Yee-Chun Chen

Candida albicans Als1p: an adhesin that is a downstream effector of the EFG1 filamentation pathway.

Filamentation and adherence to host cells are critical virulence factors of Candida albicans. Multiple filamentation regulatory pathways have been discovered in C. albicans using Saccharomyces cerevisiae as a model. In S. cerevisiae, these pathways converge on Flo11p, which functions as a downstream effector of filamentation and also mediates cell–cell adherence (flocculation). In C. albicans, such effector(s) have not yet been identified. Here, we demonstrate that the cell surface protein Als1p is an effector of filamentation in C. albicans. We show that Als1p expression is controlled by the transcription factor Efg1p, which is known to be a key regulator of filamentation in C. albicans. Further, disruption of ALS1 inhibited filamentation, and autonomous expression of Als1p restored filamentation in an efg1 homozygous null mutant. Thus, Als1p functions as a downstream effector of the EFG1 filamentation pathway. In addition, we found that Als1p mediates both flocculation and adherence of C. albicans to endothelial cells in vitro. As a cell surface glycoprotein that mediates filamentation and adherence, Als1p has both structural and functional similarity to S. cerevisiae Flo11p. Consistent with our in vitro results, Als1p was required for both normal filamentation and virulence in the mouse model of haematogenously disseminated candidiasis.

Comparison of Both Clinical Features and Mortality Risk Associated with Bacteremia due to Community-Acquired Methicillin-Resistant Staphylococcus aureus and Methicillin-Susceptible S. aureus

BACKGROUND The majority of research about community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection has focused on skin and soft-tissue infections. No literature has been published on the clinical features and outcomes of adult patients with CA-MRSA bacteremia in comparison with patients with community-acquired methicillin-susceptible S. aureus (CA-MSSA) bacteremia. METHODS From 1 January 2001 through 31 December 2006, the demographic data and outcome of 215 consecutive adult patients admitted to a tertiary care center in Taiwan with S. aureus bacteremia (age, >16 years) who fulfilled the criteria for community-acquired S. aureus bacteremia were collected for analysis. RESULTS The mean age (+/-SD) was 56.8+/-20.5 years. There were 30 patients (14%) with CA-MRSA bacteremia and 185 (86%) patients with CA-MSSA bacteremia. Cutaneous abscess (odds ratio, 5.46; 95% confidence interval, 1.66-17.94) and necrotizing pneumonia (odds ratio, 24.81; 95% confidence interval, 2.63-234.03) were the independent predictors of CA-MRSA bacteremia; endovascular infection was the only independent predictor of CA-MSSA bacteremia. After Cox regression analysis, the independent significant risk factors for 30-day mortality included increased age, shock, and thrombocytopenia (<100,000 cells/microL). After adjustment, the day 30 mortality of patients with CA-MRSA bacteremia was not significantly higher than that of patients with CA-MSSA bacteremia (adjusted hazard ratio, 1.01; 95% confidence interval, 0.30-3.39; P = .986). Most (92%) of 25 available CA-MRSA isolates were multilocus sequence typing 59. CONCLUSIONS The number of adult patients with CA-MRSA bacteremia increased with time, and the disease was associated with more necrotizing pneumonia and cutaneous abscess but less endovascular infection than was CA-MSSA bacteremia. Patients with CA-MRSA bacteremia did not have higher mortality than did patients with CA-MSSA, even though most of the patients with CA-MRSA bacteremia did not receive empirical glycopeptide therapy.

Arsenic trioxide sensitivity is associated with low level of glutathione in cancer cells

Arsenic trioxide (As2O3) is a novel anticancer agent, which has been found to induce remission in acute promyelocytic leukaemic patients following daily intravenous administration. The therapeutic value of As2O3 in other cancers is still largely unknown. Cytotoxic tests in a panel of cancer cell lines showed that bladder cancer, acute promyelocytic leukaemic and gastrointestinal cancer cells were the most sensitive to As2O3 among 17 cell lines tested. Cellular glutathione (GSH) system plays an important role in arsenic detoxification in mammalian cells. Cancer cells that were intrinsically sensitive to As2O3 contained lower levels of GSH, whereas resistant cancer cells contained higher levels of GSH. On the other hand, there was no association of glutathione-S-transferase-π or multidrug resistance-associated protein 1 levels with arsenic sensitivity in these cancer cells. Multidrug-resistant cancer cells that were cross-resistant to arsenic contained higher levels of GSH or multidrug-resistance-associated protein 1 than their drug-sensitive parental cells. Cancer cells become more sensitive to arsenic after depletion of cellular GSH with L-buthionine sulphoximine. We concluded that cellular GSH level is the most important determinant of arsenic sensitivity in cancer cells. Cellular GSH level and its modulation by buthionine sulphoximine should be considered in designing clinical trials using arsenic in solid tumours.

