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PubMed1999

National epidemiology of mycoses survey (NEMIS): variations in rates of bloodstream infections due to Candida species in seven surgical intensive care units and six neonatal intensive care units.

Candida species are the fourth most frequent cause of nosocomial bloodstream infections, and 25%-50% occur in critical care units. During an 18-month prospective study period, all patients admitted for > or = 72 hours to the surgical (SICUs) or neonatal intensive care units (NICUs) at each of the participant institutions were followed daily. Among 4,276 patients admitted to the seven SICUs in six centers, there were 42 nosocomial bloodstream infections due to Candida species (9.8/1,000 admissions; 0.99/1,000 patient-days). Of 2,847 babies admitted to the six NICUs, 35 acquired a nosocomial bloodstream infection due to Candida species (12.3/1,000 admissions; 0.64/1,000 patient-days). The following were the most commonly isolated Candida species causing bloodstream infections in the SICU: Candida albicans, 48%; Candida glabrata, 24%; Candida tropicalis, 19%; Candida parapsilosis, 7%; Candida species not otherwise specified, 2%. In the NICU the distribution was as follows: C. albicans, 63%; C. glabrata, 6%; C. parapsilosis, 29%; other, 3%. Of the patients, 30%-50% developed incidental stool colonization, 23% of SICU patients developed incidental urine colonization, and one-third of SICU health care workers' hands were positive for Candida species.

Candidiasis↗
PubMed2001

[Role of neutrophils in acute lung injury induced by Candida sepsis].

To evaluate the role of inflammatory cells in acute lung injury induced by Candida sepsis, we investigated the time course of cell counts in bronchoalveolar lavage (BAL) fluid, the lung wet-to-dry weight (W/D) ratio and the CFU of Candida after a Candida infection. Male BALB/c mice were injected intravenously with 107 CFU of Candida albicans. They were sacrificed by exsanguination 0, 6, 12, 18, and 24 h after infection. The lung W/D ratio was determined in order to assess the severity of pulmonary edema. BAL was performed 3 times with 0.5 ml of sterile saline. The lung W/D ratio increased significantly 24 h after the injection of Candida, and the neutrophil counts in the BAL fluid increased significantly 12, 18, and 24 h after Candida injection. To assess the effect of neutrophils on Candida-induced acute lung injury, we investigated that of neutrocytosis and neutropenia on cell counts in BAL fluid, of the W/D ratio, and of the CFU of Candida in the lung 24 h after infection. We created neutrocytotic mice using G-CSF, and neutropenic mice with cyclophosphamide. Peripheral neutrophil counts decreased significantly in cyclophosphamide-treated mice, and increased significantly in G-CSF-treated mice. The lung W/D ratio increased significantly in cyclophosphamide-treated mice. Neutrophil counts in BAL fluid increased significantly in G-CSF-treated mice, and decreased significantly in cyclophosphamide-treated mice. The CFU of Candida in the lung decreased significantly in G-CSF-treated mice, and increased significantly in cyclophosphamide-treated mice. We concluded that neutrophils play a protective role in Candida albicans-induced acute lung injury.

Acute Disease↗
PubMed2001

Effect of contraceptives on the prevalence of vaginal colonization with Candida species in Edo State, Nigeria.

High vaginal swabs (HVS) obtained from 500 volunteers in Edo State, Nigeria which comprised 394 contraceptive users and 106 non-contraceptive users were screened for the prevalence of Candida species using standard procedures. Results revealed the isolation of Candida species in 246 of volunteers. These included Candida albicans 174 (38.4%), Candida pseudotropicalis 20 (4%), Candida stellatoidea 15 (3%), Candida krusei nine (1.8%), Candida guilliermondii 12 (2.4%), Candida tropicalis 11 (2.2%) and Candida glabrata five (1%). Of the 394 contraceptive users, 203 (51.5%) had Candida species isolated from them compared to 43 (40.6%) from 106 non-contraceptive users. There was significant relationship (P<0.001) between the type of contraceptive used and the prevalence of vaginal colonization. Age and marital status of the volunteers sampled had significant relationship (P<0.001) with the prevalence of vaginal colonization. Results have revealed an association between use of contraceptive and the prevalence of vaginal colonization in our environment.

