Search

Abstract Background Neurological disorders are still prevalent in HIV-infected people. We aimed to determine the prevalence of neurological disorders and identify their risk factors in HIV-infected persons in Taiwan. Methods We identified 30,101 HIV-infected people between 2002 and 2016 from the National Health Insurance Research Database in Taiwan, and analyzed the incidence of neurological disorders. We applied a retrospective, nested case–control study design. The individuals with (case group) and without (control group) a neurological disorder were then matched by age, sex and time. Factors associated with neurological disorders were analyzed using a conditional logistic regression model, and a nomogram was generated to estimate the risk of developing a neurological disorder. Results The incidence of neurological disorders was 13.67 per 1000 person-years. The incidence remained stable during the observation period despite the use of early treatment and more tolerable modern anti-retroviral therapy. The conditional logistic regression model identified nine clinical factors and comorbidities that were associated with neurological disorders, namely age, substance use, traumatic brain injury, psychiatric illness, HIV-associated opportunistic infections, frequency of emergency department visits, cART adherence, urbanization, and monthly income. These factors were used to establish the nomogram. Conclusion Neurological disorders are still prevalent in HIV-infected people in Taiwan. To efficiently identify those at risk, we established a nomogram with nine risk factors. This nomogram could prompt clinicians to initiate further evaluations and management of neurological disorders in this population.

The incidence of COVID-19-associated candidiasis (CAC) is increasing, resulting in a grave outcome among hospitalized patients with COVID-19. The most alarming condition is the increasing incidence of multi-drug resistant Candida auris infections among patients with COVID-19 worldwide. The therapeutic strategy towards CAC caused by common Candida species, such as Candida albicans, Candida tropicalis, and Candida glabrata, is similar to the pre-pandemic era. For non-critically ill patients or those with a low risk of azole resistance, fluconazole remains the drug of choice for candidemia. For critically ill patients, those with a history of recent azole exposure or with a high risk of fluconazole resistance, echinocandins are recommended as the first-line therapy. Several novel therapeutic agents alone or in combination with traditional antifungal agents for candidiasis are potential options in the future. However, for multidrug-resistant C. auris infection, only echinocandins are effective. Infection prevention and control policies, including strict isolation of the patients carrying C. auris and regular screening of non-affected patients, are suggested to prevent the spread of C. auris among patients with COVID-19. Whole-genome sequencing may be used to understand the epidemiology of healthcare-associated candidiasis and to better control and prevent these infections.

COVID-19-associated mold infection (CAMI) is defined as development of mold infections in COVID-19 patients. Co-pathogenesis of viral and fungal infections include the disruption of tissue barrier following SARS CoV-2 infection with the damage in the alveolar space, respiratory epithelium and endothelium injury and overwhelming inflammation and immune dysregulation during severe COVID-19. Other predisposing risk factors permissive to fungal infections during COVID-19 include the administration of immune modulators such as corticosteroids and IL-6 antagonist. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) is increasingly reported during the COVID-19 pandemic. CAPA usually developed within the first month of COVID infection, and CAM frequently arose 10–15 days post diagnosis of COVID-19. Diagnosis is challenging and often indistinguishable during the cytokine storm in COVID-19, and several diagnostic criteria have been proposed. Development of CAPA and CAM is associated with a high mortality despiteappropriate anti-mold therapy. Both isavuconazole and amphotericin B can be used for treatment of CAPA and CAM; voriconazole is the primary agent for CAPA and posaconazole is an alternative for CAM. Aggressive surgery is recommended for CAM to improve patient survival. A high index of suspicion and timely and appropriate treatment is crucial to improve patient outcome.

Background: The geographic distribution of the major clone of sequence type 131 (ST131) in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) infections is not known. We analyzed the clinical features, resistance mechanisms, and geographic distribution of ESBL-producing E. coli clones in 120 children. Methods: We studied the 120 ESBL-producing E. coli strains from children younger than 18 years. A VITEK 2 automated system was used to determine bacterial identification and ESBL production. Sequence type was determined by multi-locus sequence typing (MLST). The genetic relationship of the ESBL-producing strains was studied using pulsed-field gel electrophoresis (PFGE). Phylogenetic group and blaCTX-M group was performed using polymerase chain reaction (PCR). Multiplex PCR for detecting the common group 9 variant, CTX-M-14, and group 1 variant, CTX-M-15, was also performed. The addresses of the 120 children were collected, and plotted on the Taiwan map. Results: The groups in the center of Kaohsiung City lived mainly in urban areas with a population density of over 10,000 people per square kilometer, and the majority of the Kaohsiung groups on the outskirts of the city center lived in suburban areas with a population density of under 6000 people per square kilometer. There was no statistically significant difference between the city center and outskirt groups in terms of clinical presentation, laboratory, and imaging data. However, more ST131 clones, major pulsotype groups, and phylogenetic group B2 strains were found in the center of Kaohsiung than on the outskirts. Conclusion: ESBL-producing E. coli clones may be more challenging to treat clinically. Most infections were community-acquired, and there appeared to be major pulsotype clones, mainly in urban areas. This reinforces the necessity of environmental surveillance and sanitary procedures for ESBL-producing E. coli.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

