Relationship between the Number of Repeats in the Neck Regions of L-SIGN and Augmented Virus Replication and Immune Responses in Dengue Hemorrhagic Fever.

C-type lectins play a crucial role as pathogen-recognition receptors for the dengue virus, which is responsible for causing both dengue fever (DF) and dengue hemorrhagic fever (DHF). DHF is a serious illness caused by the dengue virus, which exists in four different serotypes: DEN-1, DEN-2, DEN-3, and DEN-4. We conducted a genetic association study, during a significant DEN-2 outbreak in southern Taiwan, to explore how variations in the neck-region length of L-SIGN (also known as CD209L, CD299, or CLEC4M) impact the severity of dengue infection. PCR genotyping was utilized to identify polymorphisms in variable-number tandem repeats. We constructed L-SIGN variants containing either 7- or 9-tandem repeats and transfected these constructs into K562 and U937 cells, and cytokine and chemokine levels were evaluated using enzyme-linked immunosorbent assays (ELISAs) following DEN-2 virus infection. The L-SIGN allele 9 was observed to correlate with a heightened risk of developing DHF. Subsequent results revealed that the 9-tandem repeat was linked to elevated viral load alongside predominant T-helper 2 (Th2) cell responses (IL-4 and IL-10) in K562 and U937 cells. Transfecting K562 cells in vitro with L-SIGN variants containing 7- and 9-tandem repeats confirmed that the 9-tandem repeat transfectants facilitated a higher dengue viral load accompanied by increased cytokine production (MCP-1, IL-6, and IL-8). Considering the higher prevalence of DHF and an increased frequency of the L-SIGN neck's 9-tandem repeat in the Taiwanese population, individuals with the 9-tandem repeat may necessitate more stringent protection against mosquito bites during dengue outbreaks in Taiwan.

Investigating the Current Status of SARS-CoV-2 Antibodies in Hospital Staff.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 had reported over 676 million cases by March 2023. The main aim of this study is to investigate whether the levels of anti-S and anti-N antibodies could precisely indicate the degree of protection against SARS-CoV-2 and affect the probability or time of contracting COVID-19. In this study, a serosurveillance study was conducted in healthcare workers (HCWs) at a regional hospital in Taiwan to evaluate their antibody levels based on infection and vaccination status. Of 245 HCWs enrolled, all have been vaccinated prior to infection. Of these, 85 participants were infected by SARS-CoV-2, while 160 participants were not infected at the time of blood sample collection. The level of anti-SARS-CoV-2 S antibody was significantly higher in the infected HCWs than in the non-infected participants (p < 0.001). It is worth noting that the mean duration between the administration of the last dose of the vaccine and the occurrence of SARS-CoV-2 infection was 5.61 ± 2.95 months. Our follow-up survey revealed that the non-infected group had significantly higher levels of antibodies compared to the infected group (all p < 0.001). In conclusion, this study suggests that the level of antibodies could serve as a reflection of the protective efficacy against SARS-CoV-2 infection. It has the implication for vaccine decision-making policies in the future.

Genetic relatedness among azole-resistant Candida tropicalis clinical strains in Taiwan from 2014 to 2018.

To monitor trends in the distribution of yeast species and the susceptibilities of these species to commonly prescribed antifungal drugs, we conduct the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) every 4 years. We found that 25 of 294 Candida tropicalis isolates from TSARY 2014 and 31 of 314 C. tropicalis isolates from TSARY 2018 were resistant to fluconazole. We determined the genetic relatedness among fluconazole-resistant C. tropicalis isolates by multilocus sequence typing (MLST). Among 174 C. tropicalis isolates, including all 56 fluconazole-resistant, all 26 susceptible-dose dependent and 92 selected fluconazole-susceptible isolates, 59 diploid sequence types (DSTs) were identified. We found that 22 of the 25 fluconazole-resistant C. tropicalis from TSARY 2014 and 29 of the 31 fluconazole-resistant C. tropicalis from TSARY 2018 were genetically related and belonged to the same cluster (clade 4). A combination of mutation and overexpression of ERG11, encoding the target of azole drugs, was the major mechanism contributing to drug resistance. Approximately two-thirds of reviewed patients infected or colonised by fluconazole-resistant C. tropicalis were azole-naïve. Furthermore, there was no evidence of patient-to-patient transmission. Because the clade 4 fluconazole-resistant C. tropicalis strain persists in Taiwan, it is important to identify the source of azole-resistant C. tropicalis to prevent the spread of this resistant strain.

Risk Factors of 30-Day All-Cause Mortality in Patients with Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infection.

