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Background: Obesity is associated with unfavorable outcomes for infectious diseases. Most researches exploring the association between nutritional status and dengue severity have focused on pediatric populations, with only few studies assessing adult patients. Methods: Adult patients with laboratory-confirmed dengue admitted to a tertiary hospital in southern Taiwan between 2014 and 2015 were enrolled retrospectively. Demographics, comorbidities, clinical presentation, laboratory findings, and outcomes were obtained from caserecord forms. Patients were categorized into obese group and nonobese group. The obese group comprised patients with a body mass index of >= 27.5 kg/m(2). Results: A total of 1417 hospitalized patients with dengue were evaluated. The mean age was 57.9 years (range: 18e92 years). The obese and nonobese groups comprised 333 (23.5%) and 1084 (76.5%) patients, respectively. The obese group included more patients with hypertension (85%, p < 0.001), diabetes mellitus (33%, p < 0.001), and congestive heart failure ( 6.3%, p Z 0.049). Multivariate analysis revealed that the obese group had more petechiae (AOR: 1.353, 95% CI: 1.025e1.786, p Z 0.033), more dyspnea (AOR: 1.380, 95% CI: 1.015e1.876, p Z 0.040), and more severe hepatitis (AOR: 2.061, 95% CI: 1.050e4.048, p Z 0.036). The obese group also had higher peak hematocrit values (44.1%, p < 0.001) and lower nadir platelet count (45.3 x 10(3)/mL, p Z 0.049) than the nonobese group. Conclusion: In adult patients with dengue, obese group had more petechiae, dyspnea, severe hepatitis, lower nadir of platelet count, and higher peak hematocrit level. We observed no difference in severe dengue or mortality between obese and nonobese group.

Background/purpose Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan. Methods A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed. Results Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid. Conclusion Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan.

Background It is unclear about the impact of recreational drug use on the adherence, drug–drug interaction and the occurrence of sexual transmitted diseases (STDs) among people living with HIV. Material and methods A retrospective study was conducted between Dec 2016, and July 2018 to assess the clinical impact of recreational drug consumption in people living with HIV with antiretroviral therapy. We collected data of the demographics, recreational drug use, laboratory results and STDs diagnoses. Potential drug–drug interactions were checked with reference databases. The association between recreational drug use and STDs, HIV viral load suppression and drug interactions were evaluated. Results A total of 462 participants were enrolled, included 384 recreational drug users and 78 non-recreational drug users. Younger age (adjusted odds ratio [aOR], 0.94; 95% CI: 0.91–0.98; p = 0.001), longer HIV infection period (aOR, 1.11; 95% CI: 1.03–1.20; p = 0.009) and poor antiretroviral drug adherence (1–2 pills missing per month: aOR, 6.82; 95% CI: 3.50–13.27; p 2 pills missing per month: aOR, 3.50; 95% CI: 1.28–9.61; p = 0.015) were factors associated with recreational drug use. Methamphetamine and nitrites were two most common recreational drugs. Recreational drug use was significantly associated with STDs in one-year follow-up period (aOR, 2.43; 95% CI: 1.11–5.32; p = 0.027) but was not significantly associated with unsuppressed viral load, though a trend was observed (OR, 2.23; 95% CI: 0.92–5.37; p = 0.074). Potential interactions with recreational drugs included 33.1% antiretroviral drugs and 31.3% medications for comorbidities. Conclusion Recreational drug was associated with STDs. A great proportion of the patients consuming recreational drugs had potential interactions with antiretroviral drugs and medications for comorbidities. The association of recreational drug use and unsuppressed viral load warrants further investigation.

Background Dengue is an arboviral disease caused by dengue virus. Symptomatic dengue infection causes a wide range of clinical manifestations, from mild dengue fever (DF) to potentially fatal disease, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). We conducted a literature review to analyze the risks of DHF and current perspectives for DHF prevention and control. Methods According to the PRISMA guidelines, the references were selected from PubMed, Web of Science and Google Scholar database using search strings containing a combination of terms that included dengue hemorrhagic fever, pathogenesis, prevention and control. Quality of references were evaluated by independent reviewers. Results DHF was first reported in the Philippines in 1953 and further transmitted to the countries in the region of South-East Asia and Western Pacific. Plasma leakages is the main pathophysiological hallmark that distinguishes DHF from DF. Severe plasma leakage can result in hypovolemic shock. Various factors are thought to impact disease presentation and severity. Virus virulence, preexisting dengue antibodies, immune dysregulation, lipid change and host genetic susceptibility are factors reported to be correlated with the development of DHF. However, the exact reasons and mechanisms that triggers DHF remains controversial. Currently, no specific drugs and licensed vaccines are available to treat dengue disease in any of its clinical presentations. Conclusion This study concludes that antibody-dependent enhancement, cytokine dysregulation and variation of lipid profiles are correlated with DHF occurrence. Prompt diagnosis, appropriate treatment, active and continuous surveillance of cases and vectors are the essential determinants for dengue prevention and control.

The tightly regulated biosynthesis and catabolism of the glycosaminoglycan hyaluronan, as well as its role in organizing tissues and cell signaling, is crucial for the homeostasis of tissues. Overexpression of hyaluronan plays pivotal roles in inflammation and cancer, and markedly high serum and tissue levels of hyaluronan are noted under such pathological conditions. This review focuses on the complexity of the regulation at transcriptional and posttranslational level of hyaluronan synthetic enzymes, and the outcome of their aberrant expression and accumulation of hyaluronan in clinical conditions, such as systemic B-cell cancers, aggressive breast carcinomas, metabolic diseases and virus infection.

Background/purpose: The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear. Methods: We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18–64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002–2011. Results: Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01–0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33–9.99). Conclusion: The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications. Keywords: Elderly, Scrub typhus, Acute Q fever, Murine typhus, Complications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative viral pathogen of coronavirus disease 2019 (COVID-19), appears to have various clinical presentations and may result in severe respiratory failure. The global SARS-CoV-2-associated viral pneumonia pandemic was first reported in December 2019 in China. Based on known pharmacological mechanisms, many therapeutic drugs have been repurposed to target SARS-CoV-2. Among these drugs, remdesivir appears to be the currently most promising according to several clinical trials and reports of compassionate use. In this mini-review, we summarize the current evidence on the efficacy and challenges of remdesivir for the treatment of coronavirus disease 2019 (COVID-19).

