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Distribution and epidemiology of Candida species causing fungemia at a Saudi Arabian hospital, 1996-2004.

OBJECTIVES: The objective of this study was to evaluate the Candida species and the change over time in the organisms causing candidemia at Saudi Aramco Medical Services Organization in Saudi Arabia. We also describe the risk factors associated with mortality. METHODS: This was a retrospective study of candidemia over nine years (1996-2004). RESULTS: A total of 98 distinct episodes of candidemia were identified over the study period. The annual incidence of candidemia ranged between 0.2 and 0.76 cases/1000 hospital discharges with an incidence per 10 000 patient-days per year of 0.45 to 1.6. The most frequent Candida species were Candida albicans (53%), Candida tropicalis (19%), Candida parapsilosis (16%), and Candida glabrata (7%). In relation to predisposing factors, 83% of candidemia occurred in patients with central venous catheters and 96% had received broad-spectrum antibiotics. Other predisposing factors included complicated abdominal surgeries (22%), total parenteral nutrition (52%), neutropenia (9%), acute renal failure (24%), malignancy (26%) and burns (15%). However, prior fluconazole use was low (8%). The overall crude mortality rate was 43% for all candidemia. Logistic regression analysis identified two independent determinants of death, C. albicans (OR 5.91, 95% CI 1.50, 23.24, p=0.01) and acute renal failure (OR 5.15, 95% CI 1.18, 22.55, p=0.03). CONCLUSION: The study showed that the rate of candidemia was low in our hospital and that C. albicans was the major species followed by C. tropicalis and C. parapsilosis. Future studies are needed to evaluate the antifungal susceptibility pattern in our hospital.

Adult↗

Phenotypic characterization and in vitro antifungal sensitivity of Candida spp. and Malassezia pachydermatis strains from dogs.

Yeasts of the genera Candida and Malassezia can be found as commensal microorganisms in animals. The main species of importance in veterinary medicine are Malassezia pachydermatis and Candida albicans. The objectives of this study were to conduct a phenotypic characterization and to evaluate the in vitro antifungal sensitivity of strains of C. albicans (n=5), C. tropicalis (n=3) and M. pachydermatis (n=32) isolated from dogs. The phenotyping was based on macro and micromorphological features as well as biochemical analysis. The techniques of microdilution in broth and dilution in agar were used to evaluate the in vitro sensitivity of Candida spp. and M. pachydermatis, respectively. The tested drugs were ketoconazole (KTC), itraconazole (ITC), fluconazole (FLC) and amphotericin B (AMB). The morphological analysis of the strains of Candida spp. and M. pachydermatis did not show any noteworthy alterations when compared to standard strains. On the other hand, in the biochemical tests, 34.4% of the strains of M. pachydermatis were negative for the urease test. Four strains of C. albicans were resistant to FLC with a minimum inhibitory concentration (MIC) >64microg/mL and all were resistant to KTC and ITC (MIC>16microg/mL). The MIC for two strains of C. tropicalis were >16microg/mL for KTC and ITC, and >64microg/mL for FLC. It is worth highlighting that all of the strains tested were sensitive to AMB with the MIC varying from 0.25-1.0microg/mL. All strains of M. pachydermatis were sensitive to ITC with a minimum fungistatic concentration (MFC) 0.0075microg/mL. The MIC for 29 strains was the same (MFC0.0075microg/mL) for KTC. The MFCs for FLC varied from 1 to 16microg/mL, and for AMB, the MFC interval was 0.125-8microg/mL. There were no alterations in the classic phenotypic features of the strains of Candida spp. and M. pachydermatis isolated from dogs but, unlike M. pachydermatis, Candida spp. were much more resistant to azole antifungal agents.

Animals↗

Genetic diversity within the Albugo candida complex (Peronosporales, Oomycota) inferred from phylogenetic analysis of ITS rDNA and COX2 mtDNA sequences.

