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PubMed1997

Candida dubliniensis: an emerging opportunistic pathogen.

The incidence of opportunistic fungal infections continues to increase, partly as a result of the continuing AIDS epidemic. Candida albicans remains the most important fungal pathogen and is frequently associated with oral candidiasis in HIV-infected individuals. Over the past decade, however, there has been an increasing number of reports implicating other Candida species, such as C. tropicalis, C. glabrata and C. krusei, in disease in these patients and in other patient groups. During the same period there have also been frequent reports in the literature describing what have generally been termed "atypical" C. albicans strains. These isolates have usually been recovered from symptomatic HIV-infected individuals and are unidentifiable as any recognized Candida species using conventional criteria. Two such groups of isolates recovered from cases of oral candidiasis in Irish and Australian HIV-infected and AIDS patients have been postulated to constitute a novel species which has been termed C. dubliniensis. These isolates are phenotypically very similar to C. albicans in that they produce germ tubes and chlamydospores. However, they have unusual carbohydrate assimilation patterns and grow poorly or not at all at 42 degrees C. Using a variety of DNA fingerprinting techniques and karyotype analysis, the genomic organization of C. dubliniensis was shown to be distinctly different from that of C. albicans. Classification of C. dubliniensis as a separate species was confirmed by phylogenetic analysis, whereby the comparison of ribosomal RNA sequences demonstrated that C. dubliniensis isolates formed a cluster clearly distinct from other Candida species, including C. albicans, to which it is most closely related. Since its original identification, atypical Candida isolates from around the world have been positively identified as belonging to this species. To date, isolates of C. dubliniensis have been recovered mainly from the oral cavities of HIV-infected individuals and are most frequently implicated in cases of recurrent infection following antifungal drug treatment. The clinical importance of this species and the role of drug resistance in its epidemiology have yet to be determined.

AIDS-Related Opportunistic Infections↗
PubMed1997

Evaluation of CHROMagar Candida medium for the isolation and direct identification of yeast species from the female genital tract.

The performance and cost-effectiveness of CHROMagar Candida in the isolation and identification of Candida species from female genital tract specimens were investigated. Eight hundred and forty-three specimens were inoculated in parallel onto malt extract agar and CHROMagar Candida. Yeasts isolated on CHROMagar were provisionally identified by morphology and pigmentation. Those isolated on malt extract agar were further identified by a germ tube test, and negative isolates were identified biochemically. A cost comparison was performed, detailing labour and material costs. Of 119 yeast isolates, seven were detected only on CHROMagar. Mixed Candida spp. from three specimens were only differentiated on CHROMagar. There was a 100% correlation between the results of the germ tube test and provisional identity on CHROMagar. CHROMagar Candida facilitated the presumptive identification of yeast isolates from the female genital tract, and the detection of mixed populations. The cost of the media was higher than malt extract agar and germ tube testing, but the rapid identification of isolates to species level and ease of use may be of sufficient advantage to justify the extra cost.

Candida↗
PubMed2006

Presence of mutans streptococci and Candida spp. in dental plaque/dentine of carious teeth and early childhood caries.

This study determined the presence of mutans streptococci and Candida spp. in supragingival dental plaque and infected dentine of caries-free children, with early childhood caries and caries. Pooled samples of dental plaque and infected dentine were collected from 56 children aged 1-5 years, which were divided into 3 groups: early childhood caries (ECC); caries and caries-free. Infected dentine was collected in ECC and caries groups to compare the frequency of these microorganisms in the collected sites. The samples were inoculated in SB20 and SA medium, for mutans streptococci and Candida spp., respectively, and incubated at 37 degrees C for 48 h. Colony growth was verified and the identification was performed by biochemical tests and CHROMagar Candida. Fisher's test or chi-square (chi(2)) were applied (p=0.05). The more prevalent species were S. mutans and Candida albicans in ECC (85.4% and 60.4%, respectively), independently of the sample site. S. mutans only was significantly associated with carious teeth, whether in early childhood caries or not. However, the frequency of C. albicans in ECC was higher when compared to caries and caries-free groups. There is a significant association between the presence of C. albicans and early childhood caries.