Background/purpose: For high risk of central line-associated bloodstream infections (CLABSIs) in patients of intensive care units (ICUs) and scarcely epidemiology and therapeutic recommendations in Asia, we aimed to evaluate the annual change in epidemiology, antibiogram, and risk factors for 14-day mortality. Methods: A retrospective study of ICUs patients with CLABSIs at a medical center in Taiwan (2010–2016), where central line care bundle implemented since 2014, by reviewing clinical data, pathogens, and the antibiogram. Results: Gram-negative bacteria (59.3%) were main microorganisms of CLABSIs, and 9.0% of all GNB were MDROs. Acinetobacter spp., Enterobacter spp., and Stenotrophomonas maltophilia were the most frequently isolated. In multivariate analysis, malignancy, inadequate empirical antimicrobial therapy, inadequate definite antimicrobial therapy, and infection by fungi or multidrug-resistant organisms (MDROs) were associated with 14-day mortality (all p

This study examined the susceptibility of carbapenem-nonsusceptible Enterobacterales (CNSE) to cefiderocol, cefepime/zidebactam, cefepime/enmetazobactam, omadacycline, eravacycline and other comparative agents. Non-duplicate Enterobacterales isolates from 16 Taiwanese hospitals were evaluated. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibility results were interpreted based on relevant guidelines. In total, 201 CNSE isolates were investigated, including 26 Escherichia coli isolates and 175 Klebsiella pneumoniae isolates. Carbapenemase genes were detected in 15.4% (n=4) of E. coli isolates and 47.4% (n=83) of K. pneumoniae isolates, with the most common being blaKPC (79.3%, 69/87), followed by blaOXA-48-like (13.8%, 12/87). Cefiderocol was the most active agent against CNSE; only 3.8% (n=1) of E. coli isolates and 4.6% (n=8) of K. pneumoniae isolates were not susceptible to cefiderocol. Among the carbapenem-resistant E. coli and K. pneumoniae isolates, 88.5% (n=23) and 93.7% (n=164), respectively, were susceptible to ceftazidime/avibactam. For cefepime/zidebactam, 23 (88.5%) E. coli isolates and 155 (88.6%) K. pneumoniae isolates had MICs ≤2/2 mg/L. For cefepime/enmetazobactam, 22 (84.6%) E. coli isolates and 85 (48.6%) K. pneumoniae isolates had MICs ≤2/8 mg/L. The higher MICs of K. pneumoniae against cefepime/enmetazobactam were due to only one (1.5%) of the 67 blaKPC-carrying isolates being susceptible. MICs of omadacycline were significantly higher than those of eravacycline and tigecycline. In summary, cefiderocol, ceftazidime/avibactam and cefepime/zidebactam were more effective against carbapenem-nonsusceptible E. coli and K. pneumoniae than other drugs, highlighting their potential as valuable therapeutics.

This study was conducted to investigate the epidemiology and antimicrobial susceptibility patterns of Gram-negative bacilli (GNB) isolated from intra-abdominal infections (IAIs) in the Asia-Pacific region (APR) from 2010-2013. A total of 17 350 isolates were collected from 54 centres in 13 countries in the APR. The three most commonly isolated GNB were Escherichia coli (46.1%), Klebsiella pneumoniae (19.3%) and Pseudomonas aeruginosa (9.8%). Overall, the rates of extended-spectrum β-lactamase (ESBL)-producing E. coli and K. pneumoniae were 38.2% and 24.3%, respectively, and they were highest in China (66.6% and 38.7%, respectively), Thailand (49.8% and 36.5%, respectively) and Vietnam (47.9% and 30.4%, respectively). During 2010-2013, the rates of ESBL-producing E. coli and K. pneumoniae isolates causing community-associated (CA) IAIs (collected48 h after admission) were 26.0% and 13.5%, respectively, and those causing hospital-associated (HA) IAIs were 48.0% and 30.6%, respectively. Amikacin, ertapenem and imipenem were the most effective agents against ESBL-producing isolates. Piperacillin/tazobactam displayed good in vitro activity (91.4%) against CA ESBL-producing E. coli. For other commonly isolated Enterobacteriaceae, fluoroquinolones, cefepime and carbapenems exhibited better in vitro activities than third-generation cephalosporins. Amikacin possessed high in vitro activity against all GNB isolates (80%) causing IAIs, except for Acinetobacter calcoaceticus-baumannii (ACB) complex (30.9% for HA-IAI isolates). All of the antimicrobial agents tested exhibited45% in vitro activity against ACB complex. Antimicrobial resistance is a persistent threat in the APR and continuous monitoring of evolutionary trends in the susceptibility patterns of GNB causing IAIs in this region is mandatory.

Background Evaluation and feedback is a core hand hygiene (HH) improvement strategy. The covert observation method avoids observation bias inherent to the overt method. The aim of the study was to observe HH compliance by a novel covert method in a real-world setting. Methods We conducted a 2-year, nationwide, prospective, observational study in teaching hospitals across Taiwan. Medical students and students who may have contact with patients in their careers were recruited as participants. A novel, shorthand notation method for covert observation was used. Observation results were reported through a study website. Results There were a total of 25,379 HH opportunities covertly observed by 93 observers. Overall HH compliance was 32.0%. Health care workers had the highest HH compliance for indication 4 (42.6%), and the lowest for indication 5 (21.7%). Overall handrubbing percentage was high, reaching 83.6%. The HH compliance increased significantly with an increase in the number of indications within 1 HH opportunity ( P Conclusions The overall HH compliance by the covert observation method was low. An innovative shorthand notation method facilitated covert observation, and website reporting was demonstrated to be feasible for large-scale observation.

A main pathological feature of severe dengue virus infection is endothelial hyperpermeability. We demonstrate that elevated serum hyaluronan levels (≥70 ng/ml)during early infection is an independent predictor for occurrence of warning signs, and thus severe dengue fever. High circulating levels of the viral protein NS1, indicative of disease severity, correlate with high concentration of serum hyaluronan. NS1 exposure decreased the expression of CD44 in differentiating endothelial cells impairing the integrity of vessel-like structures, and promoted the synthesis of hyaluronan in dermal fibroblasts and endothelial cells in synergy with dengue-induced pro-inflammatory mediators. Deposited hyaluronan-rich matrices around cells recruited CD44-expressing macrophages, thus perpetuating inflammation. Perturbed hyaluronan-CD44 interactions enhanced endothelial permeability through modulation of VEcadherin and cytoskeleton re-organization, and exacerbated the NS1 induced disruption of endothelial integrity. Thus, pharmacological targeting of hyaluronan biosynthesis and/or its CD44-mediated signaling may limit the life-threatening vascular leakiness during severe dengue virus infection. Funding Statement: This work was supported in part by grants from the Swedish Cancer Society (2015- 0778), the Swedish research Council (2015-02757), the Ludwig Institute for Cancer Research, Uppsala University, the Ministry of Science and Technology, Taiwan (106- 2314-B-037-088- and 106-2915-I-037-501-), Kaohsiung Medical University Hospital (KMUH103-3T05) and Academy of Finland. Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: The human study protocol was approved by the Institutional Review Board (IRB) of Kaohsiung Medical University Hospital (IRB Number: KMUH-IRB-20110451). Informed consent was obtained from all subjects.

