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PubMed1999

Adherence of Candida albicans to bladder mucosa: development and application of a tissue explant assay.

In order to study the interactions between Candida species and uroepithelial tissue, a tissue explant assay was developed using bladder mucosa harvested from New Zealand white rabbits. Blastoconidia of Candida albicans, Candida tropicalis and Candida glabrata attached to the uroepithelial tissue in similar quantities. However, there was significantly more adherence to the uroepithelium by pre-germinated C. albicans compared with C. albicans blastoconidia. Furthermore, the amount of uroepithelial tissue injury was directly related to the length of exposure of the tissue to Candida. Thus, this tissue explant assay may provide a useful method for investigating properties related to fungal adherence to transitional uroepithelium and organism-mediated tissue injury.

Animals↗
PubMed2002

Diagnosis of systemic Candida infections in patients of the intensive care unit. Significance of serum antigens and antibodies.

The combined detection of Candida antigen and antibody for the determination of systemic Candida infections (SCI) was investigated. One hundred and four patients from the intensive care unit (ICU) were analysed. Seventeen of the patients were suspected of having SCI, based on clinical and laboratory criteria. In these patients, Candida antigens and antibodies were analysed extensively. Ten patients had a positive Candida antigen (titre >1:16) determined by the latex agglutination assay Cand-Tec(R) and their median antibody titre was 1:160 in the indirect haemagglutination test (HAT). Seven antigen-negative patients had a median titre of 1:1280 (HAT). Forty-one of 42 colonized control patients had negative antigen titres and a median antibody titre of 1:160. The sensitivities and specificities were 58.8% and 97.6% for antigenemia, and 52.9% and 85.7% for antibody detection. These values reached 100.0% and 83.3%, respectively, when the results of both tests were combined. This indicates a high degree of concordance between serological results (Candida antigen and/or antibodies) and clinical presentation. We conclude, that the combined investigation of antigen and antibody titres might be a helpful tool in the characterization of SCI in ICU patients, if antigen titres are >or=1:16 or antibody titres (HAT) are >or=1:640.

Adolescent↗
PubMed2001

Candida colonization in mechanically ventilated patients.

The diagnosis of pulmonary candidosis is controversial. We undertook a prospective study on 50 mechanically ventilated (>48 h) patients who were hospitalized (>72 h) in the intensive care unit (ICU) with the aim of assessing the incidence of the isolation of Candida species from endotracheal aspirates (EA). Patients were categorized as individuals already colonized with Candida spp. on admission, individuals becoming colonized during hospitalization, or patients with no colonization. Patients in the ICU were hospitalized for a mean of 23 days. The percentage of patients already colonized with Candida was low (six of 50; 12%), the incidence of Candida isolation from EA in critically ill, mechanically ventilated patients in ICU was also low (six of 50; 12%). Age, duration of hospitalization, pre-treatment with antimicrobials or immunosuppressive agents and occurrence of underlying disease were not risk factors in our study. Both antifungal usage and neutropenia were more common in already colonized patients. No risk factors were determined for patients colonized during hospitalization. As all the isolates identified were C. albicans. It appears that at present, colonization and/or infection by more resistant Candida species is not a problem in our unit.

Candida↗
PubMed2002

Testing chemical germicides against Candida species using quantitative carrier and fingerpad methods.

