Browsing by Author "Lo, HJ"

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CaNdt80 is involved in drug resistance in Candida albicans by regulating CDR1
(2004-12-01)
Chen, CG
;
Yang, YL
;
Shih, HI
;
Su, CL
;
Lo, HJ
Overexpression of CDR1, an efflux pump, is one of the major mechanisms contributing to drug resistance in Candida albicans. CDR1 p-lacZ was constructed and transformed into a Saccharomyces cerevisiae strain so that the lacZ gene could be used as the reporter to monitor the activity of the CDR1 promoter. Overexpression of CaNDT80, the C albicans homolog of S. cerevisiae NDT80, increases the beta-galactosidase activity of the CDR1 p-lacZ construct in S. cerevisiae. Furthermore, mutations in CaNDT80 abolish the induction of CDR1 expression by antifungal agents in C albicans. Consistently, the Candt80/Candt80 mutant is also more susceptible to antifungal drugs than the wild-type strain. Thus, the gene for CaNdt80 may be the first gene among the regulatory factors involved in drug resistance in C. albicans whose function has been identified.
Colonization of human immunodeficiency virus-infected outpatients in Taiwan with Candida species
(2005-04-01)
Hung, CC
;
Yang, YL
;
Lauderdale, TL
;
McDonald, LC
;
Hsiao, CF
To understand the Candida colonization of human immunodeficiency virus (HIV)-infected outpatients in Taiwan, we have conducted a prospective cohort study of Candida colonization and its risk factors at the National Taiwan University Hospital from 1999 to 2002. More than 50% of the patients were colonized with Candida species, and 12% developed symptomatic candidiasis. Patients colonized with fluconazole-resistant strains of Candida species had a higher prevalence of candidiasis than those colonized with susceptible strains. Our analysis found that antibiotic treatment and lower CD4(+) counts (< 200 cells/mm(3)) increased the rate of oropharyngeal candidiasis in HIV-infected patients, while antiretroviral therapy protected patients from the development of candidiasis.
Distribution and antifungal susceptibility of Candida species causing candidemia from 1996 to 1999
(2004-01-01)
Cheng, MF
;
Yu, KW
;
Tang, RB
;
Fan, YH
;
Yang, YL
Susceptibilities to amphotericin B and fluconazole of 383 Candida species isolated from blood were determined. Candida albicans was the most common species (55.6%), followed by Candida parapsilosis (17.5%), Candida tropicalis (16.5%), Candida glabrata (5.2%), Candida guilliermondii (2.3%), and others (2.9%). All but three isolates, Candida ciferrii, C. tropicalis, and C glabrata, one each, were susceptible to amphotericin B. A total of 367 (95.8%) and 15 (4.2%) isolates were susceptible and susceptible-dose dependent to fluconazole, respectively. Only one isolate, a C glabrata, was resistant to fluconazole. Few patients (13%) having prior fluconazole treatments may explain the low rate of resistance to fluconazole in this study. (C) 2004 Elsevier Inc. All rights reserved.
Distribution and susceptibility to amphotericin B and fluconazole of Candida spp. isolated from Taiwan
(2005-04-01)
Yang, YL
;
Ho, YA
;
Cheng, HH
;
Lo, HJ
;
生物科技學系
Susceptibilities to amphotericin B and fluconazole of 628 clinical yeast strains collected from 22 hospitals in Taiwan were determined. A total of 53 isolates (8.4%) were resistant to fluconazole. Each hospital had different resistance rate to fluconazole ranging from 0 % to 24 %. None of the 186 isolates from eight of the 22 hospitals was resistant to fluconazole. In contrast, isolates from nine of the remaining 14 hospitals had greater than 10 % resistance rate to fluconazole. Consistently, 88.9 % (8/9) fluconazole-resistant C. albicans isolates were from hospitals having a high resistance rate to fluconazole. The prevalence of various Candida spp. in each hospital was different. A positive association was found between the prevalence of C. tropicalis and the resistance rate to fluconazole for individual hospitals. Although only three isolates (0.5 %) were resistant to amphotericin B, a co-resistance to both amphotericin B and fluconazole was observed, which highlights the emerging problem of drug resistance.
Effect of prolonged HAART on oral colonization with Candida and candidiasis
(2006-01-20)
Yang, YL
;
Lo, HJ
;
Hung, CC
;
Li, YC
;
生物科技學系
Background: Progressive cell-mediated immunodeficiency with decrease of CD4+ lymphocyte count to less than or equal to 200 cells/mm(3) is a major risk factor for colonization with Candida species and development of candidiasis. Oropharyngeal candidiasis may occur in up to 90% of human immunodeficiency virus (HIV)-infected patients during the course of the disease. This study is to determine the effect of prolonged highly active antiretroviral therapy (HAART) on oropharyngeal colonization with Candida species and oral candidiasis. Methods: A prospective, longitudinal follow-up study in HIV-infected patients receiving HAART. Results: The mean CD4+ count increased from 232.5 to 316 cells/mm(3) and the proportion of patients whose CD4+ count less than 200 cells/mm(3) decreased from 50.0% to 28.9% (p = 0.0003) in patients receiving HAART for at least 2 years. The prevalence of oral candidiasis decreased from 10.6% to 2.1% (p = 0.004). The decrease in Candida colonization was less impressive, falling from 57.8% to 46.5% (p = 0.06). Of the 142 patients enrolled in at least two surveys, 48 (33.8%) remained colonized with Candida and 42 (29.6%) remained negative. In the remaining 52 patients, 34 switched from culture positive to negative, and an increase in CD4+ lymphocytes was noted in 91.2% of them. Among the 18 patients who switched from culture negative to positive, 61.1% also demonstrated an increase in CD4+ lymphocyte count (p = 0.01). Conclusion: These findings indicate that HAART is highly effective in decreasing oral candidiasis in association with a rise in CD4+ lymphocyte counts, but only marginally effective in eliminating Candida from the oropharynx.