he first imported case of monkeypox in Taiwan was diagnosed in an Asian man with HIV-1 infection and asymptomatic COVID-19, returning from Germany. Atypical presentations included asynchronous skin lesions, anogenital lesions and prominent inguinal lymphadenopathy. Whole genomic sequence alignment indicate that the Taiwan strain clustered together with human monkeypox virus West African clade B.1, currently circulating in Europe. Prompt diagnosis and infection control measures are crucial to mitigate the spread of monkeypox.

Abstracts: Coronavirus disease 2019 (COVID-19) emerged as a pandemic that spread rapidly around the world, causing nearly 500 billion infections and more than 6 million deaths to date. During the first wave of the pandemic, empirical antibiotics was prescribed in over 70% of hospitalized COVID-19 patients. However, research now shows a low incidence rate of bacterial coinfection in hospitalized COVID-19 patients, between 2.5% and 5.1%. The rate of secondary infections was 3.7% in overall, but can be as high as 41.9% in the intensive care units. Over-prescription of antibiotics to treat COVID-19 patients fueled the ongoing antimicrobial resistance globally. Diagnosis of bacterial coinfection is challenging due to indistinguishable clinical presentations with overlapping lower respiratory tract symptoms such as fever, cough and dyspnea. Other diagnostic methods include conventional culture, diagnostic syndromic testing, serology test and biomarkers. COVID-19 patients with bacterial coinfection or secondary infection have a higher in-hospital mortality and longer length of stay, timely and appropriate antibiotic use aided by accurate diagnosis is crucial to improve patient outcome and prevent antimicrobial resistance.

Antimicrobial drug resistance is one of the major threats to global health. It has made common infections increasingly difficult or impossible to treat, and leads to higher medical costs, prolonged hospital stays and increased mortality. Infection rates due to multidrug-resistant organisms (MDRO) are increasing globally. Active agents against MDRO are limited despite an increased in the availability of novel antibiotics in recent years. This guideline aims to assist clinicians in the management of infections due to MDRO. The 2019 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, comprising of infectious disease specialists from 14 medical centers in Taiwan, reviewed current evidences and drafted recommendations for the treatment of infections due to MDRO. A nationwide expert panel reviewed the recommendations during a consensus meeting in Aug 2020, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes recommendations for selecting antimicrobial therapy for infections caused by carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and vancomycin-resistant Enterococcus. The guideline takes into consideration the local epidemiology, and includes antimicrobial agents that may not yet be available in Taiwan. It is intended to serve as a clinical guide and not to supersede the clinical judgment of physicians in the management of individual patients.

Background: Pneumocystis pneumonia (PCP) is a common opportunistic infection with high mortality in individuals with decreased immunity. Pulmonary coinfections with PCP are associated with poor prognosis. The study aims to identify radiological predictors for pulmonary coinfections in patients with PCP and risk factors for mortality. Methods: This is a retrospective, five-year study was conducted in a medical center, enrolling patients diagnosed with PCP, who received a chest computed tomography (CT) scan. The radiological findings and medical records of all participants were reviewed carefully by 2 independent doctors. Univariable and multivariable analysis was performed to identify radiological predictors for pulmonary coinfection and clinical risk factors for poor prognosis. Results: A total of 101 participants were included, of which 39 were HIV-infected and 62 were non-HIV-infected. In multivariable analysis, radiologic predictors on chest CT for coinfection with bacteria pneumonia included lack of ground glass opacity (adjusted odds ratio [aOR], 6.33; 95% confidence interval [CI], 2.03–19.77; p = 0.001) and presence of pleural effusion (aOR, 3.74; 95% CI, 1.27–10.99; p = 0.017). Predictors for fungal pneumonia included diffuse consolidation (adjusted OR, 6.27; 95% CI, 1.72–22.86; p = 0.005) and presence of pleural effusion (adjusted OR, 5.26; 95% CI, 1.44–19.17; p = 0.012). A significantly higher in-hospital mortality was associated with older age, recent corticosteroid exposure, cytomegalovirus coinfection, and acute respiratory failure. Conclusion: Early identification of pulmonary coinfections in PCP using radiological features on the CT scans, will enable appropriate treatment which is crucial to improve the prognosis.