Journal Article↗
PubMed1997

[Oral contraceptive use and vaginal candida colonization].

Fungal vaginal infections/colonisations can be divided into a symptomatic vaginal candidiasis and an asymptomatic vaginal Candida-carriage. The latter seems to be a predisposing factor for the development of a symptomatic vaginal candidiasis. The fungal organism isolated most frequently is Candida albicans, followed by Candida glabrata, which was previously also known as Torulopsis glabrata. To a lower extend, other Candida species such as Candida tropicalis and Candida krusei can be prevalent in the vulvovaginal region. Predisposing factors for vaginal candidiasis are gravidity, diabetes mellitus or a therapy with immunosuppressive agents. Also gestagenes showed to be a pre-disposing factor for vaginal candidiasis. Divergent results concerning the predisposition to vaginal candidiasis or colonisation due to oral contraception have so far been reported. Therefore we performed a study with two healthy collectives of female volunteers (n = 2 x 60) which were different concerning the taking of oral contraceptives. Overall, in 17% of the subjects (20/120) yeast could be cultured out of the vaginal secretions. There was no evidence for a higher rate of Candida-colonisation in subjects taking oral contraceptives. Further, there was no evidence for a relationship between the length of the taking of oral contraceptives and the rate of vaginal yeast-carriage. Also the type of oral contraceptive (combination or sequential contraceptive) had no influence on the frequency of Candida-carriage. Candida albicans was the most prevalent yeast (16/20), followed by Candida glabrata (4/20).

Adult↗
PubMed1991

In vitro comparison of cilofungin alone and in combination with other antifungal agents against clinical isolates of Candida species.

Cilofungin, a lipopeptide antifungal agent, was tested for in vitro activity alone and in combination with ketoconazole, itraconazole, flucytosine and amphotericin B against 102 clinical isolates of Candida species. At 48 hours all isolates of Candida albicans, Candida tropicalis, Candida paratropicalis and Candida glabrata were inhibited by less than or equal to 5 meg/ml of cilofungin. In contrast, the MIC90 for Candida krusei was 10 mcg/ml and for Candida parapsilosis greater than 40 mcg/ml. The interaction of combinations of cilofungin with amphotericin B, itraconazole, ketoconazole and flucytosine was additive or indifferent at 48 hours for 100%, 88%, 78% and 70% of all Candida species isolates, respectively. Overall, cilofungin demonstrated good activity in vitro against most Candida species isolates.

Amphotericin B↗
PubMed1977

Experimental hematogenous endophthalmitis due to Candida: species variation in ocular pathogenicity.

The ocular pathogenicity of species of Candida other than albicans was studied in the rabbit model of hematogenous candida endophthalmitis by injection of 10(5)-10(8) colony-forming units of Candida krusei, Candida parapsilosis, Candida guilliermondii, Candida tropicalis, Candida stellateoidea, and Candida albicans (control). At one and three weeks after infection, rabbits were examined by indirect ophthalmoscopy and were sacrificed for culture of eyes and kidneys. With an inoculum of 10(8) organisms, C. tropicalis and C. stellatoidea infected the kidneys but only occasionally infected the chorioretina and never infected the vitreous. Organisms were cultured only rarely from the kidneys of rabbits infected with C. krusei, C. guilliermondii, and C. parapsilosis; these species were never isolated from eyes. The C. albicans control consistently infected the kidney, chorioretina, and vitreous; approximately equal numbers of C. albicans were isolated from these organs. These data suggest a relative resistance of ocular tissues to hematogenous candida infections with species other than C. albicans.

Animals↗
PubMed2006

The carriage of Candida species on the dorsal surface of the tongue: the correlation with the dental, periodontal and prosthetic status in elderly subjects.