Albugo candida is a destructive fungus infecting brassicaceous hosts. The genetic diversity within the A. candida complex from various host plants was investigated by sequence analysis of the internal transcribed spacer (ITS) region of rDNA and the cytochrome c oxidase subunit II (COX2) region of mtDNA. The aligned nucleotide sequences of A. candida shared significantly high distances, up to 20.4 and 8.9%, in two genes. The phylogenetic trees, obtained using the Bayesian method and maximum parsimony analysis, showed two separate groups that corresponded to the host genera. Group I included A. candida isolates infecting Arabis, Autrieta, Berteroa, Biscutella, Brassica, Cardaminopsis, Diplotaxis, Eruca, Erysimum, Heliophila, Iberis, Lunaria, Raphanus, Sinapis, Sisymbrium, and Thlaspi. Group II contained all isolates from Capsella, Descurainia, Diptychocarpus, Draba, and Lepidium. The genetic similarities between the two genes among isolates within Group I were 99.0-100% and 99.6-100%, while those within Group II were 90.4-100% and 91.1-100%, respectively, showing considerably lower values than for Group I. The A. candida isolates from Capsella bursa-pastoris in Korea are clearly separated by sequence analysis for the two genes compared to those from Wales, England, and the USA. Based on the molecular data from the two genes, we suggest the high degree of genetic diversity exhibited within A. candida complexes warrants their division into several distinct species.

Base Sequence↗

Epidemiology and outcomes associated with moderate to heavy Candida colonization during pregnancy. Vaginal Infections and Prematurity Study Group.

OBJECTIVE: Our purpose was to determine the risk factors, physical findings, microflora, and pregnancy outcome among pregnant women with moderate to heavy vaginal growth of Candida albicans and other Candida species. STUDY DESIGN: A multicenter cohort of 13,914 women were enrolled between 23 and 26 weeks' gestation. Women completed a questionnaire, underwent a physical examination, and had genital specimens taken for culture. A subset of 1459 women were reexamined during the third trimester. Pregnancy outcomes were recorded at delivery. RESULTS: The prevalence of moderate to heavy Candida colonization at midgestation was 10%. Colonized women, 83% of whom carried C. albicans, were more likely to be black or Hispanic, unmarried, a previous oral contraceptive user, and to manifest clinical signs indicative of Candida carriage. Candida colonization was positively associated with Trichomonas vaginalis, group B streptococci, and aerobic Lactobacillus and was not associated with adverse pregnancy outcome. CONCLUSION: These results suggest that Candida colonization is not associated with low birth weight or preterm delivery.

Animals↗

Outbreak of Candida bloodstream infections associated with retrograde medication administration in a neonatal intensive care unit.

An outbreak of candidemia involving five infants receiving total parenteral nutrition in the neonatal intensive care unit was investigated. Cultures of the intravenous fluids demonstrated that the retrograde medication syringe fluids were significantly more likely to be contaminated with Candida than were other fluids being administered to the infants (p less than 0.001). Candidemia was significantly associated with total parenteral nutrition (p = 0.04) and retrograde medication administration (p = 0.02). A survey of nursing practice found that reuse of the retrograde syringes was the most likely cause of contamination. Molecular typing showed that the strains of Candida albicans that were isolated from the bloodstream were also found in the retrograde syringes and that at least three strains of C. albicans and one strain each of Candida tropicalis and Candida parapsilosis were involved. In vitro growth curves demonstrated that Candida species had a selective growth advantage versus bacteria in the total parenteral nutrition fluid. An in vitro simulation of the retrograde medication administration system suggested that the outbreak probably developed after the frequency of changing intravenous tubing was decreased from every 24 hours to every 72 hours. The outbreak was terminated by using syringes only once and resuming intravenous tubing changes every 24 hours. Retrograde medication administration in association with total parenteral nutrition may increase the risk of Candida line infection.

Candida↗

Endotracheal colonization with Candida enhances risk of systemic candidiasis in very low birth weight neonates.