An optimal antimicrobial regimen for the treatment of patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) is currently unavailable. This study aimed to identify the appropriate antibiotics and the risk factors of all-cause mortality for CRKP BSI patients. This retrospective cohort study included the hospitalized patients with CRKP BSI. Primary outcome was 30-day all-cause mortality. Cox regression analysis was used to evaluate the risk factors of 30-day mortality. A total of 89 patients were included with a 30-day mortality of 52.1%. A total of 52 (58.4%) patients were treated with appropriate antimicrobial regimens and 58 (65.2%) isolates carried blaKPC-2 genes. Microbiologic eradication within 7 days (adjusted hazard ratio [HR] = 0.09, p < 0.001), platelet count (per 1 × 104/mm3, adjusted HR = 0.95, p = 0.002), and Pitt bacteremia scores (adjusted HR = 1.40, p < 0.001) were independently associated with 30-day all-cause mortality. No effective antimicrobial regimens were identified. In conclusion, risk factors of 30-day mortality in patients with CRKP BSI included microbiologic eradication > 7 days, lower platelet count, and a higher Pitt bacteremia score. These findings render a new insight into the clinical landscape of CRKP BSI.

First COVID-19 mortality case in Taiwan with bacterial co-infection by national surveillance of critically ill patients with influenza-negative pneumonia.

A 63-year-old diabetic smoker with alcoholism was the first mortality case of coronavirus disease 2019 (COVID-19) in Taiwan. As concurrently infected with Klebsiella pneumoniae and subsequently with Klebsiella aerogenes, he was exposed by a national survey of patients with critically influenza-negative pneumonia. We recommend COVID-19 screening for patients with severe flu-like syndrome and protecting health-care workers from being infected.

The impact of global budgeting in Taiwan on inpatients with unexplained fever.

Unexplained fever is one of the most common and difficult diagnostic problems faced daily by clinicians. This study evaluated the differences in health service utilization, health care expenditures, and quality of care provided to patients with unexplained fever before and after global budget (GB) implementation in Taiwan.The National Health Insurance Research Database was used for analyzing the health care expenditures and quality of care before and after implementation of the GB system. Patients diagnosed as having unexplained fever during 2000-2001 were recruited; their 2000-2001 and 2004-2005 data were considered baseline and postintervention data, respectively.Data of 259 patients with unexplained fever were analyzed. The mean lengths of stay (LOSs) before and after GB system implementation were 4.22 ±â€Š0.35 days and 5.29 ±â€Š0.70 days, respectively. The mean costs of different health care expenditures before and after implementation of the GB system were as follows: the mean diagnostic, drug, therapy, and total costs increased respectively from New Taiwan Dollar (NT$) 1440.05 ±â€ŠNT$97.43, NT$3249.90 ±â€ŠNT$1108.27, NT$421.03 ±â€ŠNT$100.03, and NT$13,866.77 ±â€ŠNT$2,114.95 before GB system implementation to NT$2224.34 ±â€ŠNT$238.36, NT$4272.31 ±â€ŠNT$1466.90, NT$2217.03 ±â€ŠNT$672.20, and NT$22,856.41 ±â€ŠNT$4,196.28 after implementation. The mean rates of revisiting the emergency department within 3 days and readmission within 14 days increased respectively from 10.5% ±â€Š2.7% and 8.3% ±â€Š2.4% before implementation to 6.3% ±â€Š2.2% and 4.0% ±â€Š1.7% after implementation.GB significantly increased LOS and incremental total costs for patients with unexplained fever; but improved the quality of care.

The clinical management of cesarean section-acquired Mycobacterium abscessus surgical site infections.

INTRODUCTION: Rapidly growing mycobacteria (RGM) can cause a broad spectrum of both community and healthcare-associated infections in humans. The aim of this study was to report the clinical management and outcomes of successive patients following cesarean delivery with healthcare-associated surgical site infections (SSIs) caused by RGM. METHODOLOGY: Patients who were admitted to Chung Shan Medical University Hospital, Taichung, Taiwan, between September 2006 and July 2008, and who developed SSIs following cesarean delivery at an obstetrics hospital and were then referred to our hospital, were enrolled. Demographic characteristics of the patients and clinical isolates were obtained retrospectively and an environmental investigation was performed. PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of the hsp65gene and pulsed-field gel electrophoresis (PFGE) of large genomic DNA restriction fragments were applied to differentiate Mycobacterium species. RESULTS: Seventeen patients were diagnosed with RGM infections by microbiology and/or histopathology. Mycobacterial isolates by PCR-RFLP analysis from 15 patients revealed Mycobacterium abscessus (M. abscessus) and M. lentiflavum. Most of the patients received surgical debridement and combination antimicrobial therapy and were eventually cured. CONCLUSIONS: Our study demonstrates the potential that RGM infections have in causing healthcare-associated SSIs. Surgery plus prolonged combination antimicrobial therapy seemed to be an effective option for the management of M. abscessus infections.