Background: The detection and treatment of latent tuberculosis infection (LTBI) is a key step in eliminating tuberculosis (TB), but information on safety and on treatment interruption in elderly LTBI patients remains limited. Methods: This multicenter prospective observational study included individuals with LTBI who underwent preventive therapy. Incidents of systemic adverse reactions (SARs) and treatment interruption rates in an elderly group (≥60 years old) and a young group (

Clostridioides difficile infection (CDI) is a major enteric disease associated with antibiotic use and a leading cause of hospital-acquired infections worldwide. This is the first guideline for treatment of CDI in Taiwan, aiming to optimize medical care for patients with CDI. The target audience of this document includes all healthcare personnel who are involved in the medical care of patients with CDI. The 2018 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group was formed, comprising of infectious disease specialists from 13 medical centers in Taiwan, to review the evidence and draft recommendations using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations during a consensus meeting in March 2019. The recommendation is endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline describes the epidemiology and risk factors of CDI, and provides recommendations for treatment of CDI in both adults and children. Recommendations for treatment of the first episode of CDI, first recurrence, second and subsequent recurrences of CDI, severe CDI, fulminant CDI, and pediatric CDI are provided. Keywords: Clostridium difficile, Diarrhea, CDI, Infectious diarrhea

BackgroundA regimen of once-weekly rifapentine plus isoniazid for 3 months (3HP) is an effective treatment for subjects with latent tuberculosis infection; however, no reliable biomarker exists for predicting systemic adverse reactions (SARs) to 3HP treatment.MethodsThis prospective, multi-center study evaluated the plasma concentrations of soluble triggering receptors expressed on myeloid cells (sTREM)-1 and sTREM-2 in subjects undergoing 3HP treatment and examined the associations between these biomarkers and SARs.ResultsThis study enrolled 80 consecutive subjects receiving 3HP treatment, 25 of whom had SARs and 55 of whom did not. Subjects with SARs presented higher concentrations of sTREM-1 at baseline than those without SARs (240.1 ± 19.1 vs. 176.7 ± 9.4 pg/mL, P = 0.001). The area under the receiver operating characteristic curves revealed that day 1 plasma levels of sTREM-1 (0.708, 95% CI, 0.584–0.833, P = 0.003) and sTREM-2 (0.343, 95% CI, 0.227–0.459, P = 0.025) as well as the sTREM-1/sTREM-2 ratio (0.748, 95% CI, 0.638–0.858, P = 0.001) had modest discriminative power pertaining to the development of SARs. An sTREM-1 level exceeding the cut-off value (>187.4 pg/mL) (hazard ratio [HR], 6.15; 95% CI 1.67–22.70, P = 0.006) and a sTREM-2 below the cut-off value (

Background: In Southeast Asia, Japanese encephalitis (JE) is an important cause of viral encephalitis which may cause severe neurological sequelae. JE affects mostly children; therefore, clinical presentations and prognosis of adult JE patients are seldom addressed. This study aimed to describe the clinical characteristics and prognostic factors for the outcome of adult JE patients. Methods: Medical records of adult JE patients with acute encephalitis syndrome during 2001–2018 from five medical centers in southern Taiwan were reviewed. Clinical characteristics, brain images, and prognostic factors for outcomes were analyzed. Patients were divided into the good outcome (GO) group and poor outcome (PO) group according to their Glasgow Coma Scale (GCS) scores (GCS >8 vs. ≤ 8) at discharge. Results: Sixty-eight patients (men, 61.8%; median age, 50 years) were included. Summer is the epidemic season, and the number of cases peaked in June. The most common symptoms at initial presentation were altered consciousness and fever (both 94.1%), followed by headache (51.4%). The most commonly involved brain regions were thalamus (55.7%) and basal ganglion (37.7%). The median GCS score at nadir was 8, and the median time from onset to nadir was five days. Fifty-two patients were included in the GO group, while 16 were included in the PO group. On multivariate analysis, flaccidity, rigidity, and elevated CSF protein level were identified as independent prognostic factors for PO. Conclusion: Initial clinical presentations of abnormal muscle tone including flaccidity, rigidity and high CSF protein levels are independent prognostic factors for PO in adult JE patients. Keywords: Adult, Japanese encephalitis, Outcome, Prognostic factor