BackgroundInfection is the most common predisposing factor for diabetic ketoacidosis (DKA); however, studies are rare that have investigated the clinical outcomes of septic patients with infection-precipitated DKA.MethodsA retrospective cohort study was conducted at a tertiary hospital from 2004 to 2013. Patients with DKA in whom the presence of a predisposing infection was confirmed were enrolled. Characteristics at initial presentation, primary infection sources, and causative microorganisms were compared between the nonacute kidney injury (non-AKI) group and acute kidney injury (AKI) group at each stage. Risk factors for the development of failure-stage AKI and its outcomes were also analyzed.ResultsOne hundred and sixty DKA episodes were assessed. The most common infection sites were the urinary and respiratory tracts. The leading causative microorganism was Escherichia coli, followed by Klebsiella pneumoniae. A complicated/severe infection state [odds ratio (OR), 15.27; p

The continuing increase in multidrug-resistant organisms (MDROs) worldwide has created new challenges in treating complicated intra-abdominal infections (cIAIs). A number of novel antimicrobial agents have been developed against resistant pathogens. To target extended-spectrum β-lactamase (ESBL)-producing pathogens, novel β-lactam antibiotics, such as ceftolozane/tazobactam, ceftazidime/avibactam, aztreonam/avibactam, imipenem/relebactam and S-649266, are antimicrobial alternatives for cIAIs. Two new drugs, eravacycline and plazomicin, have activity against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, carbapenem-resistant Acinetobacter baumannii and ESBL-producers. New lipoglycopeptides and oxazolidinones provide feasible options against resistant Gram-positive pathogens. These novel antimicrobials may play a role in improving the clinical outcomes of cIAIs caused by MDROs.

The effects of various antimicrobial stewardship programs (ASPs) on both antibiotic consumption and resistance among different hospitals within the same insurance system have rarely been investigated.This 6-year retrospective study included three medical centers with similar facilities and infection control measures in Taiwan. These hospitals used different types of ASPs: one had a hospital-wide preauthorization requirement by infectious diseases physicians for all broad-spectrum antibiotics, covering all intensive care units; the second used the same program, but excluded all intensive care units; and the third used postprescription review only. The nonsusceptibility of unduplicated isolates of gram-negative bacilli causing health care-associated infections and consumption of broad-spectrum antibiotics were analyzed.Overall, the usage of broad-spectrum antibiotics of all classes escalated significantly over time in all three hospitals, but consumption was lowest under the hospital-wide preauthorization program. Under this ASP, despite a 2-fold increase in the total broad-spectrum antibiotic consumption during study period, some declining trends of resistance were found, including ciprofloxacin-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, and carbapenem-resistant P. aeruginosa. By contrast, the other two hospitals with preauthorization program excluding all intensive care units and postprescription review had similar high broad-spectrum antibiotic consumption, comparable growing trends of resistant strains in general, and the correlations of antibiotic consumption and resistance were basically positive. Carbapenem-resistant A. baumannii increased significantly over time in all three hospitals.This interhospital comparison suggested that hospital-wide preauthorization program is the most effective to reduce key gram-negative bacilli resistance, with the exception of carbapenem-resistant A. baumannii.

BackgroundThe Mycobacterium abscessus complex is a common cause of pulmonary nontuberculous mycobacteria infections in Taiwan. We examined the risk factors associated with treatment outcome in Taiwanese adults with pulmonary disease caused by the M. abscessus complex.MethodsWe retrospectively reviewed the records of all patients from a southern Taiwan medical center from 2006 to 2012 who had respiratory specimens identified as M. abscessus complex and met the American Thoracic Society criteria for pulmonary disease.ResultsOf the 106 included patients, females (58.5%) and nonsmokers (79.2%) predominated. The mean age of patients was 64.8 years. Sixty-three patients (59.4%) had pre-existing lung disease. Previous mycobacterial pulmonary disease (34.9%) was the most common underlying disorder. Chest radiography indicated that bronchiectasis was common (47.2%) and that cavitations were less common (14.2%). Fifty-six patients received antibiotic treatment. Clinicians were more likely to prescribe antibiotics if the initial sputum acid-fast staining was positive (p 1 year. Previous mycobacterial pulmonary disease (p = 0.011) and cavitary lesion (p = 0.034) are risk factors for persistence of M. abscessus complex.ConclusionWith antimicrobial therapy, previous mycobacterial disease, and cavitary lesion are associated with microbiologic failure in Taiwanese adults with M. abscessus complex pulmonary disease.

This study was intended to delineate the role of carbapenems and piperacillin/tazobactam in treating bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Proteus mirabilis. We performed a multicenter and retrospective study of the patients with ESBL-producing P. mirabilis bacteremia. The outcomes of the patients treated by piperacillin/tazobactam or a carbapenem for at least 48 hours and the MICs of the prescribed drugs for these isolates were analyzed. Forty-seven patients with available clinical data were included. The overall 30-day mortality rate was 29.8%. All available isolates (n = 44) were susceptible to ertapenem, meropenem, and doripenem, and 95.6% were susceptible to piperacillin/tazobactam; however, only 11.4% of the isolates were susceptible to imipenem. Among the 3 patients infected with isolates exhibiting non-susceptibility to imipenem (MIC ≥2 mg/L) who were treated with imipenem, none died within 28 days. The 30-day (14.3% versus 23.1%, P = 0.65) or in-hospital (19.1% versus 30.8%, P = 0.68) mortality rate of 21 patients treated by a carbapenem was lower than that of 13 treated by piperacillin/tazobactam. However, among those treated by piperacillin/tazobactam, the mortality rate of those infected by the isolates with lower piperacillin/tazobactam MICs (≤0.5/4 mg/L) was lower than that of the isolates with MICs of ≥1/4 mg/L (0%, 0/7 versus 60%, 3/5; P = 0.045). ESBL-producing P. mirabilis bacteremia is associated with significant mortality, and carbapenem therapy could be regarded as the drugs of choice. The role of piperacillin/tazobactam, especially for the infections due to the isolates with an MIC ≤0.5/4 mg/L, warrants more clinical studies.