Six disinfectants were tested against Candida albicans, C. parapsilosis and C. tropicalis using quantitative carrier tests based on glass (QCT-1) and metal (QCT-2) surfaces. C. albicans was also used to test four topical agents by a fingerpad method. Hard water (200 ppm as CaCO(3)) was the product diluent. In preliminary tests with QCT-1 and QCT-2, the testing was with or without a soil load; subsequent tests and fingerpad tests included soil. In QCT-1 and QCT-2, each carrier received 10 microL (5.0 x 10(6) - 1.0 x 10(7)colony forming units) of Candida, and was air dried for 1 h, then exposed to 1 mL or 50 microL of test product at 22 +/- 2 degrees C for up to 10 min. Controls received an equivalent volume of saline. For fingerpad tests, each digit received 10 microL of inoculum, which was allowed to dry and exposed to 1 mL of test product for 20 s. Inoculated plates of Sabouraud's dextrose agar were held for 48 h at 30 degrees C and colonies counted to determine reductions in colony forming units. In tests on both hard surfaces and fingerpads, ethanol and products based on ethanol reliably and rapidly inactivated all the Candida species tested. Products with sufficient potency to have tuberculocidal claims produced substantial reductions in the titre of C. albicans, although some showed a lesser reduction in titre of C. tropicalis and C. parapsilosis. This may reflect differences in cell hydrophobicity between Candida species, and highlights the need for care in selecting a suitable surrogate for disinfectant tests. The quantitative carrier and fingerpad protocols are suitable for assessing the activity of disinfectants and topical antiseptics against candida.

Anti-Infective Agents, Local↗
PubMed2002

Non-albicans Candida infections in patients with hematologic malignancies.

The epidemiology of invasive Candida infections is characterized by a recent decline in Candida albicans and C. tropicalis with a concomitant increase in the incidence of non-albicans Candida species such as C. glabrata and C. krusei, a phenomenon at least partly ascribed to triazole use. Of particular concern is the recognition that these organisms are multiresistant, adding a new dimension to the challenge of management. C. lusitaniae, though uncommon, mainly presents as breakthrough fungemias in patients on antifungal therapy. C. parapsilosis, an organism of relatively low virulence, plays an increasing role because of its ability to cause intravenous line and hyperalimentation fluid colonization. Emergence of azole-resistant (relative or absolute) Candida species is being met by a new class of antifungal agents namely the echinocandins and a new generation of broad-spectrum triazole agents. This article addresses the biology, epidemiology, prognostic factors, and management of an emerging group of pathogens such as non-albicans Candida.

Antifungal Agents↗
PubMed1991

Detection of circulating candida enolase by immunoassay in patients with cancer and invasive candidiasis.

BACKGROUND: Invasive candidiasis is a major nosocomial infection that is difficult to diagnose. Few biochemically defined markers of invasive candidiasis are known. Initial findings suggested that the presence of candida enolase in the blood may be a novel marker for invasive candidiasis. METHODS: We tested 170 patients at high risk for invasive candidiasis for candida enolase antigenemia. All the patients had cancer and neutropenia. We detected antigen using a double-sandwich liposomal immunoassay for candida enolase in serially collected serum samples. Invasive candidiasis was proved by finding candida species in deep nonmucosal tissue, blood cultures, or both. Antigen testing was performed with the investigator blinded to tissue or culture diagnosis. RESULTS: Among 24 patients with proved invasive candidiasis, 149 serum samples were tested for enolase antigenemia; 80 were positive and 69 negative (sensitivity per sample, 54 percent). Multiple sampling improved the detection of antigenemia, which was found in 11 of 13 proved cases of deep tissue infection (85 percent) and in 7 of 11 proved cases of fungemia (64 percent). Specificity was 96 percent as measured against control groups including patients with mucosal colonization, bacteremia, and other deep mycoses. Antigenemia was detected in the absence of fungemia in 5 cases of deep tissue candidiasis, but was not detected in 6 cases of fungemia alone. CONCLUSIONS: Candida enolase antigenemia is a novel marker for invasive candidiasis. It may be a useful indicator of deep infection in patients with cancer and neutropenia and may complement the diagnostic usefulness of blood cultures.

Antigens, Fungal↗
PubMed2001

Detection of Candida species by polymerase chain reaction (PCR) in blood samples of experimentally infected mice and patients with suspected candidemia.