Efg1 involved in drug resistance by regulating the expression of ERG3 in Candida albicans
(2005-03-01)
Lo, HJ
;
Wang, JS
;
Lin, CY
;
Chen, CG
;
Hsiao, TY
The ERG3 gene in Candida albicans was identified as a gene whose mRNA level was higher in the cph1/cph1 efg1/efg1 double mutant than in the wild-type cells. Further study showed that Efg1, but not Cph1, negatively regulated ERG3. Mutations in EFG1 consistently increased the susceptibility of the cells to antifungal agents.
Identification of trans-regulatory factors of the efflux pumps involved in drug resistance in Candida albicans.
(2003-07-01)
Chen, CG
;
Shih, HI
;
Yang, YL
;
Lo, HJ
;
生物科技學系
In vitro activity of voriconazole against Candida species isolated in Taiwan
(2004-09-01)
Yang, YL
;
Cheng, HH
;
Lo, HJ
;
生物科技學系
;
Department of Biological Science and Technology
The activity of voriconazole was determined against 285 Candida species consisting of 53 resistant isolates, 43 susceptible-dose dependent and 189 isolates susceptible to fluconazole. The MIC50 and MIC90 to fluconazole were 8 and 64 mg/l, respectively. The range of minimum inhibitory concentrations (MICs) to voriconazole was from 0.0325 to 2 mg/l and the MIC50 and MIC90 were 0.125 and 0.5 mgA, respectively. Only 3 of 285 tested isolates had MICs to voriconazole equal to 2 mg/l. A total of 38 isolates, consisted of 3 Candida albicans, 5 Candida krusei, 7 Candida tropicalis and 21 Candida glabrata, had MICs greater than or equal to 0.5 mg/l to voriconazole. There was correlation between the susceptibility to fluconazole and voriconazole. (C) 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Molecular epidemiology of long-term colonization of Candida albicans strains from HIV-infected patients
(2006-04-01)
Li, SY
;
Yang, YL
;
Chen, KW
;
Cheng, HH
;
Chiou, CS
Twenty-one Candida albicans isolates from three HIV-infected patients were collected over a period of 3 years and characterized for fluconazole susceptibility, infectivity and genetic relatedness. Fluconazole resistance was found in five isolates, four exhibited dose-dependent susceptibility and the remainder were fully susceptible to this agent. Pulsed-field gel clectrophoresis of SfiI restriction digests of the genomic DNA from the isolates revealed that isolates from the same swab specimen were identical despite differences in Susceptibility to fluconazole and isolates recovered over time from the three patients retained clonally related DNA fingerprints within each patient. This small-scale study confirms the persistence of oral colonization of C. albicans strains in HIV-infected patients. Clinical data also suggests that the primary infecting strain may become a persistent colonist in the oral cavity once the immune function of the patient has been restored.
Risk factors for fatal candidemia caused by Candida albicans and non-albicans Candida species
(2005-04-07)
Cheng, MF
;
Yang, YL
;
Yao, TJ
;
Lin, CY
;
Liu, JS
Background: Invasive fungal infections, such as candidemia, caused by Candida species have been increasing. Candidemia is not only associated with a high mortality (30% to 40%) but also extends the length of hospital stay and increases the costs of medical care. Sepsis caused by Candida species is clinically indistinguishable from bacterial infections. Although, the clinical presentations of the patients with candidemia caused by Candida albicans and non-albicans Candida species (NAC) are indistinguishable, the susceptibilities to antifungal agents of these species are different. In this study, we attempted to identify the risk factors for candidemia caused by C. albicans and NAC in the hope that this may guide initial empiric therapy. Methods: A retrospective chart review was conducted during 1996 to 1999 at the Veterans General Hospital-Taipei. Results: There were 130 fatal cases of candidemia, including 68 patients with C. albicans and 62 with NAC. Candidemia was the most likely cause of death in 55 of the 130 patients (42.3%). There was no significant difference in the distribution of Candida species between those died of candidemia and those died of underlying conditions. Patients who had one of the following conditions were more likely to have C. albicans, age >= 65 years, immunosuppression accounted to prior use of steroids, leukocytosis, in the intensive care unit (ICU), and intravascular and urinary catheters. Patients who had undergone cancer chemotherapy often appeared less critically ill and were more likely to have NAC. Conclusion: Clinical and epidemiological differences in the risk factors between candidemia caused by C. albicans and NAC may provide helpful clues to initiate empiric therapy for patients infected with C. albicans versus NAC.