This study was intended to investigate the trend in vancomycin susceptibility and correlation with molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) causing invasive infections. A total of 670 MRSA isolates were collected from patients with invasive infections as part of bacterial collection in the Tigecycline in vitro Surveillance in Taiwan (TIST) from 2006 to 2010. MICs of the isolates to vancomycin were determined using the agar dilution method. Characteristics of staphylococcal cassette chromosome mec (SCCmec), mec-associated hypervariable region (dru), and accessory gene regulator (agr) of the isolates were identified by polymerase chain reaction methods. MRSA isolates with SCCmec types I, II, and III were molecularly defined as hospital-associated MRSA (HA-MRSA), and those with SCCmec types IV, V, and VT were assigned as community-associated MRSA (CA-MRSA). All but 1 MRSA isolates exhibited vancomycin MICs ≤1 mg/L. A declining trend in vancomycin MICs among MRSA isolates was noted, which was associated with the decline in proportion of HA-MRSA. The percentage of CA-MRSA increased from 25.6% in 2006 to 46.0% in 2010. An increase in the geometric mean of vancomycin MICs was found in MRSA with particular molecular types such as SCCmec types II and III, agr groups I and II, and dru10-14. A significant correlation among particular molecular types was found, including SCCmecII-agr group II-dru4, SCCmecIII-agr group I-dru11-14, SCCmecIV-agr group II-dru9, and SCCmecVT-agr group I-dru9 and dru11. There was no vancomycin creep among MRSA isolates, and the declining trend of vancomycin MIC against MRSA was attributed to the increasing prevalence of CA-MRSA over time.

Summary Objective Suppressors of cytokine signalling (SOCS) proteins regulate cytokine responses and control immune balance. The objective of our study was to determine whether the expression of SOCS1 and its potential regulatory microRNAs (miRNAs) in leukocytes is correlated to the development of dengue haemorrhagic fever (DHF). Methods We performed a case–control study to investigate the SOCS1 and miRNA expression in leukocytes for patients with DF and DHF in a DENV-2 outbreak that occurred in Taiwan between 2002 and 2003. We performed reverse transcription polymerase chain reaction to evaluate the expression of SOCS1 and its regulatory miRNAs in mononuclear leukocytes obtained from patients with or without DHF. The reciprocal relationship between SOCS1 and miR-150 expression was validated in DENV-2-infected peripheral mononuclear cells (PBMCs). Results SOCS1 expression and lower IFN-γ level were significantly reduced in DHF patients, but not in patients with DF. Elevated SOCS1 and reduced miR-150 levels were detected 24 h after DENV-2 infection in PBMCs. Transfection of a miR-150 mimic into CD14 + cells infected with DENV-2 suppressed the induction of SOCS1 expression in a dose-dependent manner. Conclusion We demonstrate for the first time that augmented miR-150 expression with depressed SOCS1 expression in CD14 + cells are associated with the pathogenesis of DHF.

Background/Purpose Stenotrophomonas maltophilia has been recognized as an important nosocomial pathogen, but few reports have discussed S. maltophilia infection in the community settings. This study aimed to reveal characteristics of patients with community-onset S. maltophilia bloodstream infection (SMBSI), to specify the subgroup of healthcare-associated (HCA) infection in the community-onset group and to compare them with hospital-acquired (HA) SMBSI patients. Materials and methods Medical charts of adult patients with SMBSI presenting to a medical center in southern Taiwan from May 2008 to October 2011 were reviewed and analyzed retrospectively. Results Among 153 patients, we observed a high percentage (38.6%) of SMBSI to be community onset. Among community-onset SMBSI, 45.8% were community-acquired (CA) and 54.2% were HCA. The crude mortality rates were 11.1%, 18.8%, and 60.6% in the CA, HCA, and HA groups, respectively. Structural/mechanical abnormalities were observed in 32.7% of all cases, and 60% of those were related to malignancy. Independent risk factors for mortality in community-onset SMBSI were liver cirrhosis, liver metastasis, and a high Pitt bacteremia score, whereas structural/mechanical abnormalities and a high Pitt bacteremia score related to increased mortality in HA SMBSI. Conclusion Community-onset S. maltophilia infection deserves attention. Patients with community-onset SMBSI have reduced disease severity and lower mortality rate when compared to HA SMBSI. Underlying structural/mechanical abnormalities, especially those caused by malignancies, are common in SMBSI cases and should be investigated when bacteremia occurs.

Group A Streptococcal (GAS) necrotizing fasciitis is a critical emergency. Patients with necrotizing fasciitis principally present to emergency departments (EDs), but most studies are focused on hospitalized patients.An ED patient-based retrospective study was conducted to investigate the clinical characteristics, associated factors, and outcomes of GAS necrotizing fasciitis in the ED.Patients visiting the ED from January 2005 through December 2011 with the diagnosis of GAS necrotizing fasciitis were enrolled. All patients with the diagnosis of noninvasive skin and soft-tissue infections caused by GAS were included as the control group.During the study period, 75 patients with GAS necrotizing fasciitis were identified. Males accounted for 84% of patients. The most prevalent underlying disease was diabetes mellitus (45.3%). Bullae were recognized in 37.3% of patients. One third of cases were complicated by bacteremia. Polymicrobial infections were found in 30.7% of patients. Overall mortality rate for GAS necrotizing fasciitis was 16%. Patients aged60 years with diabetes mellitus, liver cirrhosis, and gout were considerably more likely to have GAS necrotizing fasciitis than noninvasive infections. Patients presenting with bacteremia, shock, duration of symptoms/signs5 days, low white blood cell count, low platelet count, and prolonged prothrombin time were associated with increased mortality. Surgery is a significantly negative factor for mortality of patients with GAS necrotizing fasciitis (odds ratio = 0.16; 95% confidence interval 0.002-0.16; p 0.001).A better understanding of the associated factors and initiation of adequate treatments will allow for improved survival after GAS necrotizing fasciitis.