OBJECTIVES: To screen the carriage status of Candida species, especially Candida albicans and its genotype in an epidemiological survey and to investigate its correlation with the dental, periodontal and prosthetic status of healthy elderly subjects. MATERIALS AND METHODS: Microbiological samples were collected from the dorsum of the tongue of 366 subjects, aged 75, and cultured on CHROMagar medium. The carriage status of Candida spp. and the distribution of C. albicans genotypes by a polymerase chain reaction (PCR) method were analysed and compared with the dental, periodontal and prosthetic status of the subjects. RESULTS: A high carriage rate (68.6%) of Candida spp. and the predominant species of C. albicans (72.1%) were found in this study. The prevalence, density and multi-species of Candida spp. were significantly related to the presence of a dental prosthesis. In C. albicans, genotype A predominated (56.4%) and genotype D showed a higher prevalence (12.5%) than previous reports. When comparing Candida spp. carriage with the oral status, significant positive correlations were found with the presence of any dental prosthesis, missing teeth, the number of retained roots and the percentage of sites showing bleeding on probing (BOP), while significant negative correlations were found with the number of teeth present, sound and filled teeth. CONCLUSIONS: Candida carriage on the dorsum of the tongue in healthy elderly is significantly associated with the dental, periodontal and prosthetic status, especially the presence of a dental prosthesis. As the complexity of the prosthesis being worn increased, the relative risk of Candida carriage and the numbers and multi-species of Candida increased accordingly.

Aged↗
PubMed1987

Molecular probe for identification of medically important Candida species and Torulopsis glabrata.

A cloned DNA fragment from Candida albicans containing the gene for the protein actin was used to probe the molecular structure of the actin gene of several medically important yeasts (C. albicans, Candida stellatoidea, Candida tropicalis, Candida pseudotropicalis, Candida krusei, Candida parapsilosis, Candida guilliermondii, and Torulopsis glabrata). Whole-cell DNA from each species was digested with restriction endonucleases, electrophoresed on agarose gels, and transferred to nitrocellulose. Radioactively labeled C. albicans actin gene was hybridized to the DNA fragments on the nitrocellulose. The C. albicans probe produced a strong signal with all of the Candida DNAs tested, indicating considerable conservation of this gene. In addition, the actin genes of all of the species tested were found to have no internal EcoRI or SalI restriction sites. With the exception of C. guilliermondii, all of the species tested had a single internal HindIII recognition site. However, the location of flanking restriction sites was found to be species specific. For all of the enzymes tested, the locations of the flanking restriction sites in C. albicans and C. stellatoidea were identical; all of the other strains yielded fragments clearly distinct from one another. These differences provide a molecular tool for the differentiation of medically important Candida species.

Actins↗
PubMed2002

Biofilm production by isolates of Candida species recovered from nonneutropenic patients: comparison of bloodstream isolates with isolates from other sources.

Biofilm production has been implicated as a potential virulence factor of some Candida species responsible for catheter-related fungemia in patients receiving parenteral nutrition. We therefore compared clinical bloodstream isolates representing seven different Candida species to each other and to those from other anatomical sites for the capacity to form biofilms in glucose-containing medium. Potential associations between the capacity to form biofilms and the clinical characteristics of fungemia were also analyzed. Isolates included the following from nonneutropenic patients: 101 bloodstream isolates (35 C. parapsilosis, 30 C. albicans, 18 C. tropicalis, 8 C. glabrata, and 10 other Candida species isolates) and 259 clinical isolates from other body sites (116 C. albicans, 53 C. glabrata, 43 C. tropicalis, 17 C. parapsilosis, and 30 other Candida species isolates). Organisms were grown in Sabouraud dextrose broth (SDB) containing a final concentration of 8% glucose to induce biofilm formation, as published previously. Biofilm production was determined by both visual and spectrophotometric methods. In this medium, biofilm production by C. albicans isolates was significantly less frequent (8%) than that by non-C. albicans Candida species (61%; P < 0.0001). The overall proportion of non-C. albicans Candida species isolates from the blood that produced biofilms was significantly higher than that of non-C. albicans Candida isolates obtained from other sites (79% versus 52%; P = 0.0001). Bloodstream isolates of C. parapsilosis alone were significantly more likely to be biofilm positive than were C. parapsilosis isolates from other sites (86% versus 47%; P = 0.0032). Non-C. albicans Candida species, including C. parapsilosis, were more likely to be biofilm positive if isolates were derived from patients whose candidemia was central venous catheter (CVC) related (95%; P < 0.0001) and was associated with the use of total parenteral nutrition (TPN) (94%; P < 0.005). These data suggest that the capacity of Candida species isolates to produce biofilms in vitro in glucose-containing SDB may be a reflection of the pathogenic potential of these isolates to cause CVC-related fungemia in patients receiving TPN.