Community-acquired urinary tract infection in kidney transplantation: risk factors for bacteremia and recurrent infection.

BACKGROUND/PURPOSE: Urinary tract infection (UTI) is the most common type of infectious complication among kidney transplant patients. However, the antibiotic susceptibility of causative microorganisms and risk factors for concomitant bacteremia and recurrent infection are rarely discussed. METHODS: This was a retrospective cohort review of kidney transplant recipients who had received follow-up in the past 10 years at the Chung-Shan Medical University (Taichung, Taiwan). Only community-acquired and symptomatic UTIs were included in this study. RESULTS: During the 53 ± 22 months of follow-up, 99 patients developed 167 episodes of UTI. Forty-two (25%) episodes had concomitant bacteremia. Escherichia coli was the most common causative microorganism, and strains with resistance to multiple commonly used empirical antibiotics began to emerge. The independent risk factors for UTI with concomitant bacteremia in multivariate analysis were immunosuppression with tacrolimus (adjusted odds ratio [AOR] 3.17; 95% confidence interval [CI] 1.29-7.75; P = 0.011) and baseline serum creatinine level >1.3 mg/dL before first UTI (AOR 2.55; 95% CI 1.02-6.36; P = 0.045). However, there were no factors that were significantly associated with recurrent infection. CONCLUSION: From this study, we found that E coli tends to have resistance to commonly used empirical antibiotics in this modern era and that patients who use the immunosuppressant tacrolimus and have baseline serum creatinine level >1.3 mg/dL before their first UTI have a tendency to suffer from concomitant bacteremia and even sepsis.

Assessment of hypermucoviscosity as a virulence factor for experimental Klebsiella pneumoniae infections: comparative virulence analysis with hypermucoviscosity-negative strain.

BACKGROUND: Klebsiella pneumoniae displaying the hypermucoviscosity (HV) phenotype are considered more virulent than HV-negative strains. Nevertheless, the emergence of tissue-abscesses-associated HV-negative isolates motivated us to re-evaluate the role of HV-phenotype. RESULTS: Instead of genetically manipulating the HV-phenotype of K. pneumoniae, we selected two clinically isolated K1 strains, 1112 (HV-positive) and 1084 (HV-negative), to avoid possible interference from defects in the capsule. These well-encapsulated strains with similar genetic backgrounds were used for comparative analysis of bacterial virulence in a pneumoniae or a liver abscess model generated in either naïve or diabetic mice. In the pneumonia model, the HV-positive strain 1112 proliferated to higher loads in the lungs and blood of naïve mice, but was less prone to disseminate into the blood of diabetic mice compared to the HV-negative strain 1084. In the liver abscess model, 1084 was as potent as 1112 in inducing liver abscesses in both the naïve and diabetic mice. The 1084-infected diabetic mice were more inclined to develop bacteremia and had a higher mortality rate than those infected by 1112. A mini-Tn5 mutant of 1112, isolated due to its loss of HV-phenotype, was avirulent to mice. CONCLUSION: These results indicate that the HV-phenotype is required for the virulence of the clinically isolated HV-positive strain 1112. The superior ability of the HV-negative stain 1084 over 1112 to cause bacteremia in diabetic mice suggests that factors other than the HV phenotype were required for the systemic dissemination of K. pneumoniae in an immunocompromised setting.

Antimicrobial resistance of bacterial isolates from respiratory care wards in Taiwan: a horizontal surveillance study comparison of the characteristics of nosocomial infection and antimicrobial-resistant bacteria in adult Intensive Care Units and two respiratory care facilities for mechanically ventilated patients at a tertiary care centre in Taiwan.