Background/Purpose(s) In 2008, the Dengue NS1 Ag STRIP (Bio-Rad Laboratories, Marnes-la-Coquette, France) was introduced to routine dengue diagnostics in Taiwan, in addition to real-time reverse-transcription polymerase chain reaction (PCR), virus isolation, and capture immunoglobulin (Ig)M/IgG enzyme-linked immunosorbent assay (ELISA). This study aimed to evaluate the benefit of this assay and factors influencing the results of these diagnostic tests. Methods Retrospectively, the authors enrolled laboratory-confirmed adult dengue patients from July 2008 to January 2012 in a tertiary hospital. The sensitivities of each test alone and in combination were analyzed by the duration of illness (early stage: day 0-day 3 and late stage: day 4-day 8). The factors influencing sensitivity of the Dengue NS1 Ag STRIP were examined. Results There were 392 patients enrolled. The overall sensitivity of the Dengue NS1 Ag STRIP was 68.37% and PCR was 71.94%. With the assistance of the Dengue NS1 Ag STRIP, a diagnosis was made in 10.97% of patients without the need for second convalescent samples, and 4.34% more cases were detected. Independent factors for reduced Dengue NS1 Ag STRIP sensitivity were dengue virus (DENV) IgG seropositivity and a sample taken after the fifth day of illness. At the early stage, the PCR and the Dengue NS1 Ag STRIP combination had the highest sensitivity rate than other combinations. At the late stage, a combination of the Dengue NS1 Ag STRIP and capture IgM/IgG ELISA had better sensitivity rates. PCR and capture IgM/IgG ELISA in combination had sensitivity above 90% through the course of illness. Conclusion Dengue NS1 Ag STRIP is a useful tool for early dengue diagnosis. Its use can increase the diagnostic sensitivity and decrease the need of convalescent samples. Seeking treatment late (days postonset > 4) and DENV IgG seropositivity independently decrease the sensitivity of the Dengue NS1 Ag STRIP.

Background This study was undertaken to investigate alterations of group II phospholipase A 2 (PLA 2 ) gene expression and its underlying mechanism in rat heart during different phases of sepsis. Materials and methods Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into three groups, control, early sepsis, and late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 h, respectively, after CLP. PLA 2 enzyme activity, group II PLA 2 protein level, messenger RNA (mRNA) abundance, transcription rate, and half-life were measured. Results PLA 2 activity was decreased by 29% during early sepsis but it was increased by 49% during late sepsis. Group II PLA 2 protein level was decreased by 27% during early sepsis but it was increased by 35.3% during late sepsis. Group II PLA 2 mRNA was decreased by 21% during early sepsis but it was increased by 141% during late sepsis. The transcription rate of group II PLA 2 mRNA was reduced by 25% during early sepsis but it was elevated by 67% during late sepsis. The half-life of group II PLA 2 mRNA remained unaltered during early and late phases of sepsis. Conclusions These results demonstrate that PLA 2 activity, group II PLA 2 protein level, the mRNA abundance, and transcription rate were concurrently underexpressed during early sepsis, while they were overexpressed during late sepsis, with no change in the degradation of gene transcript. These data indicate that the biphasic changes in group II PLA 2 gene expression are regulated transcriptionally during sepsis.

Background Hetero-resistant vancomycin intermediate Staphylococcus aureus (hVISA) emerges worldwide in recent decade. The purpose of this study was to investigate the glycopeptide usage trend, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) with reduced vancomycin susceptibility, the susceptible rates to newer antimicrobials, molecular epidemiology, clinical characteristics, as well as patient outcome among S. aureus bacteremia cases in a Taiwanese medical center. Methods From March to December 2009, among 118 S. aureus blood isolates in a Taiwanese medical center, 62 MRSA isolates were screened for hVISA by Etest macromethod and further confirmed with modified population analysis profiling method. Molecular typing of hVISA isolates was performed. Results Five (4.2%) isolates were hVISA. Compared with non-hVISA MRSA, hVISA isolates had higher resistant rates to ciprofloxacin, gentamicin, trimethoprim/sulfamethoxazole, and tetracycline. Among the MRSA infected, patients infected with hVISA had a higher in-hospital mortality rate than non-hVISA group (60% vs. 17.5%, p = 0.025). All hVISA isolates were nosocomial and had different pulsed field gel electrophoresis pulsotype. Four hVISA isolates carried type III staphylococcal cassette chromosome mec (SCCmec) and the remaining isolate carried SCC mec type II. Three of the 5 hVISA isolates belonged to sequence type 239, which is the most common type in Taiwan. Glycopeptide usage increased in the study hospital; however, these hVISA-infected patients did not receive glycopeptide treatment in the recent 6 months. Conclusion Our results suggested hVISA might have disseminated in the hospital before we observed this highest hVISA rate in Taiwan and increasing glycopeptide usage might serve as selection pressure. Measures to prevent the transmission of MRSA with reduced vancomycin susceptibility and to treat such infection were urgently needed.

Summary We investigated the trends in antimicrobial resistance among species of Gram-negative bacilli isolated from patients with hepatobiliary tract infections in Taiwan during the period 2006–2010 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). During the study period, 1032 isolates of Gram-negative bacilli that had been collected from patients with hepatobiliary infections were tested for susceptibility to 12 antimicrobial agents in accordance with the Clinical and Laboratory Standards Institute guidelines. Enterobacteriaceae accounted for the majority ( n = 874, 84.7%) of isolates and Escherichia coli was the most common pathogen ( n = 323, 31.3%). There were significantly more E. coli ( P = 0.001) and Proteus mirabilis ( P = 0.031) isolates collected from patients who had been hospitalized for less than 48 h and significantly more Serratia marcescens ( P = 0.035) and Pseudomonas aeruginosa ( P = 0.008) isolates collected from patients who had been hospitalized for 48 h or longer. The prevalence of extended–spectrum β–lactamase (ESBL)-producing pathogens was low. The decline in susceptibility rates with time was remarkable for ceftazidime ( P = 0.036), ciprofloxacin ( P = 0.029), and levofloxacin ( P = 0.018). The most effective antibiotics, i.e., those that were active against more than 90% of Enterobacteriaceae, were amikacin, cefepime, imipenem, ertapenem, and piperacillin–tazobactam. Susceptibility of P. aeruginosa to anti-pseudomonal agents was greater than 80%. In this study, we found an overall increase in resistance to antimicrobial agents among Gram-negative bacilli isolated from patients with hepatobiliary tract infections in Taiwan. Surveillance of antimicrobial susceptibility and updates of treatment guidelines are recommended to help achieve optimal therapy for patients with hepatobiliary infections.