In this study, we have established and evaluated a genus-specific polymerase chain reaction (PCR) and species-specific nested PCRs for the detection of Candida species in blood samples of neutropenic mice and patients suspected of candidemia. DNA segments of the gene encoding cytochrome P450 L1A1 were targeted for amplification by using genus and species-specific primers. As compared to the genus-specific PCR, the species-specific nested PCRs improved the sensitivity by 10 times with the detection limit < 10 yeast cells. Of the 18 blood samples tested daily over a period of 8 days following Candida albicans infection in neutropenic mice, four samples were positive by genus-specific PCR and 11 were positive by species-specific nested PCR. The PCR results were correlated with culture findings obtained on blood samples. Two of the three blood culture-positive samples were positive by genus-specific PCR and all the three with species-specific nested PCR. Among 15 mice, which were negative by blood culture but had C. albicans isolated from visceral organs, 2 and 8 mice yielded positive results by genus-specific PCR and species-specific nested PCR, respectively. Consistent with the results of the animal study, species-specific nested PCR yielded much higher positivity as compared to culture (52.2% versus 21.2%) in patients suspected for candidemia. Moreover, 8 specimens which were negative for Candida by genus-specific PCR became positive by species-specific nested PCR. No correlation was apparent between PCR positivity and Candida antigen titers. The results suggest that nested PCR is a sensitive technique for the detection of Candida species from blood samples, and thus it may have application in the diagnosis of suspected cases of candidemia and candidiasis.

Animals↗
PubMed2005

The in vitro activity of vaginal Lactobacillus with probiotic properties against Candida.

Lactobacilli, the predominant vaginal microorganisms in healthy premenopausal women, control other members of the vaginal microflora and thus protect against bacterial vaginosis and urinary tract infections. It has been claimed that some lactobacilli are also protective against Candida vaginitis. Little is known, however, about the mechanisms by which these lactobacilli can control vaginal populations of Candida and prevent vaginitis. To address this question, vaginal Lactobacillus strains with known antagonistic properties against bacteria were tested for their cell surface properties, adhesion to vaginal cell lines in vitro and antagonistic activities against Candida. A small proportion of the lactobacilli tested adhered strongly to cultured vaginal epithelial cells and inhibited growth of Candida albicans but not of C. pseudotropicalis. This anticandidal activity was in some Lactobacillus strains related to hydrogen peroxide (H2O2) production, but catalase treatment did not suppress this activity in other Lactobacillus strains, suggesting alternative mechanism(s). Moreover, tested vaginal Candida strains were resistant to relatively high concentrations of H2O2 that markedly exceeded those produced by even the most active Lactobacillus strains.

Bacterial Adhesion↗
PubMed1994

Fluconazole, itraconazole and ketoconazole in vitro activity against Candida spp.

The in vitro activity of fluconazole, itraconazole and ketoconazole against 625 Candida yeast strains from patients treated at the University Hospital of the Canaries, by means of a micromethod of dilution in broth enriched with Yeast Nitrogen Base (YNB), and buffered to pH7, has been assessed. Species distribution was as follows: Candida albicans (388), Candida tropicalis (84), Candida glabrata (84), Candida parapsilosis (69). Our results show 10.0% and 8.8% of C. albicans resistant to itraconazole and fluconazole, respectively, and 1.8% resistant to ketoconazole; 39.5% of C. tropicalis were resistant to itraconazole, 34.5% to fluconazole and 2.4% to ketaconazole. 19.1% of C. glabrata were resistant to fluconazole and 13.1% to itraconazole; 4.4% of C. parapsilosis were resistant to fluconazole and 1.5% to itraconazole. In general C. tropicalis was the most resistant strain and C. parapsilosis the most sensitive. The greatest percentages of resistance in vitro were seen with the two triazols.

Candida↗
PubMed2005

Vital growth factors of Malassezia species on modified CHROMagar Candida.