Biofilms↗
PubMed2006

Triazole cross-resistance among Candida spp.: case report, occurrence among bloodstream isolates, and implications for antifungal therapy.

Candida spp. are common causes of bloodstream infections among hospitalized patients. Fluconazole (FLC) remains a first-line therapy for candidemia; and voriconazole (VRC), an expanded-spectrum triazole, was recently approved for the treatment of candidemia in nonneutropenic patients. In vitro studies have suggested that VRC has potent activity against Candida spp. with reduced susceptibilities to FLC. We present a case report of invasive candidiasis and candidemia due to a Candida glabrata isolate that developed resistance to all currently available triazole antifungals after a course of FLC treatment. This case prompted us to determine the frequency of cross-resistance among bloodstream Candida isolates collected during a recent 12-month period at a large, academic medical center. FLC MICs were determined for 125 of 153 isolates (81.7%). Thirty of 125 isolates (24%) were resistant or showed reduced susceptibilites to FLC (MICs >/= 16 microg/ml). When 28 of these 30 isolates were tested for their VRC susceptibilities, 9 (32%) had MICs that were >/=2 microg/ml. Five of these nine isolates were C. glabrata, two isolates were Candida tropicalis, one isolate was Candida albicans, and one isolate was Candida parapsilosis. All five Candida krusei isolates tested had VRC MICs </=0.5 microg/ml. These data have prompted the introduction of reflexive FLC susceptibility testing of first bloodstream Candida isolates at our institution. The case report and our data also suggest that VRC should be avoided as initial therapy in unstable patients with invasive candidiasis, particularly in the setting of prior azole exposure. Studies are needed to define the clinical significance of in vitro resistance to the newer antifungal agents.

Antifungal Agents↗
PubMed2005

In vitro susceptibility of oral Candida to seven antifungal agents.

The in vitro susceptibility of 618 Candida isolates to fluconazole, itraconazole, voriconazole, ketoconazole, miconazole, amphotericin B, and nystatin was determined. The isolates were obtained from 559 patients who had attended the UK dental hospital departments in Cardiff, Belfast, Glasgow or London. Antifungal susceptibility was assessed using a broth microdilution method following the National Committee for Clinical Laboratory Standards (NCCLS) M27-A guidelines. The majority of the test strains were C. albicans (n = 521) with few of these being resistant to fluconazole (0.3%). A low incidence of fluconazole resistance (0-6.8%) was similarly evident with all non albicans species (Candida glabrata, 5 of 59 resistant; Candida krusei, 0 of 7 resistant; Candida tropicalis, 0 of 13 resistant; Candida parapsilosis, 0 of 12 resistant; other Candida species, 0 of 6 resistant). Voriconazole, ketoconazole, and miconazole also revealed high activity against both C. albicans and non albicans isolates, and 23.7% of C. glabrata isolates were found to be resistant to itraconazole. There was little difference in the antifungal susceptibilities of Candida isolated from patients who had a history of previous antifungal therapy compared with those who had not received antifungal treatment. In summary, this surveillance study of antifungal susceptibility of oral candidal isolates in the UK, through the collaboration of four dental hospitals, demonstrates that oral Candida species have a high level of susceptibilities to a range of antifungal agents.

Amphotericin B↗
PubMed1997

Use of specialised isolation media for recognition and identification of Candida dubliniensis isolates from HIV-infected patients.

During a study of oral rinses of 130 HIV-infected individuals, both typical and atypical Candida albicans colonies were isolated from ten patients on a yeast differential medium. Typical Candida albicans colonies were light green; atypical colonies were dark green. Both types of colonies were germ tube-positive and produced chlamydospores. However, DNA fingerprinting of the atypical isolates with the Ca3 Candida albicans-specific probe showed that they belonged to the recently described species Candida dubliniensis. Candida dubliniensis colonies could also be differentiated from Candida albicans colonies on isolation plates by the absence of fluorescence of colonies on methyl blue-Sabouraud agar under Wood's light. Among other phenotypic characteristics, only the absence of intracellular beta-glucosidase activity reliably distinguished Candida albicans from Candida dubliniensis. Candida dubliniensis may be underreported in clinical samples because most currently used isolation and identification methods fail to recognize this yeast.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Incidence and significance of candida antigen in low-risk and high-risk patient populations.