Influence of Genospecies of Acinetobacter baumannii Complex on Clinical Outcomes of Patients with Acinetobacter Bacteremia

BACKGROUND acinetobacter baumannii complex infections are increasing in prevalence and are associated with a high mortality. Biochemical classification tests cannot differentiate A. baumannii (genospecies 2) from other genospecies. Genospecies typing offers a potential tool to determine whether there are major differences in pathogenicity among the genospecies. METHODS adult patients with A. baumannii complex bacteremia in intensive care units were prospectively observed from January 2007 through July 2009. A. baumannii complex was identified by biochemical methods and the Phoenix bacterial identification system. Genospecies were identified by 16S-23S ribosomal RNA intergenic-spacer sequencing. RESULTS among the 135 patients with A. baumannii complex bacteremia, 87 (64.4%) had isolates that belonged to genospecies 2, 36 (26.7%) had isolates that belonged to genospecies 13TU, and 12 (8.9%) had isolates that belonged to genospecies 3. Patients with A. baumannii (genospecies 2) bacteremia were more likely to have pneumonia than were patients with bacteremia due to genospecies 13TU (63.2 % vs 27.8%; P =.001), whereas patients with bacteremia due to genospecies 13TU were more likely to have primary bacteremia (69.4% vs 20.7%; P <.001). Genospecies 2 was less susceptible to antibiotics than were other genospecies. It was associated with a higher rate of mortality than was genospecies 13TU (58.6% vs 16.7%; P < .001). On multivariate analysis, genospecies 2 was an independent predictor of mortality (odds ratio, 5.46; 95% confidence interval, 2.00-14.91; P = .001). CONCLUSIONS genospecies 2 of the A. baumannii complex was associated with greater resistance to antibiotics and higher mortality among bacteremic patients, compared with other genospecies, especially genospecies 13TU. These findings emphasize the need to focus on genospecies to better understand the pathogenesis and epidemiology of infections caused by the A. baumannii complex.

Secular trends in the epidemiology of nosocomial fungal infections at a teaching hospital in Taiwan, 1981 to 1993.

OBJECTIVE To describe the incidence and patterns of nosocomial fungal infection in a large teaching hospital in Taiwan. DESIGN Prospective, hospitalwide nosocomial surveillance data from 1981 through 1993 were analyzed to show the secular trend in nosocomial fungal infection rates and to identify the most common pathogens and sites of infection (other than skin) in this hospital. SETTING AND PATIENTS The National Taiwan University Hospital is a medical school-affiliated hospital in the city of Taipei, Taiwan, with a 1200-bed capacity before 1991 and 1500 beds since 1992. It provides both primary and tertiary medical care. RESULTS The overall nosocomial fungal infection rate rose from 0.9 infections per 1000 discharges in 1981 to 6.6 per 1000 discharges in 1993, with the highest rate at the medical intensive-care unit (26.5/1000 discharges in 1993). This increase in infection rate was found at four major anatomic sites of infection, particularly including the bloodstream (0.08-2.19/1000 discharges) and the urinary tract (0.36-2.95/1000 discharges). Of 256 pathogens causing nosocomial fungemia from 1981 through 1993, Candida albicans was the most commonly isolated (50.8%), followed by Candida tropicalis (17.6%). Candida parapsilosis (11.7%), and Candida glabrata (8.2%). As compared to isolates from 1981 through 1988, the proportion of C parapsilosis and C glabrata isolated between 1989 and 1993 increased more than sixfold and fourfold, respectively. The increasing importance of fungal infections was confirmed further by the increased use of amphotericin B and azoles in this hospital. CONCLUSIONS Candida species and other yeasts have become a prominent cause of nosocomial infections in this hospital. These fungal pathogens accounted for a higher proportion of nosocomial bloodstream and urinary infections than any single bacterial species. Therefore, it is important to conduct a prospective epidemiological study and to establish in vitro antifungal susceptibility testing to enhance efforts to control nosocomial fungal infections and to minimize the risk of emergence of antifungal resistance.

Malignancies associated with dermatomyositis and polymyositis in Taiwan: a nationwide population-based study

Background  Previous studies showed that idiopathic inflammatory myopathies (IIM) carried an increased risk of cancers. However, no large‐scale study of IIM has been conducted in the Chinese population.