In 2009, the Study for Monitoring Antimicrobial Resistance Trends (SMART) was expanded to include surveillance of Gram-negative pathogens causing urinary tract infections (UTIs) in the Asia-Pacific region. A total of 1762 isolates were collected from 38 centers in 11 countries from patients with UTIs in 2009 and 2010. In vitro susceptibilities were determined by the broth microdilution method and susceptibility profiles were determined using minimum inhibitory concentration (MIC) interpretive criteria, as recommended by the Clinical and Laboratory Standards Institute (CLSI) in 2010 (M100-S20), in 2011 (M100-S21), and in 2012 (M100-S22). Enterobacteriaceae comprised 86.0% of the isolates, of which Escherichia coli (56.5%) and Klebsiella pneumoniae (13.8%) were the two most common species. Amikacin was the most effective antibiotic (91.7%), followed by ertapenem (86.9%), imipenem (86.6%), and piperacillin-tazobactam (84.9%). Rates of susceptibility were 50.3% for cefoxitin and ranged from 50.3% to 74.2% for the third- and fourth-generation cephalosporins. For ciprofloxacin and levofloxacin, the susceptibility rates were 51.4% and 54.4%, respectively. Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae comprised 28.2% of all isolates. We also found a high rate of resistance to carbapenems among Acinetobacter baumannii and Pseudomonas aeruginosa causing UTI. Interestingly, according to 2012 CLSI breakpoints, approximately 33.4% of ESBL producers were still susceptible to ceftazidime. However, this in vitro efficacy of ceftazidime needs to be validated in vivo by clinical data. The lowered CLSI interpretive breakpoints for piperacillin-tazobactam, carbapenems, and some cephalosporins in 2011-2012 for Enterobacteriaceae resulted in an approximate 5% drop in susceptibility rates for each drug, with the exception of imipenem for which the susceptibility rate dropped from 99.4% according to 2010 criteria to 91.2% according to 2011 criteria. With the updated CLSI criteria, the antimicrobial resistance threat from UTI pathogens in the Asia Pacific area was revealed to be more prominent.

This paper reports the first successful preparation of biotechnological grade agarose from Gelidium amansii found in Taiwan. The scale-efficiency preparation was achieved by shortening EDTA treatment time through dispersing G. amansii agar in water in the presence of heat and EDTA, removing agaropectin impurity with a heat-compatible and strong-anion exchange resin, and precipitating agarose with a cost-effective isopropanol method. The yield of agarose from prepared G. amansii agar was 11.3%. The acquired agarose has a gel strength of 853 g cm −2 , a sulfate content of 0.14%, a pyruvate content of 1.03%, a degree of electroendosmosis of 0.16 and very limited binding affinity to DNA. The excellent properties of agarose from G. amansii of Taiwan confirm its potential diverse biotechnological applications. This innovative agarose preparation method with the significantly improved scale-efficiency can be modified for large-scale preparation of agarose for use in biotechnological industry and biochemical research.

We investigated the impacts of introducing an expedited acid-fast bacilli (AFB) smear laboratory procedure and an automatic, real-time laboratory notification system by short message with mobile phones on delays in prompt isolation of patients with pulmonary tuberculosis (TB).We analyzed the data for all patients with active pulmonary tuberculosis at a hospital in Kaohsiung, Taiwan, a 1,600-bed medical center, during baseline (January 2004 to February 2005) and intervention (July 2005 to August 2006) phases.A total of 96 and 127 patients with AFB-positive TB was reported during the baseline and intervention phases, respectively. There were significant decreases in health care system delays (ie, laboratory delays: reception of sputum to reporting, P.001; response delays: reporting to patient isolation, P = .045; and interval from admission to patient isolation, P.001) during the intervention phase. Significantly fewer nurses were exposed to each patient with active pulmonary TB during the intervention phase (P = .039).Implementation of expedited AFB smear laboratory procedures and an automatic, real-time laboratory mobile notification system significantly decreased delays in the diagnosis and isolation of patients with active TB.

Summary Objectives The Study for Monitoring Antimicrobial Resistance Trends (SMART) was intended to reveal the evolving profiles of antimicrobial resistance among Gram-negative pathogens causing intra-abdominal infections (IAIs) from Asia-Pacific region in 2009. Methods A total of 3577 aerobic and facultative Gram-negative bacilli associated with IAIs were collected from 32 centers in 12 countries. The in vitro susceptibilities of these isolates to 12 antimicrobial agents were determined using the broth microdilution method. Susceptibility results for selected species of Enterobacteriaceae were also compared using different MIC interpretive criteria recommended by the Clinical and Laboratory Standards Institute in 2009 (M100-S19), in January 2010 (M100-S20), in June 2010 (M100-S20-U) and the European Committee on Antimicrobial Susceptibility Testing in 2010 (EUCAST-2010). Results Enterobacteriaceae comprised 89.5% of the isolates of which Escherichia coli was the most common species (56.7%). Enterobacteriaceae showed poor susceptibility to ampicillin-sulbactam in China (25.3%) and India (19%), and to fluoroquinolones in India (23.4%) and China (37.7%). The rates of extended-spectrum β-lactamase (ESBL)-producing E. coli (36.8%) and Klebsiella pneumoniae (26.3%) remained high. The resistance of ESBL-producing K. pneumoniae to carbapenems also increased, especially to ertapenem (9.9%). Using M100-S20 criteria, 19% of ESBL-producing E. coli and 9% of ESBL-producing K. pneumoniae were susceptible to ceftazidime; 5% and 10% were susceptible to cefepime, respectively. Using M100-S20-U guidelines, the susceptibility rates of ESBL-producing K. pneumoniae (88%) and Enterobacter cloacae (69%) to ertapenem were substantially decreased from those determined using M100-S20. Conclusions These up-to-date epidemiology and antimicrobial resistance surveillance data are crucial to select appropriate treatment of IAIs.

Background/Purpose Surgical site infection (SSI) after cardiac surgery leads to morbidity and mortality. Identifying SSI risk factors, which vary between populations, is important in preventing infection. Methods A retrospective chart review of adult cases receiving cardiac surgery in a Taiwan medical center in 2004 and 2005. Results Of the 260 cases included in the study, 169 (65.0%) received a coronary artery bypass graft, 65 (25.0%) cardiac valvular surgery and 26 (10.0%) aortic or septal defect operations. The SSI rate was 13.5%. Univariate analysis showed that chronic obstructive pulmonary disease (COPD) ( p = 0.008), congestive heart failure New York Heart Association class IV ( p = 0.048), longer preoperative hospital stay, preoperative nosocomial infection, higher volume of blood loss and larger packed red blood cell transfusions during the operation were significantly related to SSI. Logistic regression analysis further identified COPD, pre-operative nosocomial infection and emergency surgery as being independently associated with SSI (odds ratios of 4.96, 5.88 and 9.77, respectively). Obesity and diabetes mellitus were not associated with SSI. Conclusion COPD is an independent underlying illness associated with SSI after cardiac surgery. Minimizing preoperative hospitalization and nosocomial infection, and awareness of cases presenting with relevant risk factors, are useful in reducing SSI.