A comparison of several media, i.e., potato dextrose agar with olive oil (Oil-PDA), modified Dixon agar (mDIX) and variations of Leeming and Notman agar (LNA) for the isolation and growth of Malassezia and Candida species was examined. Since LNA supported the highest growth of Malassezia species its key components, i.e., ox bile, glycerol monostearate, glycerol and Tween 60, were added to CHROMagar Candida. All 7 species of Malassezia grew well on this modified medium (LN-CHROM) after incubation for 4 days at 30 degrees C and development was equal to that observed on LNA. Colonies on LN-CHROM were smooth and from pink to dark purple in color. Furthermore, the use of LN-CHROM did not alter the colony characteristics of Candida species as compared to that found on CHROMagar Candida. The results of the present investigation indicate that the use of LN-CHROM would make possible the simultaneous isolation and identification of Malassezia and Candida species.

Bile↗
PubMed2000

Growth inhibition of Candida by human oral epithelial cells.

Oropharyngeal candidiasis (OPC) caused by Candida albicans is a significant problem in human immunodeficiency virus (HIV)-infected persons. Recognizing the paucity of information on innate and/or adaptive mucosal host defenses against C. albicans, we recently reported that human and nonhuman primate and mouse vaginal epithelial cells inhibit the growth of C. albicans in vitro. In the present study, oral epithelial cells collected from saliva of healthy volunteers and a purified oral epithelial cell line were found to inhibit blastoconidia and/or hyphal growth of several Candida species. Cell contact was a strict requirement for the epithelial cell anti-Candida activity; neither saliva nor culture supernatants alone inhibited Candida growth, and addition of saliva to the coculture did not modulate the epithelial cell activity. Finally, epithelial cell anti-Candida activity was significantly lower in HIV-infected persons with OPC. Together, these results suggest that oral epithelial cells may play a role in innate resistance against OPC.

Adult↗
PubMed2001

Growth inhibition of Candida albicans by human vaginal epithelial cells.

Vulvovaginal candidiasis (VVC) is a common mucosal infection caused by Candida species in women of childbearing age. Although acute VVC affects a large number of women and is often precipitated by hormonal fluctuations involving high estrogen levels, recurrent VVC (RVVC) affects another 5%-10% of women without any known predisposing factors. We have recently reported that vaginal epithelial cells from nonhuman primates and mice inhibit the growth of Candida albicans in vitro, which may represent an innate host defense mechanism against C. albicans at the vaginal mucosa. In the present study, we show that vaginal epithelial cells collected from healthy women with no history of VVC also exhibit anti-Candida activity, with no differences in activity at various stages of the menstrual cycle. Women diagnosed with RVVC, on the other hand, have reduced epithelial cell anti-Candida activity. These results are further evidence that vaginal epithelial cells provide an innate host resistance mechanism against Candida and that reduced activity may contribute to RVVC.

Adult↗
PubMed2006

Improved clinical outcome of patients with Candida bloodstream infections through direct consultation by infectious diseases physicians in a Japanese university hospital.

OBJECTIVE: To examine whether intervention by infectious diseases physicians (IDPs) in the treatment decisions that emphasize adequate antifungal treatment and early removal of central venous catheter for patients with Candida bloodstream infection (BSI) improves prognosis. DESIGN: Retrospective cohort study of patients with Candida BSI, comparing the prognosis of patients before and after the start of the intervention. SETTING: A 1,240-bed, tertiary care university hospital. PATIENTS: Forty patients with Candida BSI during a 2-year period, from January 2001 to December 2002, were included in the study. Twenty-three patients in the first year after the start of intervention by IDPs (intervention group) were compared with 17 patients in the first year before the start of the IDP intervention (baseline group). INTERVENTIONS: In January 2002, a total of 5 IDPs at Kyoto University Hospital gave unsolicited recommendations on antifungal treatment and advised all physicians treating inpatients who had Candida BSI to remove the central venous catheter. RESULTS: No significant difference was seen between the 2 groups in patients' clinical background, species, and fluconazole susceptibility of the causative organisms. The 30-day survival rate was significantly better in the intervention group (18 [78%] of 23 patients) than in the baseline group (7 [44%] of 16 patients; P=.04 by Fisher's exact test). More patients in the intervention group than in the baseline group received appropriate antifungal therapy (81% vs 50%) and had their central venous catheter removed at an appropriate time (95% vs 81%). CONCLUSION: The introduction of an active system of IDP consultation for every case of Candida BSI in our hospital substantially improved patient outcomes.

