 C. albicans isolates, 9 C. tropicalis, 2 C. glabrata and 5 Candida spp. from control individuals and 30 C. albicans, 3 C. tropicalis and 2 C. glabrata from periodontitis patients were tested. In the control group, 1 isolate of C. glabrata was resistant to ketoconazole and 1 Candida spp. was resistant to amphotericin B, ketoconazole and miconazole. Among the isolates of periodontitis group, 1 (3.33%) C. albicans isolate was resistant to flucytosine and ketoconazole. According to the obtained results, it could be concluded that fluconazole was the most effective drug against the several Candida species studied. There were not expressive differences in the susceptibility of isolates from periodontitis patients or from control individuals.

Adult↗
PubMed2005

Systemic fungal infections caused by Candida species: epidemiology, infection process and virulence attributes.

Candida species, in particular C. albicans, represent a major threat to immunocompromised patients. Able to exist as a commensal on mucosal surfaces of healthy individuals, these opportunistic fungi frequently cause superficial infections of mucosae and skin. Furthermore, in hospital settings, Candida species may cause life-threatening invasive infections in a growing population of vulnerable patients. In fact, candidaemia is associated with the highest crude mortality of all bloodstream infections. Candida cells may enter the bloodstream by direct penetration from epithelial tissues, due to damage of barriers in the body caused by surgery, polytrauma or drug treatment, or may spread from biofilms produced on medical devices. From the bloodstream, cells may infect almost all organs but appear to prefer certain organs depending upon the route of infection. The exact mechanisms by which Candida cells survive the challenge of the blood environment and escape from the bloodstream to cause deep-seated infections have not yet been elucidated, but various investigations are reviewed. It is clear, however, that Candida must have particular attributes which enable the organism to survive and grow within the environment of healthy individuals and to invade tissues in the immunocompromised host. Most studies have focussed on C. albicans and this review will therefore summarise work on the various known virulence factors and methods used to identify further virulence attributes of this fungus.

Candida↗
PubMed1990

[Change of number of oral Candida species by tongue brushing].

The purpose of this study was to investigate the influence of tongue brushing on the change of oral Candida species. Among the tongue brushing programs for 50 days, 5 subjects wearing dentures were measured the number of Candida species at tongue, denture and denture bearing mucosa and in oral rinsing. The following results were obtained. 1. After the tongue brushing program, the number of Candida species at tongue and in oral rinsing decreased significantly. 2. The tongue brushing with denture plaque control decreased in number of Candida species at denture more effectively than without denture plaque control. 3. The number of Candida species at denture bearing mucosa decreased by tongue brushing. 4. It seemed that the tongue brushing was effective to prevent denture stomatitis caused by denture plaque.

Aged↗
PubMed2002

A phylogenetic study of ubiquinone-7 species of the genus Candida based on 18S ribosomal DNA sequence divergence.

To clarify phylogenetic relationships among ubiquinone 7 (Q7)-forming species of the genus Candida, we analyzed the nearly complete sequences of 18S ribosomal RNA genes (18S rDNAs) from fifty strains (including 46 type strains) of Candida species, and from 8 type strains of species/varieties of the genera Issatchenkia, Pichia and Saturnispora. Q7-forming Candida species were divided into three major groups (Group I, II, and III) and were phylogenetically distant from a group that includes the type species of the genus Candida. Group I included four clusters with basal branches that were weakly supported. The first cluster comprised C. vartiovaarae, C. maritima, C. utilis, C. freyschussii, C. odintsovae, C. melinii, C. quercuum, Williopsis saturnus var. saturnus, and W. mucosa. The second cluster comprised C. norvegica, C. montana, C. stellimalicola, C. solani, C. berthetii, and C. dendrica. Williopsis pratensis, W. californica, Pichia opuntiae and 2 related species, P. amethionina (two varieties), and P. caribaea were also included in this cluster. The third cluster comprised C. pelliculosa (anamorph of P. anomala), C. nitrativorans, and C. silvicultrix. The fourth cluster comprised C. wickerhamii and C. peltata, which were placed in the P. holstii - C. ernobii clade with Q8-containing species. Group II comprised C. pignaliae, C. nemodendra, C. methanolovescens, C. maris, C. sonorensis, C. pini, C. llanquihuensis, C. cariosilignicola, C. ovalis, C. succiphila (including its two synonyms), C. methanosorbosa, C. nitratophila, C. nanaspora, C. boidinii (including its two synonyms), W. salicorniae, and P. methanolica. Group III was composed of four clusters with strong bootstrap support. The first cluster comprised C. valida (anamorph of P. membranifaciens), C. ethanolica, C. pseudolambica, C. citrea, C. inconspicua, C. norvegensis, C. rugopelliculosa, and C. lambica. Three species and two varieties of the genus Issatchenkia were also included in this cluster. The second cluster comprised C. diversa, C. silvae, 4 Saturnispora species, and P. besseyi. The third comprised C. sorboxylosa, and the fourth comprised C. vini. Based on this 18S rDNA sequence analysis, it is evident that Q7-forming Candida species and the genera Pichia and Williopsis are polyphyletic. The genus Issatchenkia is suggested to be congeneric with the genus Pichia. The genus Saturnispora is phylogenetically definable.

Ascomycota↗
PubMed1989

The diagnosis of candida vaginitis in general practice.

In a multi-practice study, 29 general practitioners registered 361 women with increased vaginal discharge, malodour, or pruritus, and 229 women without vaginal complants. A wet-smear was examined for Candida by the general practitioner. Culture for Candida was performed in the general practitioner's laboratory, and at a microbiological laboratory. Candida was found by microscopy or culture in 140 (39%) women with vaginal symptoms, compared with 51 (22%) without vaginal complaints (p less than 0.001). In 34 women with symptoms (24%) Candida was found by wet-smear microscopy, in 98 (76%) by microscopy or culture in the general practitioner's laboratory, and in 126 (90%) by microscopy or culture at the microbiological laboratory. No relation was found between the number of Candida isolated and the presence of vaginal symptoms (p greater than 0.05). The sensitivity of microscopy was low compared with previous studies and underlines the need for multi-practice studies in the evaluation of diagnostic procedures. Vagicult is recommended for general practice, but problems exist in the interpretation of a positive culture result.

Adult↗