Background/Purpose The early diagnosis and appropriate management of spinal tuberculosis (TB) is challenging for clinicians. This study aimed to characterize the clinical features and factors affecting treatment outcomes. Methods A retrospective study of patients with spinal TB over a 7-year period at a medical center in southern Taiwan was conducted. Clinical features, underlying diseases, laboratory results, imaging findings, therapy, treatment duration and outcomes were analyzed. Results Forty-eight patients (24 men and 24 women) were diagnosed with spinal TB. Their mean age was 64.3 years. The most common presenting symptoms were backache, neurological deficits, and fever. The most common vertebral area involved was lumbar spine (41.7%). The mean number of vertebra involved was 2.46. Surgery was carried out on 30 patients (62.5%). Patients who had a longer duration of symptoms prior to diagnosis were more likely to have surgery ( p = 0.03), and patients who received surgery had a more favorable outcome ( p = 0.063). The mean treatment course was 11.4 ± 3.7 months. A long course treatment did not contribute to favorable outcomes. Twenty-six patients had a favorable outcome and 11 had an unfavorable outcome. Factors associated with an unfavorable outcome included older age, limb weakness, incontinence, spinal kyphotic deformity, and spinal cord compression. Conclusion For elderly patients with chronic back pain in Taiwan, the differential diagnosis of spinal TB should be considered. Image studies and computed tomography-guided aspiration are helpful for early detection. Combined surgical intervention tended to have a more favorable outcome and longer treatment periods had no additional benefit.

Therapeutic angiogenesis is critical to wound healing and ischemic diseases such as myocardial infarction and stroke. For development of therapeutic agents, a search for new angiogenic agents is the key. Ferulic acid, a phytochemical found in many fruits and vegetables, exhibits a broad range of therapeutic effects on human diseases, including diabetes and cancer. This study investigated the augmenting effect of ferulic acid on angiogenesis through functional modulation of endothelial cells. Through endothelial cell migration and tube formation assays, ferulic acid (10(-6)-10(-4) M) was found to induce significant angiogenesis in human umbilical vein endothelial cells (HUVECs) in vitro without cytotoxicity. With chorioallantoic membrane assay, ferulic acid (10(-6)-10(-5) M) was also found to promote neovascularization in vivo. Using Western blot analysis and quantitative real-time polymerase chain reaction, we found that ferulic acid increased vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) expression in HUVECs. Furthermore, the amounts of hypoxic-induced factor (HIF) 1 alpha mRNA and protein, the major regulator of VEGF and PDGF, also showed up-regulation by ferulic acid. Electrophoretic migration shift assay showed that the binding activity of HIF-1 alpha was also enhanced with ferulic acid treatment of HUVECs. Moreover, inhibitors of extracellular-signal-regulated kinase 1/2 and phosphoinositide-3 kinase (PI3K) abolished the binding activity of HIF-1 alpha and the subsequent activation of VEGF and PDGF production by ferulic acid. Thus, both mitogen-activated protein kinase and PI3K pathways were involved in the angiogenic effects of ferulic acid. Taken together, ferulic acid serves as an angiogenic agent to augment angiogenesis both in vitro and in vivo. This effect might be observed through the modulation of VEGF, PDGF and HIF-1 alpha.

The extracts of Sapindus mukorossi seeds using methanol (MeOH), ethyl acetate (EA) or hexane as solvents were evaluated for their tyrosinase inhibition, free radical scavenging, antimicrobial and anticancer properties. The anti-tyrosinase and antioxidant potentials were determined by in vitro mushroom tyrosinase assay and the radical scavenging method. Both of these results showed minor inhibition abilities at a dosage of 100.0 μg/mL. Antimicrobial activities of S. mukorossi extracts to anti-extensive drug resistant Acinetobacter baumanii (XDRAB) and Pseudomonas aeruginosa (XDRPA) demonstrated good inhibition at 100 μg/mL. The antiproliferative effects of S. mukorossi extracts in human skin, lung, liver, prostate, cervical, bone, bladder, and breast cancer cell lines were also evaluated. Interestingly, S. mukorossi extracts showed strong specific inhibition activities on the proliferation of human melanoma and lung cell lines. The results obtained from biological assays showed that S. mukorossi extracts possessed multiple bioactivities, including anti-tyrosinase, antioxidant, antimicroorganism and anticancer proliferation properties. To our knowledge, this was the first report presenting these bioactivities. The data exhibited the high potential of applying S. mukorossi extracts in medical cosmetology, food supplementation, antibiotics and chemotherapy.

Background/Purpose Sphingomonas paucimobilis is a glucose-nonfermenting Gram-negative bacillus that is widely distributed in both natural environment and hospitals. Various infections in humans have been reported, but most have been limited to sporadic case reports. The aim of this study was to describe the clinical characteristics and manifestations of S. paucimobilis bacteremia. We also reviewed the literature on S. paucimobilis bacteremia. Methods Cases of S. paucimobilis bacteremia were identified retrospectively at a university-affiliated hospital in Taiwan. In addition, relevant case reports were identified through PubMed and reviewed. Results From April 2004 to April 2008, 42 cases of S. paucimobilis bacteremia were identified in this study. Among them, 16 cases were identified from E-Da hospital, Kaohsiung, Taiwan and 26 cases from the literature review. The median age of patients was 48.5 years and 57.1% were male. The most common comorbidities included malignancy (57.1%), immunosuppressant use (40.5%), and diabetic mellitus (11.9%). Hospital-acquired bacteremia accounted for 69.0% of infections. Primary bacteremia and catheter-related bloodstream infection were found in 35.7% and 33.3% respectively. The most effective antibiotics were fluoroquinolones, carbapenems, and β-lactam/β-lactamase inhibitor combinations. All 42 patients survived the S. paucimobilis bacteremic episodes, but three patients experienced septic shock. Conclusion S. paucimobilis can cause infections in healthy as well as immunocompromised individuals. Although it is an organism of low clinical virulence, infection caused by S. paucimobilis can lead to septic shock. Further clinical research is required to characterize this infection.