Adult↗
PubMed1997

The epidemiology of hematogenous candidiasis caused by different Candida species.

The medical records of patients with hematogenous candidiasis at M. D. Anderson Cancer Center (Houston) between 1988 and 1992 were retrospectively reviewed. There were 491 episodes of infection (6 per 1,000 admissions), 79% of which occurred outside the intensive care unit setting. A significant decrease in incidence was observed among patients with leukemia over the study period, together with a relative decrease in Candida albicans and Candida tropicalis infections and an increase in Candida krusei and possibly Candida glabrata infections. In the multivariate analysis, fluconazole prophylaxis provided strong protection against the development of C. tropicalis infection (odds ratio [OR] = 0.08) and C. albicans infection (OR = 0.15), in comparison with protection against infections due to other species, but it was the single most important determinant for the relative increase in C. krusei (OR = 27.07) and C. glabrata (OR = 5.08) infections. In conclusion, there has been a substantial shift in the epidemiology of hematogenous candidiasis caused by different Candida species in recent years. Fluconazole appears to be playing a major role in this observed shift.

Adult↗
PubMed1997

Use of electrophoretic karyotyping in the evaluation of Candida infections in a neonatal intensive-care unit.

OBJECTIVE: To evaluate a possible common-source outbreak of Candida infections in the neonatal intensive-care unit. Systemic Candida infections increased from 6 to 11 cases (0.71 to 1.34 per 1,000 patient-days). In addition, Candida parapsilosis infections increased from 1 in 1992 to 10 in 1993. DESIGN AND SETTING: Tertiary-care, teaching, pediatric institution with a 40-bed neonatal intensive-care unit (NICU). Clinical characteristics, associated conditions, and antimicrobial therapy were obtained from the medical records of all NICU patients with positive blood cultures for Candida during 1992 and 1993. Nineteen Candida isolates from 15 infants were studied retrospectively using contour-clamped homogeneous electric-field (CHEF) electrophoresis. RESULTS: CHEF revealed eight karyotypes of C parapsilosis. Five isolates recovered from four patients shared one karyotype. The remaining isolates from seven infants all had distinctly different karyotypes. CONCLUSIONS: The evidence was insufficient to implicate a single source of infection, even though four patients in the same unit had identical strain types. However, identical strains of C parapsilosis were associated geographically, suggesting that nosocomial acquisition of C parapsilosis through indirect patient contact in the NICU was possible. The CHEF technique yields unique patterns that may be used to delineate clinical isolates and to study the molecular epidemiology of candidal infections.

Candida↗
PubMed2002

Emergence of nosocomial candidemia at a teaching hospital in Taiwan from 1981 to 2000: increased susceptibility of Candida species to fluconazole.