A latex agglutination test which detects candida antigen in patients with disseminated infection was used to screen 328 patients. Of these patients 100 had renal failure but no signs or symptoms of candida infection, and 100 had high rheumatoid factor titers but also no signs or symptoms of candida infection. The remaining 128 patients were considered at high risk of developing systemic candida infection. Sequential titers were also determined in a number of these patients. The incidence of candida antigen titers greater than or equal to 1:4 in the low-risk population was 3% as compared to 53% in the high-risk group. None of the patients with positive rheumatoid factor titers had candida antigen titers greater than or equal to 1:2, however 13% had nonspecific agglutination at titers greater than 1:2. The incidence of nonspecific agglutination increased with increasing rheumatoid factor titers. In general the candida antigen titers correlated well with clinical findings and with the course of infection in those patients in whom sequential candida antigen titers were determined. This latex test thus appears to be a useful adjunct procedure for the diagnosis of serious candida infections.

Antigens, Fungal↗
PubMed2006

Candida-induced oral epithelial cell responses.

OBJECTIVE: Oropharyngeal candidiasis (OPC), caused by Candida albicans, is the most common oral infection in HIV(+) persons. Oral epithelial cells are considered important for innate host defense against OPC with production of cytokines in response to C. albicans and the ability to inhibit Candida growth in vitro. The purpose of this study was to determine if Candida similarly induces cytokines by oral epithelial cells from HIV(+) persons, including those with OPC, as well as to determine if cytokines can influence the oral epithelial cell anti-Candida activity. METHODS: Supernatants from oral epithelial cells from HIV(+) persons with and without OPC cultured with Candida were evaluated for cytokines by ELISA, or cytokines were added to the standard growth inhibition assay using epithelial cells from HIV(-) persons. RESULTS: Results showed low Candida-induced epithelial cell cytokine production from HIV(+) persons, but with some elevated proinflammatory cytokines (TNF-alpha, IL-6) in those with OPC compared to those without OPC. The addition of specific proinflammatory or Th cytokines had no effect on oral epithelial cell anti-Candida activity in healthy HIV(-) persons. CONCLUSION: These results suggest that oral epithelial cells from HIV(+) persons can contribute at some level to the oral cytokine milieu in response to Candida during OPC, but that cytokines do not appear to influence oral epithelial cell anti-Candida activity.

AIDS-Related Opportunistic Infections↗
PubMed2002

In vivo pathogenicity of eight medically relevant Candida species in an animal model.

BACKGROUND: The relative pathogenicity of eight medically important Candida species was investigated in a mouse model. MATERIALS AND METHODS: Seventeen isolates were included; two isolates of Candida albicans, Candida glabrata, Candida tropicalis, Candida lusitaniae, Candida parapsilosis, Candida kefyr and Candida guilliermondii and three Candida krusei isolates. Mice in groups of three or four were inoculated with 10(5) and 10(7) CFU, respectively. On days 2 and 7 kidneys were removed, weighed and CFU/g kidney determined by the spot technique. RESULTS: Mortality was only observed in mice inoculated with C. albicans and C. tropicalis. Inoculated with 10(7) CFU C. tropicalis, C. glabrata, C. kefyr, C. lusitaniae, C. parapsilosis, C. krusei and C. guilliermondii the median log CFU/g kidney was significantly different: 6.0, 6.0, 6.4, 7.0, 3.7, < 2 and < 2 respectively (p < 0.0001). Eye infection and histological changes of kidneys were examined for C. albicans, C. tropicalis, C. glabrata and C. krusei-infected mice. Weight loss, kidney weight, inflammation and infection and number of eyes infected decreased with the pathogenicity of the four species. CONCLUSION: The virulence was highly different, illustrated by a 7-log difference in CFU/g kidney, a span of 0-100% mortality and histological changes in kidneys ranging from discrete to serious. The species could be divided into three groups with decreasing virulence: 1) C. albicans and C. tropicalis, 2) C. glabrata, C. kefyr and C. lusitaniae and 3) C. parapsilosis, C. krusei and C. guilliermondii. To our knowledge this is the first study with a simultaneous comparison of all eight species in an immunocompetent animal model.