Candida↗
PubMed2003

Comparative evolutionary genomics unveils the molecular mechanism of reassignment of the CTG codon in Candida spp.

Using the (near) complete genome sequences of the yeasts Candida albicans, Saccharomyces cerevisiae, and Schizosaccharomyces pombe, we address the evolution of a unique genetic code change, which involves decoding of the standard leucine-CTG codon as serine in Candida spp. By using two complementary comparative genomics approaches, we have been able to shed new light on both the origin of the novel Candida spp. Ser-tRNA(CAG), which has mediated CTG reassignment, and on the evolution of the CTG codon in the genomes of C. albicans, S. cerevisiae, and S. pombe. Sequence analyses of newly identified tRNAs from the C. albicans genome demonstrate that the Ser-tRNA(CAG) is derived from a serine and not a leucine tRNA in the ancestor yeast species and that this codon reassignment occurred approximately 170 million years ago, but the origin of the Ser-tRNA(CAG) is more ancient, implying that the ancestral Leu-tRNA that decoded the CTG codon was lost after the appearance of the Ser-tRNA(CAG). Ambiguous CTG decoding by the Ser-tRNA(CAG) combined with biased AT pressure forced the evolution of CTG into TTR codons and have been major forces driving evolution of the CTN codon family in C. albicans. Remarkably, most of the CTG codons present in extant C. albicans genes are encoded by serine and not leucine codons in homologous S. cerevisiae and S. pombe genes, indicating that a significant number of serine TCN and AGY codons evolved into CTG codons either directly by simultaneous double mutations or indirectly through an intermediary codon. In either case, CTG reassignment had a major impact on the evolution of the coding component of the Candida spp. genome.

Amino Acid Sequence↗
PubMed2006

Clinical and experimental evaluation of a new chromogenic medium (OCCA, Oxoid) for direct identification of Candida albicans, C. tropicalis and C. krusei.

Oxoid Chromogenic Candida Agar (OCCA) is a new commercial ready-to-use medium that contains chromogenic substrates for rapid detection and specific identification of Candida albicans, C. tropicalis and C. krusei. We evaluated the performance of this medium with 364 clinical specimens and 31 subcultures, and examined its ability to support the growth of small inocula of six reference strains. CHROMagar Candida was used as the reference medium. OCCA permitted the growth of most important yeasts, and readily discriminated among Candida spp. in clinical specimens, including mixed cultures.

Candida↗
PubMed2004

Oral colonization of Candida species in perinatally HIV-infected children in northern Thailand.

Human immunodeficiency virus (HIV) infection remains a serious problem in northern Thailand. A high prevalence of perinatally HIV-infected children with oral candidiasis has been observed in the region. The objective of this study was to determine oral colonization of Candida spp. in children with perinatal HIV infection. Samples were collected by oral rinse or oral swab from 40 HIV-infected children and from 15 HIV-negative children as a control group. Yeasts recovered in culture were identified and quantified. The mean ages of HIV-infected children and HIV-negative children were 5.5 years (SD = 3.5) and 2.9 years (SD = 2.0) respectively. Eighteen HIV-infected children (45%) had clinical symptoms of oral candidiasis while none of the HIV-negative children had any such symptoms. By culture technique, yeasts were isolated from 28/40 (70%) of the HIV-infected children and 6/15 (40%) of the HIV-negative children. C. albicans was the most common species recovered from HIV-infected and HIV-negative children. Statistically, HIV infection was significantly associated with Candida spp. detection (P-value = 0.04). In contrast, the association between HIV infection and asymptomatic oral carriage of Candida spp. was not significant (P-value = 0.74). These findings demonstrate that oral colonization of Candida spp. is prevalent in HIV-infected children and suggest that prevention and treatment of oral candidiasis is needed for these children.

AIDS-Related Opportunistic Infections↗
PubMed2001

Temporal assessment of Candida risk factors in the surgical intensive care unit.