The incidence of nosocomial Candida fungemia increased 36-fold from 1981 (0.8/10,000 discharges) to 2000 (28.8/10,000 discharges) at the National Taiwan University Hospital, a 2000-bed teaching hospital in northern Taiwan. To understand the current status of resistance to available antifungal agents among Candida species causing invasive infections, the in vitro susceptibilities of 222 isolates (collected from July, 1999-June, 2001) were determined. Among all of the Candida species tested, 6% and 7% were resistant to fluconazole and itraconazole, respectively. The MIC90 values of voriconazole and amphotericin B were 0.5 and 1 microg/ml, respectively, although some isolates of C. krusei (amphotericin B and voriconazole MIC, >64 microg/ml) and C. tropicalis and C. glabrata (voriconazole MICs, >64 microg/ml) were less susceptible to voriconazole or amphotericin B. About one-half of the C. glabrata isolates belonged to susceptible dose-dependent (SDD, 36%) or resistant (12%) categories for fluconazole and 96% belonged to SDD (56%) or resistant (40%) category for itraconazole. When compared with fluconazole susceptibility data of blood Candida isolates recovered from patients treated at the same hospital (NTUH) from two different time periods (January, 1994, to June, 1995, and January, 1997, to June, 1999 described in previous reports), the incidence of increased susceptibility of non-krusei Candida isolates to fluconazole was evident. This trend of increasing susceptibility for fluconazole did not correlate to the increasing use of this agent in the hospital. None of the random amplified polymorphic DNA patterns generated by arbitrarily primed PCR using four random oligonucleotide primers for 14 isolates, which exhibited fluconazole MICs of > or = 16 microg/ml, were identical, indicating an absence of clonal dissemination among these isolates in the hospital.

Antifungal Agents↗
PubMed1997

Eight-year surveillance of non-albicans Candida spp. in an oncology department prior to and after fluconazole had been introduced into antifungal prophylaxis.

From 1989 until 1996, during the last 8 years, the proportion of Candida (C.) krusei, and other non-albicans Candida spp. isolated from surveillance cultures and from sterile body sites, was analyzed among 13,758 admissions in a National Cancer Institute. During these admissions a total of 9,042 isolates were prospectively collected from surveillance cultures, and 126 from blood cultures. The proportion of C. krusei among all organisms was 12.7% to 16.5% in 1989 through 1991, i.e., before fluconazole was introduced into prophylactic protocols. After the introduction of fluconazole into prophylaxis in acute leukemia in 1992 the incidence of C. krusei was 7.9% to 8.6% during 1994 to 1996. After 5 years of using this drug for prophylaxis, the incidence of C. krusei was lower than before this drug was introduced in our institute. Among yeasts, the most frequently isolated pathogen was still Candida albicans (72.2% of all isolated fungal organisms). Among molds, Aspergillus spp. was the most frequently isolated agent. Analyzing the etiology of proven fungal infections (fungemias) confirmed by positive blood cultures, C. albicans was the most common causative organism in 53.8% of cases. The incidence of fungemia due to Torulopsis (C.) glabrata and C. krusei before and after fluconazole introduction did not change. Of 126 organisms isolated from blood cultures, there was no increase in T. (C.) glabrata or C. krusei after introduction of fluconazole for prophylaxis and therapy, and the quoted 6.4% of fungemic episodes remained stable with an incidence of 1 fungemia/year since 1991. The proportion of C. krusei and C. glabrata among Candida spp. was decreasing in our center between 1989 and 1996. Also, the proportion of non-albicans Candida spp. among isolates decreased from 25.7% in 1990 to 11.9% in 1996.

Anti-Infective Agents↗
PubMed1990

A new slide latex agglutination test for the diagnosis of acute Candida vaginitis.

Two hundred two slide latex agglutination (SLA) tests were performed on 137 women attending a vaginitis clinic to evaluate the efficacy of this new test in diagnosing acute symptomatic Candida vaginitis. In 77 patients with acute Candida vaginitis, the SLA test revealed a positive reaction in 56 patients, reflecting a sensitivity of 72.7%, lower than that observed with the 10% potassium hydroxide microscopic examination (sensitivity 90%). False negative SLA reactions could not be accounted for by lower numbers of yeast cultured from the vagina or by the presence of nonalbicans strains of Candida. Following successful antimycotic therapy, the SLA test promptly became negative in all mycologically negative patients. Application of the SLA test in asymptomatic healthy control women revealed extremely few false positive reactions for Candida (5.6%). This easily performed and rapid slide latex agglutination test should provide a useful adjunct to the diagnosis of Candida vaginitis, but only for physicians who do not routinely perform microscopy on vaginal secretions.

Antigens, Fungal↗