OBJECTIVE: To determine whether growth of Candida from an endotracheal aspirate identifies a population of very low birth weight (VLBW; < or = 1500 gm) neonates at increased risk of systemic candidiasis. DESIGN: Prospective evaluation with weekly cultures of endotracheal and rectal specimens to determine colonization status. SUBJECTS: One hundred sixteen VLBW neonates (mean birth weight, 975 +/- 23 gm, estimated gestational age, 27.6 +/- 0.2 weeks) with endotracheal tubes in place who were admitted to a level III nursery between Jan. 8 and Dec. 2, 1992. RESULTS: Of the 116 subjects, 39 infants were colonized with Candida (34%). Thirteen neonates had growth of Candida in one or more cultures of endotracheal specimens. Eleven of these could be examined, and in five systemic disease developed (disease in 5/11 vs 2/26; relative risk = 5.9; 95% confidence interval, 1.34 to 26). Eight infants were colonized with Candida in the first week of life. Seven of these could be examined, and in five systemic candidiasis developed (disease in 5/7 vs 2/30; RR = 9.3; 95% confidence interval, 2.3 to 38.0). CONCLUSIONS: Colonization with Candida occurs frequently in VLBW infants. Progression from colonization to systemic infection is more common in the smallest neonates. Detection of colonization in the first week of life or the growth of Candida from an endotracheal aspirate identifies a group of VLBW neonates with an endotracheal tube in place whose risk of systemic candidiasis is increased. A prospective trial of intervention in this high-risk population is warranted.

Analysis of Variance↗

Phylogenetic relationship and mode of evolution of yeast DNA topoisomerase II gene in the pathogenic Candida species.

We have determined the nucleotide sequences of about 55% of the region of the DNA topoisomerase II gene (approximately 2.3 kb) isolated from the pathogenic Candida species, C. dubliniensis, C. parapsilosis, C. tropicalis, C. krusei, C. kefyr, C. guilliermondii and C. lusitaniae. Evolutionary relationships among nine Candida species including those of C. albicans and C. glabrata were studied based on the DNA topoisomerase II gene. The nucleotide sequences of 2192 bp, which covered two catalytic domains, ATPase and cutting/resealing, were subjected to phylogenetic analysis. Sequence comparison and evolutionary analysis have revealed that the Candida species tested here are not monophyletic, and the two strains within the species C. tropicalis and C. parapsilosis are too diverse to be in a single species. A wide variety of divergence was observed among the functional domains of DNA topoisomerase II, suggesting that Candida species were in different evolutionary paths at least as regarding the DNA topoisomerase II gene. Sequence information and the observation on the species-specific manner of molecular evolution of DNA topoisomerase II in Candida will be applied to develop a method of identification and characterization of the Candida species in both natural and clinical isolates.

Candida↗

Clinical evaluation of resilient denture liners. Part 2: Candida count and speciation.

PURPOSE: The purpose of this study was to count and to speciate Candida isolated from 2 resilient denture liners, Molloplast-B and MPDS-SL. MATERIALS AND METHODS: A group of 20 patients each had 1 maxillary denture and 2 mandibular dentures fabricated. One mandibular denture was lined with Molloplast-B, and 1 was lined with MPDS-SL. Each denture was used for 3 months. At the end of the 3-month period, the mandibular denture was surrendered, and a 5 x 5-mm circular resilient liner sample was obtained from the tissue surface of the lingual flange. Samples were processed, and Candida was isolated and counted. Speciation of Candida was performed using CHROMagar Candida and API 20C AUX strips. RESULTS: Molloplast-B had, on average, 5 times as many CFU/sample as MPDSL-SL, but this difference was not significant (p = 0.26). A sign test gave a similar nonsignificant trend (p = 0.057). CHROMagar identified several Candida species, and confirmation was made using API 20C AUX strips. One patient was lost to follow-up. Of 19 Molloplast-B samples, 7 had no growth, 4 grew C. albicans, 3 grew C. parapsilosis, 2 grew C. glabrata, 1 grew C. tropicalis, 2 grew a Trichosporon spp., and 2 grew a nonidentifiable colony. The analogous counts for 19 MPDS-SL samples were 10, 4, 1, 3, 0, 1, and 1 (p = 0.45 for culture positively, exact McNemar test). CONCLUSIONS: Candida growth on Molloplast-B was not significantly different from growth on MPDS-SL. Several yeast species were cultured from each material. The rates of culture-positive testing did not differ between the 2 resilient denture liners.

Adult↗

Relationship between salivary flow rates and Candida albicans counts.