HYPOTHESIS: Risk factors for Candida infection in surgical intensive care units (SICUs) change over time. Risk factor progression may influence Candida colonization and infection. DESIGN: Multicenter cohort survey. SETTING: Three urban teaching institutions. PATIENTS: A total of 301 consecutively admitted patients in SICUs for 5 or more days. MAIN OUTCOME MEASURES: Assessment of patients on SICU days 1, 3, 4, 6, and 8 and SICU discharge for risk factors, Candida colonization, and antifungal use. Candida colonization status was categorized as noncolonized (NC), locally colonized (LC) if 1 site was involved, and disseminated infection (DI) if 2 or more sites or candidemia were involved. RESULTS: The most frequent risk factors in the 301 patients enrolled were presence of peripheral and central intravenous catheters, bladder catheters, mechanical ventilation, and lack of enteral or intravenous nutrition. Early risk factors included total parenteral nutrition or central catheter at SICU day 1 and previous SICU admissions or surgical procedures. Peak number of risk factors (mean +/- SD) were as follows: 7.2 +/- 2.6 in NC (n = 229), 9.2 +/- 2.3 in LC (n = 45), and 9.2 +/- 2.6 in DI (n = 27). These numbers were reached at day 8 in the NC and LC groups and day 4 in the DI group. The LC and DI groups had more risk factors on each SICU day than the NC group and longer median SICU length of stay (28 days in the DI group vs 11 and 19 days in the NC and LC groups, respectively). Antifungal therapy, while used most frequently in the DI group, was initiated later for this group than in NC and LC groups. CONCLUSIONS: Risk factors for Candida infection in SICU patients change over time. Patients with DI demonstrate a greater number of and more rapid increase in risk factors than patients in the LC and NC groups. Presence of early risk factors at the time of SICU admission, a high incidence of risk factors, or a rapid increase in risk factors should prompt clinicians to obtain surveillance fungal cultures and consider empirical antifungal therapy.

APACHE↗
PubMed1993

Impaired polymorphonuclear leukocyte anticandidal function in injured adults with elevated Candida antigen titers.

Per protocol, adults with an Injury Severity Score of 18 or greater underwent Candida antigen titer measurements weekly. If titers were 1:4 or greater, neutrophil function against Candida albicans was determined with use of a tritiated glucose incorporation assay, and polymorphonuclear leukocytes obtained from healthy blood donors were studied concurrently for comparison. Polymorphonuclear leukocytes from healthy blood donors and injured patients with elevated titers were able to inhibit C albicans growth in a dose-dependent fashion. Polymorphonuclear leukocytes from injured patients with elevated titers had a significantly depressed ability to inhibit Calbicans growth compared with those from healthy blood donors at all effector cell-to-target cell ratios tested. Cytokine-treated polymorphonuclear leukocytes from healthy blood donors and injured patients with elevated Candida antigen titers demonstrated significantly improved anticandidal activity at all ratios of polymorphonuclear leukocytes-to-Candida. Granulocyte macrophage-colony stimulating factor was the most potent cytokine at reconstituting polymorphonuclear leukocyte function, followed by interferon gamma and interleukin 8. In conclusion, an elevated Candida antigen titer in injured adults is associated with impaired polymorphonuclear leukocyte antifungal activity. This depressed activity can be reconstituted by the addition of cytokine.

Adult↗
PubMed1999

Candida infection in pediatric liver transplant recipients.

A retrospective review of 100 liver transplantations in 98 children was performed to determine the incidence of infection caused by Candida organism in these patients and to identify risk factors that may predispose to serious fungal infection. Thirty-one infections caused by Candida organisms developed during the initial 28 days posttransplantation: 19 were definite invasive infections (one deep site or one positive blood culture), 2 were probable invasive infections (three superficial sites), and 10 were urinary tract infections. Eleven of 19 patients had fungemia or a disseminated infection (two noncontiguous deep organs involved and/or positive blood cultures) and 8 of 19 had peritoneal candidiasis. Infection caused by Candida organisms was a contributing factor to mortality in 7 of 21 patients (case fatality rate of 33%) with invasive infection. Risk factors that were predictive for invasive infection by univariate analysis included the following: pretransplantation antibiotic therapy, length of transplant operation, transfusion requirement, number of days in the intensive care unit, number of days intubated, number of concurrent bacterial infections, number of antibiotics administered, number of laparotomies performed posttransplantation, retransplantation, hepatic artery thrombosis, bile leaks, and renal and respiratory failure. By logistic regression analysis, bile leak, hepatic artery thrombosis, preoperative steroid use, transfusion requirement, and the number of days intubated were identified as independent risk factors for invasive infection caused by Candida organisms. The use of prophylactic antifungal agents in high-risk patients may be important in reducing the serious morbidity and mortality associated with sepsis caused by Candida organisms in pediatric liver transplant recipients.