SARS in Hospital Emergency Room

Thirty-one cases of severe acute respiratory syndrome (SARS) occurred after exposure in the emergency room at the National Taiwan University Hospital. The index patient was linked to an outbreak at a nearby municipal hospital. Three clusters were identified over a 3-week period. The first cluster (5 patients) and the second cluster (14 patients) occurred among patients, family members, and nursing aids. The third cluster (12 patients) occurred exclusively among healthcare workers. Six healthcare workers had close contact with SARS patients. Six others, with different working patterns, indicated that they did not have contact with a SARS patient. Environmental surveys found 9 of 119 samples of inanimate objects to be positive for SARS coronavirus RNA. These observations indicate that although transmission by direct contact with known SARS patients was responsible for most cases, environmental contamination with the SARS coronavirus may have lead to infection among healthcare workers without documented contact with known hospitalized SARS patients.

Longitudinal analysis of chlorhexidine susceptibilities of nosocomial methicillin-resistant Staphylococcus aureus isolates at a teaching hospital in Taiwan

BACKGROUND Chlorhexidine has been widely used for hand hygiene to prevent transmission of nosocomial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). However, data on longitudinal surveillance of the susceptibility of MRSA isolates to chlorhexidine are limited. METHODS A total of 240 nosocomial MRSA isolates obtained in 1990, 1995, 2000 and 2005 at National Taiwan University Hospital (NTUH), a hospital where chlorhexidine gluconate was used for hand hygiene for more than 20 years, were included in the study. Chlorhexidine susceptibility, molecular typing using multilocus sequence typing and distribution of the qacA/B gene of these MRSA isolates were studied. RESULTS The proportion of tested MRSA with a high MIC of chlorhexidine (>or=4 mg/L) was 1.7% in 1990, 50% in 1995, 40% in 2000 and 46.7% in 2005. Among these 83 isolates with high chlorhexidine MICs, 55.4% carried the qacA/B gene. MRSA isolates carrying the qacA/B gene were first detected in 1995 and belonged to a single clone at that time. However, the qacA/B gene was detected in MRSA isolates belonging to seven different clones in 2005. CONCLUSIONS The proportion of tested MRSA isolates with high chlorhexidine MICs at NTUH increased from 1990 to 1995 and remained steady thereafter. The presence of the qacA/B gene may contribute to the spread of specific MRSA clones.

Klebsiella pneumoniae isolates causing liver abscess in Taiwan

Klebsiella pneumoniae has been the leading cause of pyogenic liver abscess in Taiwan during the period from 1985 to 1999, which is different from other countries. The present study investigated the in vitro antimicrobial susceptibilities of 51 K. pneumoniae isolates collected from blood cultures of patients with liver abscess in Taiwan during the period from 1993-1997, and typed by pulsed-field gel electrophoresis (PFGE). All 51 isolates were resistant to ampicillin, but susceptible to other antimicrobial agents. The minimum inhibitory concentrations (MICs) were less than 1 microg/ml for the third- and fourth-generation cephalosporins, monobactam, carbapenems, and ciprofloxacin. In comparison, 62 isolates of K. pneumoniae from community-acquired bacteremic patients without liver abscess had similar antimicrobial susceptibilities, while 142 isolates from patients with hospital-acquired bacteremia without liver abscess were much less susceptible to all of the tested antimicrobial agents. PFGE molecular epidemiologic analysis found 20 out of 51 isolates belonged to eight clusters of genetically related strains, with two or three isolates in each clusters. The other 31 isolates were genetically distinct strains. This study demonstrated that K. pneumoniae isolates which cause liver abscess in Taiwan remained susceptible to a wide range of antimicrobial agents and that they were not genetically related.

Effectiveness and Limitations of Hand Hygiene Promotion on Decreasing Healthcare–Associated Infections

Background Limited data describe the sustained impact of hand hygiene programs (HHPs) implemented in teaching hospitals, where the burden of healthcare-associated infections (HAIs) is high. We use a quasi-experimental, before and after, study design with prospective hospital-wide surveillance of HAIs to assess the cost effectiveness of HHPs. Methods and Findings A 4-year hospital-wide HHP, with particular emphasis on using an alcohol-based hand rub, was implemented in April 2004 at a 2,200-bed teaching hospital in Taiwan. Compliance was measured by direct observation and the use of hand rub products. Poisson regression analyses were employed to evaluate the densities and trends of HAIs during the preintervention (January 1999 to March 2004) and intervention (April 2004 to December 2007) periods. The economic impact was estimated based on a case-control study in Taiwan. We observed 8,420 opportunities for hand hygiene during the study period. Compliance improved from 43.3% in April 2004 to 95.6% in 2007 (p<.001), and was closely correlated with increased consumption of the alcohol-based hand rub (r = 0.9399). The disease severity score (Charlson comorbidity index) increased (p = .002) during the intervention period. Nevertheless, we observed an 8.9% decrease in HAIs and a decline in the occurrence of bloodstream, methicillin-resistant Staphylococcus aureus, extensively drug-resistant Acinetobacter baumannii, and intensive care unit infections. The intervention had no discernable impact on HAI rates in the hematology/oncology wards. The net benefit of the HHP was US