Susceptibilities of Candida species to amphotericin B and fluconazole: The emergence of fluconazole resistance in Candida tropicalis
(2004-01-01)
Yang, YL
;
Ho, YA
;
Cheng, HH
;
Ho, M
;
Lo, HJ
OBJECTIVE: To determine the susceptibilities of Candida species isolated from Taiwan to amphotericin B and fluconazole. DESIGN: Prospective surveillance study. METHODS: Each hospital was asked to submit up to 10 C. albicans and 40 non-albicans Candida species during the collection period, from April 15 to June 15, 1999. One isolate was accepted from each episode of infection. The broth microdilution method was used to determine susceptibilities to amphotericin B and fluconazole. RESULTS: Only 3 of 632 isolates, one each of C. famata, C. krusei, and C. tropicalis, were resistant to amphotericin B. A total of 53 (8.4%) of 632 clinical yeast isolates, consisting of 4% C. albicans, 8% C. glabrata, 15% C. tropicalis, and 70% C. krusei, were resistant to floconnzole. In contrast. no C. Parapsilosis isolate was resistant to fluconazole. Isolates from tertiary-care medical centers had higher rates of resistance to fluconazole than did those from regional and local hospitals (11.4% vs 6.6%). Isolates from different sources showed different levels of susceptibility to fluconazole. All of the isolates with the exception of C. tropicalis and C. krusei isolated from blood were susceptible to fluconazole. A pattern of co-resistance to both amphotericin B and fluconazole was observed. CONCLUSIONS: Non-albicans Candida species had higher rates of resistance to fluconazole than did C. albicans (44 of 395 [11.2%] vs 9 of 237 [3.8%]; P = .002). The increasing rate of fluconazole resistance in C. tropicalis (15%) is important because C. tropicalis is one of the most commonly isolated non-albicans Candida species.
Susceptibilities to amphotericin B and fluconazole of Candida species in TSARY 2002
(2005-03-01)
Yang, YL
;
Li, SY
;
Cheng, HH
;
Lo, HJ
;
生物科技學系
Susceptibilities to amphotericin B and fluconazole of 909 Candida species collected during the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) in 2002 were determined by the broth microdilution method. There were 395 (43.5%) Candida albicans, 244 (26.8%) C. tropicalis, 187 (20.6%) C. glabrata, 63 (6.9%) C. parapsilosis, 9 (1%) C. krusei, and 11 (1.2%) others. Among them, 23 (2.5%) isolates were resistant to amphotericin B. They consisted of 10 C. glabrata, 6 C. krusei, 3 C. albicans, 1 C. tropicalis, 1 C. parapsilosis, and 2 others. The resistance rate to amphotericin B has increased compared with that of TSARY 1999 (2.5% versus 0.5%). There were 7 C. krusei, 5 C. albicans, 3 C. glabrata, and 2 others isolates resistant to fluconazole. The resistance rate to fluconazole has decreased from 8.4% in 1999 to 1.9% in 2002. A pattern of coresistance to both amphotericin B and fluconazole was observed. (c) 2005 Elsevier Inc. All rights reserved.
The trend of susceptibilities to amphotericin B and fluconazole of Candida species from 1999 to 2002 in Taiwan
(2005-11-03)
Yang, YL
;
Li, SY
;
Cheng, HH
;
Lo, HJ
;
生物科技學系
Background: Candida species have various degrees of susceptibility to common antifungal drugs. The extent of resistance to amphotericin B and fluconazole of Candida glabrata isolates causing candidemia has been reported. Active surveillance may help us to monitor the trend of susceptibility to antifungal drugs and to determine if there is an emerging co-resistance to both drugs of Candida species, specifically, of C. glabrata in Taiwan. Methods: The susceptibilities to amphotericin B and fluconazole of Candida species collected in 1999 and 2002 of the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) were determined by the microdilution method. Results: The antifungal susceptibilities of 342 and 456 isolates collected from 11 hospitals participating in both TSARY 1999 and TSARY 2002, respectively, have been determined. The resistance rate to amphotericin B has increased from 0.3% in the TSARY1999 to 2.2% in the TSARY 2002. In contrast, the resistance rate to fluconazole has decreased from 8.8% to 2.2%. Nevertheless, significantly more C. glabrata isolates were not susceptible to fluconazole in the TSARY 2002 (47.4%) than that in the TSARY 1999 (20.8%). There were 9.8% and 11% of C. glabrata isolates having susceptible-dose dependent and resistant phenotype to fluconazole in the TSARY 1999, verse 45.3% and 2.1% in the TSARY 2002. Conclusion: There was an increase of resistance rate to amphotericin B in C. glabrata. On the other hand, although the resistance rate to fluconazole has decreased, almost half of C. glabrata isolates were not susceptible to this drug. Hence, continuous monitoring the emerging of coresistance to both amphotericin B and fluconazole of Candida species, specifically, of C. glabrata, will be an important early-warning system.