Adolescent↗
PubMed1997

Influence of temperature on the regulation and toxicity of zinc in Folsomia candida (Collembola).

To generate reproducible and reliable results, most protocols for standardized toxicity tests prescribe strict limits for test conditions such as temperature and relative humidity. In the field, however, variability of climate can influence the functioning of organisms and induce changes in sensitivity. To evaluate the influence of temperature on the ecotoxicity of zinc, the springtail Folsomia candida was exposed to zinc-contaminated soil at different temperatures. In one experiment, the toxicity of ZnCl2 was determined at a constant temperature and under alternating temperature conditions. Although control performance of F. candida was influenced by the temperature treatment, effect concentrations for reproduction were not significantly different between treatments. Levels of internal zinc regulation were higher in animals exposed to alternating temperatures. Based on the observed influence of temperature on the accumulation of zinc, a second experiment was performed to determine the sensitivity of F. candida to zinc at four different exposure temperatures. A decrease in temperature led to an increase in sensitivity when sublethal parameters such as growth and reproduction were considered. However, animals were less sensitive at lower temperatures where mortality was concerned. Internal zinc concentrations in the animals increased with decreasing temperatures, and when the effect on reproduction was based on internal zinc levels, differences between temperature treatments were not significant. From the results of this study it is concluded that for F. candida, constant temperature conditions form a good basis for the extrapolation of toxicity levels to fluctuating temperature conditions. Since the average exposure temperature can alter the sensitivity of F. candida for zinc, and changes in sensitivity are parameter dependent, exposure temperature should be chosen carefully.

Animals↗
PubMed1984

Studies on defense mechanisms against Candida albicans infection in congenitally athymic nude (nu/nu) mice.

The defense mechanisms against Candida albicans infection were studied by using a mouse thigh lesion model in congenitally athymic nude (nu/nu) mice and their normal littermates (nu/+). Nu/nu mice were more resistant to C. albicans infection than nu/+ mice judging from the course of the thigh lesion, the results of CFUs (colony-forming units) of C. albicans in the lesion, and histopathological observations. Histopathological and serological studies revealed that granulocytic cellular infiltration was predominant, and there were few indications of development of cell-mediated immunity to protect Candida infection in Candida-infected nu/nu and nu/+ mice. These results confirmed that lower susceptibility of nu/nu mice to C. albicans infection as compared to nu/+ mice was due to accelerated non-specific defense mechanisms in nu/nu mice, and that cell-mediated or humoral immunity played a minor role in the defense against Candida infection in this experimental model. Furthermore, treatment with high titer of rabbit anti-C. albicans serum was effective to control the number of Candida cells in thigh lesions of BALB/c mice. Above experimental results seem to clearly indicate the great variability of defense manifestation according to the experimental model exployed.

Animals↗
PubMed1989

Mannan and D-arabinitol concentrations in serum from a patient with Candida albicans endocarditis.

In an attempt to clarify the comparative values of serological and microbiological examinations for the early diagnosis of systemic candidiasis, antibodies against Candida albicans, serum mannan, and the D-arabinitol creatinine ratio were investigated in a patient with aortic valve endocarditis associated with carcinoma of the bile duct. Candida precipitins and the antibody titer against Candida cell wall mannan were examined by an immunodiffusion technique and hemagglutination test, respectively. Serum mannan was tested by enzyme-linked immunosorbent assay (ELISA) using the biotin-streptavidin procedure. The upper limit of negativity of the assay was determined by adding 0.06 to the absorbance of pooled serum from healthy laboratory workers. This value was about 0.8 ng/ml with ELISA. The D-arabinitol concentration in serum was examined by an enzymatic fluorometric method. Rising antibody titers against C. albicans, mannan antigenemia, and an elevated D-arabinitol creatinine ratio were first observed between the 11th and 12th hospital days. Blood cultures obtained on 8th, 9th, and 11th hospital days grew C. albicans after 3 to 4 days of incubation. Of 11 serum samples, 5 were positive for mannan, whereas D-arabinitol creatinine ratio was positive in 7 of 9 samples. Blood cultures was the earliest evidence of Candida infections in our cases. However, because of saprophytic nature of Candida species, tests for antibodies, antigenemia, and the D-arabinitol creatinine ratio in combination with blood cultures are necessary to confirm systemic candidiasis at an early stage of infection.