Animals↗
PubMed2005

Prevalence of Candida species in Turkish children: relationship between dietary intake and carriage.

In this study, the prevalence and intensity of Candida species were evaluated in 300 healthy Turkish children aged between 0 and 12 years. The candidal carriage in 26 children who were fed only with breast milk and 38 children who were fed with both breast milk and bottle milk or other fluids was also examined. Oral samples cultured for fungal growth and Candida species were identified using germ tube test, chlamydospore formation test and API 20C AUX system. The results demonstrated that the prevalence of oral candidal carriage in 300 healthy children was 26.3%. Candida albicans was the most frequently isolated yeast (84.8% of the isolates). The other yeasts were identified as Candida parapsilosis, Candida krusei, Candida kefyr, Candida famata, and Candida tropicalis. It was also observed that the frequency of carriage varied as a function of age. The prevalence of carriage in children who were fed with both breast milk and bottle milk or other fluids was 18.5%, while in children fed only with breast milk was 0%. This finding supports previously reported observations that there may be intrinsic differences in oral carriage of Candida species between different ages and populations and type of dietary intake may affect frequency of carriage.

Age Factors↗
PubMed2005

Rapid identification of Candida species by FT-IR microspectroscopy.

Due to the continuous increase of human candidiasis and the great diversity of yeasts of the Candida genera, it is indispensable to identify this yeast as early as possible. Early identification enables an early diagnostic and patient-adapted anti-fungal therapy, thus reducing morbidity and mortality related to these infections. In view of this, we have in this study investigated microcolonies using a method based on Fourier transform-infrared microspectroscopy (FTIRM) for a rapid and early identification of the most frequent Candida species encountered in human pathology. FTIR spectroscopy is a whole-cell "fingerprinting" method by which microorganisms can be identified. By exploiting the huge discriminating capacity of this technique, we identified 6 species (Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei, and Candida kefyr) from a collection of 57 clinical strains of Candida, isolated from hospitalised patients. Data obtained on 10- to 18-h-old microcolonies were compared to cultures of 24 h. Our results clearly show the efficiency and the robustness of FTIR (micro)spectroscopy in identifying species with a classification rate of 100% for both microcolonies and 24-h cultures. FTIR microspectroscopy is thus a promising clinical approach, because compared to conventional and molecular techniques, it is time and money saving, has great identification and discriminating potentials, and is amenable to an automated high-throughput routine system.

Candida↗
PubMed2001

Increase of Candida cell virulence by anticancer drugs and irradiation.

The influence of anticancer drugs and irradiation on Candida cell proliferation, adherence to HeLa cells and susceptibility to antifungal drugs (amphotericin B and miconazole) and neutrophils were examined using two Candida albicans strains. After treatment with 5-fluorouracil (25 microg/ml to 250 microg/ml), cis-diammine-dichloroplatinum (10 microg/ml to 100 microg/ml), peplomycin (0.5 microg/ml to 5 microg/ml) or 137Cs (20 Gy to 40 Gy) for 3 days or more, surviving Candida cells proliferated more rapidly than did untreated control cells. Anticancer agent-pretreated Candida cells revealed an increased adhesion to HeLa cells corresponding to an increase of binding to the lectins. The concentration of half limited colony formation (IC50) of amphotericin B and miconazole was increased to near two-fold that of the control by pretreatment of Candida cells with the anticancer agents, except peplomycin, which only weakly increased IC50. In addition, the enolase and Candida acid proteinase activities in the culture supernatants were increased by pretreatment with the drugs and irradiation. Correspondingly, surviving Candida cells after these treatments were resistant to neutrophils, with a reduction to half of the killing. These results indicate that anti-cancer drugs and irradiation potentiate the virulence of Candida cells, or they eliminate Candida cells with low virulence, thereby enhancing the risk of oral and systemic candidiasis.

Amphotericin B↗