Seventy-one persons (48 women, 23 men; mean age, 51.76 years) were evaluated for salivary flow rates and Candida albicans counts. Each person was seen on three different occasions. Samples of unstimulated whole, chewing-stimulated whole, acid-stimulated parotid, and candy-stimulated parotid saliva were collected under standardized conditions. An oral rinse was also obtained and evaluated for Candida albicans counts. Unstimulated and chewing-stimulated whole flow rates were negatively and significantly (p < 0.001) related to the Candida counts. Unstimulated whole saliva significantly (p < 0.05) differed in persons with Candida counts of 0 versus <500 versus < or = 500. Chewing-stimulated saliva was significantly (p < 0.05) different in persons with 0 counts compared with those with a > or = 500 count. Differences in stimulated parotid flow rates were not significant among different levels of Candida counts. The results of this study reveal that whole saliva is a better predictor than parotid saliva in identification of persons with high Candida albicans counts.

Analysis of Variance↗

Oral Candida in HIV-infected heterosexuals and intravenous drug users in Thailand.

The objectives of this study were to determine levels of oral yeasts in Thai people at different stages of HIV infection compared with HIV-negative controls, to identify factors associated with the levels of oral Candida, and to determine whether the levels of the organism can be used as a predictive clinical marker in HIV-infected individuals. One hundred and eighty HIV-infected heterosexual persons and intravenous drug users (IVDUs) were enrolled (152 men, 28 women). Eighty-three HIV-free subjects from the same population were included as controls (48 men, 35 women). Oral yeasts were isolated in 103 HIV-infected subjects (57.2%) and 36 HIV-negative controls (43.3%). The mean number of colony forming units (CFU) of oral Candida in the first group was 1.9x10(4) CFU/ml (range 2.2x10(2)-4.0x10(6) CFU/ml), which was significantly different statistically when compared with 1.7x10(3) CFU/ml (range 4.0x10(2)-1.2x10(5) CFU/ml) in the control group (P=0.0000). The following factors are significantly associated statistically with the levels of oral Candida among the subjects (P<0.05): age, stage of HIV infection, total number of lymphocyte cell count, risk group, nutritional status, general health status, weight loss, type of oral lesions and number of oral lesions and number of sites affected. The study revealed that HIV serostatus, stage of HIV infection, and the occurrence of oral lesions among HIV-infected subjects may be predicted by the levels of oral Candida (P<0.05). By using a cut-off point of 2.0x10(3) CFU/ml, the sensitivity and predicitve values of the level of oral Candida on the HIV serostatus was higher than that based on the culture positivity results alone, although the specificity was similar. These findings suggest that, in conjunction with some other clinical signs and laboratory findings, the levels of oral Candida may be used as a predictive marker of disease in HIV infection.

AIDS-Related Opportunistic Infections↗

Antifungal activity of propolis on different species of Candida.

Propolis is a resinous material collected by bees from the buds or other parts of plants. It is known for its biological properties, having antibacterial, antifungal and healing properties. The antifungal activity of propolis was studied in sensitivity tests on 80 strains of Candida yeasts: 20 strains of Candida albicans, 20 strains of Candida tropicalis, 20 strains of Candida krusei and 15 strains of Candida guilliermondii. The yeasts showed a clear antifungal activity with the following order of sensitivity: C. albicans > C. tropicalis > C. krusei > C. guilliermondii. Patients with full dentures who used a hydroalcoholic propolis extract showed a decrease in the number of Candida.

Antifungal Agents↗

[Candida infections in intensive care patients].

In 31 of 60 long-term ventilated intensive-care patients, a significant Candida antigen titer in serum was found that correlated with positive Candida cultures. In some cases the detection of the antigen was the first indication of Candida infection, while the isolation of the infectious agent required a culture period of 24-48 hours. In addition to routinely performed controls of Candida colonisation, determination of Candida antigen in the serum appears to be a valuable tool in the early diagnosis of candida infections.

Antigens, Fungal↗

Candida albicans strains heterozygous and homozygous for mutations in mitogen-activated protein kinase signaling components have defects in hyphal development.