Adenocarcinoma↗
PubMed1996

Endoscopic-pathologic correlates of Candida esophagitis in acquired immunodeficiency syndrome.

Although Candida esophagitis is one of the most common opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS), there has been no systematic study of the endoscopic and pathologic manifestations of this disease. During a 53-month period, 141 patients with AIDS and Candida esophagitis were studied. All patients had the severity of esophagitis graded prospectively and esophageal mucosal biopsies performed. Tissue biopsies were evaluated for histologic evidence of ulceration, extent of candidiasis, and presence of viral cytopathic effect. Follow-up was obtained. There appeared to be a uniform endoscopic appearance; with increasing severity, the scattered mucosal plaques coalesced, resulting in circumferential disease and luminal impingement. The pathologic pattern of Candida esophagitis was homogenous. Plaque material was composed primarily of desquamated superficial hyperplastic hyperkeratotic squamous epithelium and inflammatory cells, with infiltration by fungal elements and bacteria consistent with superinfection. Although endoscopic and histopathologic ulcer was commonly seen in these patients (32%), only four patients had ulcer believed secondary to Candida esophagitis alone. In conclusion, in patients with AIDS, Candida esophagitis is a superficial mucosal infection resulting in characteristic endoscopic and histopathologic patterns.

AIDS-Related Opportunistic Infections↗
PubMed1997

Benzydamine inhibits the release of tumor necrosis factor-alpha and monocyte chemotactic protein-1 by Candida albicans-stimulated human peripheral blood cells.

Benzydamine is a non-steroidal antiinflammatory drug, devoid of activity on arachidonic acid metabolism, which is extensively used as a topical drug in inflammatory conditions, particularly for the treatment of bacterial vaginosis and Candida albicans-sustained vaginitis. In the present study the effects of benzydamine on the production of several inflammatory cytokines were examined in cultures of Candida albicans-stimulated human mononuclear cells. Benzydamine (6.25-50 microM) inhibited Candida-induced tumor necrosis factor-alpha and, to a lesser extent, interleukin-1 beta production, whereas it did not affect interleukin-6 release. Benzydamine also blocked monocyte chemotactic protein-1 secretion, but it did not affect interleukin-8 production. Unlike benzydamine, ibuprofen and naproxen, two non-steroidal antiinflammatory drugs also used topically, were unable to suppress inflammatory lymphokine production from Candida-activated mononuclear cells. These data suggest that benzydamine may be effective in local Candida infections at least in part by suppressing inflammatory cytokine and monokine production in the vaginal mucosa and consequently decreasing their levels in vaginal secretions.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Candida glabrata fungemia in a tertiary cancer institution in Slovakia.

Because of controversial data on virulence and mortality, six cases of fungemia caused by Candida glabrata were reviewed in a single cancer institution within 8 years. Risk factors and outcome of C. glabrata, Candida albicans, and other non-albicans Candida spp. appearing within the same period under the same antibiotic policy at the same institution were compared. Among other non-albicans Candida spp. in 1990-1997 C. glabrata fungemias showed a decreasing tendency, from 9% to 4.5% in 1997. Analyzing the proportion of C. glabrata among blood cultures, among 170 positive blood cultures 12 were caused by C. glabrata (6.2% among all pathogens and 24% among non-albicans Candida spp.). C. glabrata among all fungemias was diagnosed as the fourth most common pathogen after C. albicans, C. krusei, and C. parapsilosis. Three of six C. glabrata fungemias were breakthrough. Two appeared during prophylaxis with itraconazole and one during fluconazole prophylaxis. Five of six received broadspectrum antibiotic therapy with third-generation cephalosporines, five of six had vascular catheter insertion, four of six were neutropenic, and two of six received amphotericin B therapy. One patient died before his blood cultures were reported to be positive. Overall mortality of C. glabrata fungemia was 16.7%. One patient died of underlying disease with fungemia. There were no significant differences in risk factors between C. glabrata and C. albicans. However, overall and crude mortality was lower in C. glabrata than in C. albicans (25.5% vs. 16.7%; P = 0.03). Attributable mortality was lower in comparison to C. albicans (0 vs. 15.7% in C. albicans; P = 0.001).