In this study, 260 non-replicate imipenem-resistant Gram-negative bacteria isolated between January 2002 and December 2006 were subjected to a screening test for detection of metallo-beta-lactamase (MBL) using the Etest containing imipenem and ethylene diamine tetra-acetic acid (EDTA). Among the 260 strains, 123 (47.3%) appeared to produce MBL. Of these 123 strains, 113 (91.9%) were found by polymerase chain reaction (PCR) to carry MBL genes of types blaVIM-2, blaVIM-3, blaVIM-11 (blaVIM-11a), blaIMP-8 and novel blaIMP-24. One strain of Serratia marcescens harboured two MBL genes (blaVIM-11 and blaIMP-8) simultaneously. Of the 123 strains, 116 strains (94.3%) carrying the intI1 gene and 21 strains carrying integron-associated blaVIM-3, blaVIM-11 and blaIMP-8 genes were identified among Acinetobacter baumannii, Pseudomonas aeruginosa, Acinetobacter haemolyticus and S. marcescens. Using pulsed-field gel electrophoresis (PFGE) and Southern hybridisation with the blaVIM gene probe for I-CeuI-digested genomic DNA, P. aeruginosa 9527 strain harboured two class 1 integron-associated MBL genes in the chromosome, including blaVIM-3-orf2-aacA4 and novel bla(VIM-3)-orf2-aacA4-aadB-aacA4. This is the first description of the blaVIM-11 gene spreading among P. aeruginosa and A. baumannii strains in southern Taiwan. This finding suggests that clinical spread of this blaVIM-11 gene is a matter of great concern for carbapenem resistance in southern Taiwan.

Skin manifestations due to intra-abdominal infection are uncommon but could be a warning sign of severe infection. We report a 58-year-old uremic female who had acute cholecystitis and pneumatosis intestinalis. She developed periumbilical hemorrhagic bullae and finally had a fatal outcome with medical therapy. Severe intra-abdominal infection such as pneumatosis intestinalis should be suspected when periumbilical bullae increase in size.

The genetic relationships among dengue virus serotype 2 (DEN-2) isolates from the Taiwan 2002 epidemic were studied by sequence analysis of the envelope (E) and nonstructural protein 1 (NS1) genes. A 0–0.4% divergence among 10 isolates revealed an epidemic strain in the outbreak. Phylogenetic study demonstrated that the 2002 Taiwan isolates were of the Cosmopolitan genotype, which is different from the Asian 1 and Asian 2 genotypes of Taiwan DEN-2 isolates from 1981 to 1998 and the American/Asian genotype of 2005 Taiwan isolates. Although grouping results from both E and NS1 gene sequence analyses were the same, the usage of the NS1 gene as a sequence analysis target has not been validated for the lower bootstrap support values of branches in the phylogenetic tree. Our result showing the same genotype changes in Taiwan and Philippines isolates suggests strain transfer of DEN-2 to nearby countries resulting in the same trend of genotype change.

Annually increasing rates of carbapenem-resistant Acinetobacter spp. were observed in a Taiwan hospital since its establishment in November 1998 to March 2005. Increasing consumption of carbapenems was also noticed. Carbapenem-resistant Acinetobacter spp. from 33 patients carried a class 1 integron. Twenty-eight isolates were Acinetobacter baumannii harbouring both ISAba1 and an OXA-51-like gene. Twenty-four of the 28 A. baumannii isolates had ISAba1 upstream of the OXA-51-like gene. Four A. baumannii isolates harboured the OXA-24-like gene and one isolate had the VIM-11 gene. Regarding the five non-baumannii Acinetobacter spp., three Acinetobacter genomic species 3 isolates and one Acinetobacter radioresistens isolate had both IMP-1 and OXA-58-like genes. One A. radioresistens isolate had an OXA-23-like gene. One major clone of A. baumannii (25/28; 89.3%) was identified by ribotyping. Three ribotypes were identified as being brought into the hospital by patient transfer from other hospitals. In conclusion, an insidious clonal dissemination with various resistance mechanisms contributed to the spread of carbapenem-resistant Acinetobacter spp. in a hospital setting, with increasing usage of carbapenems as the possible selection pressure. Notification of carbapenem-resistant Acinetobacter spp. infection when patients are transferred between hospitals is important to control the spread of carbapenem resistance.

Cat scratch disease (CSD), caused by Bartonella henselae, is a zoonosis and characterized by self-limited lymphadenopathy. It is transmitted commonly by scratch or bite from cats or kitten. We report an unusual case of CSD caused by a domestic dog scratch that we believe is the first report in Taiwan. A 23-year-old healthy woman developed cervical lymphadenopathy, mild fever, headache, and malaise 3 days after dog scratch. Her symptoms improved after azithromycin treatment. Serology proved B. henselae infection. The owners of a domestic dog might be at risk of “cat” scratch disease. [J Formos Med Assoc 2007;106 (2 Suppl):S65-S68]

Ets proteins play a vital role in the regulation of mammalian immunity, and family members Ets-1 and Ets-2 regulate a variety of genes that participate in the propagation of an inflammatory response. Heme oxygenase (HO)-1, although acutely induced by inflammatory stimuli, has cytoprotective properties and prevents an exaggerated inflammatory response. Ets-1 and Ets-2 both induce HO-1 promoter activity; however, Ets-2 was a more potent transactivator of HO-1 in macrophages. A potent inflammatory mediator, bacterial lipopolysaccharide (LPS), induced Ets-2 at the mRNA and protein level, and this induction preceded the up-regulation of HO-1. To further delineate the role of Ets-2 in regulating HO-1 transcription, we performed HO-1 promoter analysis studies in macrophages. Deletion mutants down to –137/+74 maintained an activity analogous to that of the largest construct, –4045/+74. Further deletion constructs (starting with –117/+74) showed a significant reduction in promoter activity when co-transfected with Ets-2 or exposed to LPS. Promoter sequence analysis revealed two putative Ets binding sites (EBSs) in this region, and mutation of these sites showed that EBS –93, more than EBS –125, was critical for full HO-1 promoter activity. Additional studies showed that EBS –93 binds Ets-2 and that mutation of the DNA binding domain of Ets-2 entirely prevented transactivation of HO-1. Finally, overexpression of a dominant negative form of Ets-2 blunted HO-1 promoter induction by LPS, and kinase inhibitors (PI3K more than JNK) that reduced Ets-2 expression markedly decreased endogenous HO-1 expression. Our data provide evidence that Ets-2 contributes to the up-regulation of HO-1 by the potent inflammatory stimulus LPS in macrophages.