The Candida albicans genes, CST20 and HST7, were cloned by their ability to suppress the mating defects of Saccharomyces cerevisiae mutants in the ste20 and ste7 genes, which code for elements of the mating mitogenactivated protein (MAP) kinase pathway. These Candida genes are both structural and functional homologs of the cognate Saccharomyces genes. The pattern of suppression in Saccharomyces is related to their presumptive position in the MAP kinase cascade. Null alleles of these genes were constructed in Candida. The Candida homozygous null mutants are defective in hyphal formation on some media, but are still induced to form hyphae by serum, showing that serum induction of hyphae is independent of the MAP kinase cascade. The Candida heterozygotes CST20/cst20 and HST7/hst7 are also defective in hyphal formation. This lack of dominance of the wild-type allele suggests that gene dosage is important in Candida.

Amino Acid Sequence↗

Influence of gastric colonization with Candida albicans on ulcer healing in rats: effect of ranitidine, aspirin and probiotic therapy.

OBJECTIVE: Candida albicans frequently inhabits the gastrointestinal tract of humans leading to gastrointestinal candidiasis, especially following suppression of gastric acidity, but studies on the relation between this fungal infection and gastric pathology are limited due to lack of convenient animal models resembling Candida infection in humans. MATERIAL AND METHODS. We compared the effects of C. albicans and vehicle inoculation on gastric secretion and healing of gastric ulcers induced by acetic acid in rats treated with 1) ranitidine (30 mg kg(-1) day(-1) s.c.) and 2) aspirin (ASA) (60 mg kg(-1) day(-1) i.g.) with or without probiotic bacteria Lactobacillus acidophillus. At day 0 and at 4, 15 and 25 days after ulcer induction, the ulcer area, the gastric blood flow (GBF), the quantitative gastric cultures of Candida and the expression of mRNAs for pro-inflammatory cytokines IL-1beta and TNF-alpha and growth factors EGF and TGFalpha were assessed in the gastric mucosa. RESULTS: Gastric acid output was reduced by over 40% soon after Candida inoculation and this effect persisted during all time intervals tested. The area of ulcers in control rats significantly decreased at day 15 and the ulcers disappeared almost completely after 25 days of their induction. In contrast, the ulcers were present until day 25 in Candida-inoculated rats followed by a fall in GBF and a rise in plasma gastrin levels, these effects being significantly attenuated by the co-treatment with Lactobacillus. Candidiasis was accompanied by up-regulation of mRNA for IL-1beta, TNF-alpha, EGF and TGFalpha and a significant increment in plasma IL-1beta and TNF-alpha levels. CONCLUSIONS: 1) Persistent colonization with Candida could be achieved in rats treated with antisecretory agents or non-steroidal anti-inflammatory drugs (NSAIDs) such as ASA; 2) candidiasis reduces gastric acid secretion, while delaying ulcer healing possibly due to the impairment in GBF in the ulcer area and enhanced expression and release of IL-1beta and TNFalpha and 3) probiotic therapy could be useful in the treatment against the deleterious action of fungal infection on the healing of pre-existing gastric ulcers.

Animals↗

Distribution and antifungal susceptibility of Candida species isolated from different age populations in Taiwan.

A total of 3,926 yeast isolates were isolated from 24 hospitals participating in the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) from July to September 2002. Candida albicans (69.1%) was the most common species, followed by Candida tropicalis (12.9%), Candida glabrata (8.3%), Candida parapsilosis (2.7%), Candida krusei (0.6%), and others (6.4%). To study the distribution and antifungal susceptibility of Candida species according to sources and patient ages, we have collected and analyzed the clinical data of 861 isolates. Of those 861 isolates, urine was the most common source (40%) followed by sputum (22.1%), blood (13.5%), central venous catheter (5.5%), wound (5.2%), and others (13.7%). With increasing age, we observed a significant increase in the percentage of isolates from urine (P=0.00005) and a parallel reduction from blood (P=0.009). As expected, more elder patients were hospitalized than younger ones (P=0.05). In total, 2.7% and 1.9% of isolates were resistant to amphotericin B and fluconazole, respectively. Antifungal susceptibilities of isolates from different age groups were not significantly different.

Adolescent↗

High rate of vaginal infections caused by non-C. albicans Candida species among asymptomatic women.