Journal Article↗
PubMed1986

Therapy of candidal vaginitis: the effect of eliminating intestinal Candida. Nystatin Multicenter Study Group.

A total of 258 patients with candidal vulvovaginitis, all of whom also exhibited Candida organisms in the rectum, were treated for 1 week with vaginal tablets only (nystatin or clotrimazole) or with both vaginal and oral tablets (nystatin). Mycologic and symptomatic responses were superior for the group receiving combined intravaginal-oral therapy; the vaginas of 88% of those treated by both routes were cleared of Candida, as compared with 75% of those receiving only intravaginal medication (p less than 0.05). Nystatin and clotrimazole were equally effective. When the 258 patients, regardless of treatment regimen, were grouped into those whose intestinal tracts after therapy contained Candida or those free of Candida, the response rates of the vaginal infection at all follow-up examinations favored the latter group (p less than 0.05 to less than 0.001). Vaginal infection recurred in 19.7% of patients treated only intravaginally and 14.7% of those receiving combined therapy. These results suggest the value of eliminating any intestinal reservoir of Candida when treating patients with candidal vulvovaginitis.

Administration, Oral↗
PubMed1993

Selective decontamination with nystatin for control of a Candida outbreak in a neonatal intensive care unit.

Selective decontamination of the digestive tract (SDD) with oral nystatin was evaluated as a measure to control an outbreak of Candida infection in a neonatal intensive care unit (NICU). Seventy-six out of 106 neonates who carried Candida spp. received the main study manoeuvre (the application of oral nystatin in the throat and stomach) during the 12-month open trial. One third of the neonates weighed < 1500 g whilst about half were being ventilated. The mean stay was 33.2 d (SD +/- 46.9). Two cases with candidaemia within a fortnight were associated with a yeast carriage rate in the NICU of about 50%; more than 80% of the isolates were Candida parapsilosis. During the implementation period there were four new neonates with fungaemia caused by C. parapsilosis. Once the carriage rate dropped below 5% (P < 0.001), no new cases of systemic infection with the outbreak strain were recognized in the following 8 months. It took 3.5 months to control the outbreak. The observation that all other clinical diagnostic samples were free from Candida suggests that translocation from throat or gut into the systemic circulation occurred. SDD with oral nystatin was effective in reducing the yeast carriage index (mean index 1.93, before SDD; 0.45, after SDD; P < 0.001). A significant reduction of carriage, both in rates and indices, is thought to have contributed to the control of this candida outbreak.

Candidiasis↗
PubMed1995

Management of candida septicaemia in a regional burn unit.

Sepsis due to candida infection is a major cause of mortality and morbidity on our unit. Over a period of 3 years and 4 months, 29 cases of candida septicaemia, diagnosed by blood cultures, were encountered at the burn unit at Augusta Regional Medical Center. Factors known to predispose to fungal sepsis were present in all cases. All patients had large burns (14-98 per cent total body surface (TBSA) with a mean of 48.3 per cent). All but one patient had at least one central venous line. Respiratory problems requiring ventilator support were present in 24 patients. Sixteen patients had Candida albicans sepsis, two in association with another fungal sepsis. Candida parapsilosis was encountered in nine patients, one in combination with another species. Four patients had Candida tropicalis. Amphotericin B was prescribed therapeutically in 25 patients, in seven together with fluconazole. Two patients received fluconazole only and two received no antifungal therapy. There were eight deaths all attributed to sepsis and all of whom had multiple organ failure. Five of those who died had completed a course of amphotericin B therapy, two were receiving treatment at the time of death, and one patient died before culture data became available. Early and aggressive therapy is advised and amphotericin B appears to be the drug of choice.

Adolescent↗