The objectives of this study were to compare the incidence of nosocomial infections (NIs) and the distribution of resistant nosocomial pathogens in adult Intensive Care Units (ICUs) and two respiratory care facilities for prolonged mechanically ventilated patients [i.e. the respiratory care centre (RCC) and the respiratory care ward (RCW)] in a 1100-bed tertiary care hospital in Taiwan from 2003 to 2006. The overall incidences of NI for adult ICUs, the RCC and the RCW were 14.0, 10.3 and 5.0 per 1000 patient-days, respectively. Urinary tract infections, bloodstream infections and pneumonias occurred most frequently. The most common reported microorganisms in adult ICUs were non-fermentative Gram-negative bacilli (NFGNB) (33.0%), Enterobacteriaceae (26.5%), Candida spp. (18.2%), Staphylococcus aureus (8.9%), coagulase-negative staphylococci (CoNS) (4.9%) and enterococci (4.5%). In comparison, RCW patients had a higher proportion of NIs caused by S. aureus [odds ratio (OR)=1.9], enterococci (OR=2.2) and Enterobacteriaceae (OR=2.2), but a lower proportion of CoNS (OR=0.3), NFGNB (OR=0.5) and Candida spp. (OR=0.2). RCW patients had higher incidence rates of methicillin-resistant S. aureus (OR=4.91) and extended-spectrum ß-lactamase-producing Enterobacteriaceae (OR=4.06) than ICU patients. Further study is needed to delineate the mechanisms responsible for the differences in resistance profile amongst pathogens associated with nosocomial infection in ICUs, RCCs and RCWs.

Rhabdomyolysis following pandemic influenza A (H1N1) infection.

Rhabdomyalysis is uncommon but potentially life-threatening. We present a 17-year-old patient who developed rhabdomyalysis following pandemic influenza A (H1N1/09) infection. With aggressive hydration her renal function remained normal throughout the entire disease course, and she steadily improved clinically. Although pneumonia and acute respiratory distress syndrome are the most common severe complications of H1N1/09 infection, clinicians should be aware that H1N1/09 infection may be complicated by rhabdomyolysis.

In vitro antibacterial activity of roselle calyx and protocatechuic acid.

The in vitro inhibitory effect of roselle calyx and protocatechuic acid, a compound derived from roselle calyx, on the growth of methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii was studied. The data from inhibition zone and minimum inhibitory concentration (MIC) values showed that both roselle calyx extract and protocatechuic acid inhibited effectively the growth of all test bacterial pathogens, the antibacterial activity of protocatechuic acid being significantly greater than roselle calyx (p < 0.05). Furthermore, heat treatment did not affect the antibacterial activity of roselle calyx and protocatechuic acid against all test pathogens. The time-kill data from protocatechuic acid showed this agent provided concentration dependent antibacterial activities in broth and human plasma (p < 0.05); however, protocatechuic acid showed less inhibitory activity in human plasma than in broth (p < 0.05). These agents based on their lower MIC values, heat tolerance and concentration dependent antibacterial activity may be useful in clinical infection prevention or therapy.

Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation.

In vivo effects of histidine and carnosine against diabetic deterioration in diabetic Balb/cA mice were studied. Histidine and carnosine at 0.5, 1 g/l were added into drinking water. After 4 weeks intake of these agents, the content of histidine and carnosine in plasma, heart and liver significantly elevated (P < 0.05). The intake of these agents significantly decreased plasma glucose and fibronectin levels (P < 0.05); however, only 1 g/l histidine and carnosine treatments significantly increased insulin level (P < 0.05) in diabetic mice. Triglyceride level in heart and liver was dose-dependently reduced by histidine or carnosine treatments (P < 0.05); however, only 1 g/l histidine and carnosine treatments significantly reduced cholesterol level in heart and liver (P < 0.05). The administration of histidine or carnosine significantly enhanced catalase activity and decreased lipid oxidation levels in kidney and liver (P < 0.05); however, only 1 g/l histidine and carnosine treatments significantly increased glutathione peroxidase activity (P < 0.05). The increased interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in diabetic mice were significantly suppressed by the intake of histidine or carnosine (P < 0.05). In human low density lipoprotein, histidine or carnosine showed dose-dependently suppressive effect in glucose-induced oxidation and glycation (P < 0.05). These data suggest that histidine and carnosine are potential multiple-protective agents for diabetic complications prevention or therapy.

Fever of unknown origin: a retrospective study of 78 adult patients in Taiwan.

To elucidate the causes of fever of unknown origin (FUO) in Taiwan, we retrospectively analyzed the characteristics of 78 adult patients meeting the classic criteria for fever of unknown origin who were treated at National Taiwan University Hospital from July 1999 through June 2002. Cause of FUO was due to infections in 42.3% of patients, neoplasms in 6.4%, noninfectious inflammatory diseases in 20.5%, and miscellaneous causes in 7.7%, whereas the cause was not established in 23.1% of patients despite every effort. Tuberculosis (14.1%) and acquired immunodeficiency syndrome (7.7%) were the most common causes of infection in patients with FUO, while intraabdominal abscess, infective endocarditis, and tumor were less frequently found. Noninfectious inflammatory diseases were still a very important cause of FUO and were difficult to diagnose. In conclusion, infection remains the most important cause of classic FUO in Taiwan, confirming the findings in previous series. The importance of tuberculosis and AIDS as frequent causes of FUO should be emphasized.