A prospective observational study of patients attending a gynecological clinic and those referred to a clinic for genitourinary infections was undertaken with the purpose of evaluating the relative prevalence of non-C. albicans Candida species among Candida isolates from the vagina in different clinical settings in an area with high occurrence of vulvovaginal candidiasis. The rate of non-C. albicans Candida species was 44.5% among asymptomatic women, 19.4% among those with sporadic vaginitis and 21% among patients with chronic vaginal symptoms (p < 0.001 for asymptomatic vs. pooled symptomatic women). No increase in the rate of non-C. albicans Candida was observed during a period of 4 years (1995-1998) despite a 1.57-fold increase in the sales of azole antifungal agents. Unlike some previous reports we could not document an association of non-C. albicans Candida species with chronic vaginal symptoms or increased use of azole antifungal agents. The significantly higher rate of these yeasts in asymptomatic women is in accord with the known tendency of non-C. albicans Candida species to cause mild symptoms.

Antifungal Agents↗

Macrophage microbicidal activity. Correlation between phagocytosis-associated oxidative metabolism and the killing of Candida by macrophages.

The mechanisms by which macrophages kill ingested microorganisms were explored using Candida albicans and Candida parapsilosis. The results indicate that efficient macrophage candidacidal activity depends upon the generation of oxygen metabolites by the phagocytic cell: (a) peritoneal macrophages from mice infected with bacillus Calmette-Guerin (BCG) or injected intraperitoneally with lipopolysaccharide (LPS) released more superoxide anion (0(2)(-)) during phagocytosis of candida and killed candida better than did resident macrophages; (b) cells of the macrophage-like line J774.1, which released negligible amounts of O(2)(-), could ingest the candida normally but not kill them; (c) killing of candida by resident, LPS- elicited, and BCG-activated macrophages was inhibited by agents that scavenge O(2)(-), hydrogen peroxide (H(2)0(2)), hydroxyl radical (x OH), and singlet oxygen; and (d) all three macrophage types killed C. parapsilosis more effectively than C. albicans, and (7. parapsilosis stimulated a more prompt and vigorous burst of macrophage oxygen consumption and 0(2)(-) release than did C. albicans. Macrophages ingested C. parapsilosis slightly more quickly than C. albicans, but phagocytosis of both strains was equivalent by 60 min of incubation. Although C. albicans contained higher concentrations of the oxygen-metabolite scavengers superoxide dismutase and catalase, neither fungal species scavenged 0(2)(-) or H(2)0(2) effectively; and C. albicans was killed more easily than C. parapsilosis by a xanthine oxidase system that generates primarily H(2)O(2) at pH 7, or 0(2)(-) and x OH at pH 10. Thus, the decreased killing of C. albicans appears to result primarily from the capability of this species to elicit less vigorous stimulation of macrophage oxidative metabolism. This capability may have general relevance to the pathogenicity of microorganisms.

Animals↗

Evolution of antifungal susceptibility among Candida species isolates recovered from human immunodeficiency virus-infected women receiving fluconazole prophylaxis.

The effect of fluconazole on the susceptibility of Candida isolates recovered from women infected with human immunodeficiency virus (HIV) was evaluated in a randomized, double-blind, placebo-controlled trial. Women with CD4(+) cell counts of < or =300 cells/mm(3) received either fluconazole (200 mg/week) or placebo as prophylaxis. The antifungal susceptibility of specimens was evaluated. One patient who received fluconazole and 2 patients assigned to placebo had Candida albicans isolates recovered that were resistant to fluconazole (MIC, > or =64 microg/mL). Eleven patients assigned fluconazole and 4 patients assigned placebo had non-albicans Candida strains (all Candida glabrata) recovered that were resistant to fluconazole. There was significant azole cross-resistance among the non-albicans Candida species isolates. Although the rate of azole resistance did not significantly increase after fluconazole prophylaxis, there was a trend toward more in vitro azole resistance in C. glabrata isolates from patients assigned fluconazole. Moreover, the majority of resistant vaginal isolates of Candida species were recovered after initiation of open-label fluconazole use.

AIDS-Related Opportunistic Infections↗