Background: Extraintestinal pathogenic Escherichia coli (ExPEC) strains hold the responsibility for the majority of E. coli infections. Numerous extraintestinal virulence factors (VFs) were possessed by ExPEC which are involved in the pathogenesis of infection. However, the effect of comorbidities or infection syndrome in the association of VFs and mortality remains inconclusive. Method: This study addressed whether specific sequence type (ST) and VFs of extended-spectrum beta-lactamase–producing E. coli (ESBL-EC) are associated with different outcomes in patients with bloodstream infection. 121 adults from southern Taiwan with ESBL-EC bloodstream infections were enrolled during a 6-year period. Demographic data, including infection syndromes, underlying disease and outcomes, were collected. The virulence factors in isolates were analyzed by PCR and multilocus sequence typing analyses were also performed. Result: Positivity for the virulence genes iha, hlyD, sat, iutA, fyuA, malX, ompT, and traT was associated with ST131 positivity (P

Abstract Background The use of fixed combination antiretroviral therapy with a low genetic barrier for the treatment of patients infected with human immunodeficiency virus (HIV) may affect the local HIV transmitted drug resistance (TDR) pattern. The present study aimed to investigate changes in the prevalence of HIV TDR following the implementation of a fixed regimen of HIV treatment in Taiwan in 2012. Methods TDR was measured in antiretroviral treatment-naïve HIV-1-infected individuals who participated in voluntary counseling and testing between 2007 and 2015 in southern Taiwan. Antiretroviral resistance mutations were interpreted using the HIVdb program from the Stanford University HIV Drug Resistance Database. Results Sequences were obtained from 377 consecutive individuals between 2007 and 2015. The overall prevalence rates of TDR HIV among the study population from 2007 to 2011 and 2012–2015 were 10.6 and 7.9%, respectively. Among the detected mutations, K103 N and V179D + K103R were more frequently observed after 2012. Four HIV-infected patients with K103 N variants were detected after 2012, and 4 of the 5 patients with V179D + K103R variants were found after 2012. No significant differences were observed in the TDRs among nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), protease inhibitors, multiple drug resistance, and any drug resistance between period 1 (2007–2011) and period 2 (2012–2015). Conclusions A fixed treatment regimen with zidovudine/lamivudine + efavirenz or nevirapine as first-line therapy for treatment-naïve patients infected with HIV did not significantly increase the TDR during the 4-year follow-up period. Due to the increase in NNRTI resistance associated with mutations after 2012, a longer follow-up period and larger sample size are needed in future studies.

Executive Summary: Pneumonia is a leading cause of death worldwide, ranking third both globally and in Taiwan. This guideline was prepared by the 2017 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, formed under the auspices of the Infectious Diseases Society of Taiwan (IDST). A consensus meeting was held jointly by the IDST, Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM), the Medical Foundation in Memory of Dr. Deh-Lin Cheng, the Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines. The final guideline was endorsed by the IDST and TSPCCM. The major differences between this guideline and the 2007 version include the following: the use of GRADE methodology for the evaluation of available evidence whenever applicable, the specific inclusion of healthcare-associated pneumonia as a category due to the unique medical system in Taiwan and inclusion of recommendations for treatment of pediatric pneumonia. This guideline includes the epidemiology and recommendations of antimicrobial treatment of community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, healthcare-associated pneumonia in adults and pediatric pneumonia. Keywords: Pneumonia, Guidelines, Treatment, Taiwan

Rapidly growing mycobacteria (RGM) has gained increasing clinical importance, and treatment is challenging due to diverse drug resistance. The minimum inhibitory concentrations (MIC) of 13 antimicrobial agents using modified broth microdilution and E-test were determined for 32 clinical isolates of RGM, including Mycobacterium abscessus (22 isolates) and Mycobacterium fortuitum (10 isolates). Our results showed high rates of resistance to available antimicrobial agents. Amikacin remained highly susceptible (87.5%). Clarithromycin was active against the isolates of M. abscessus (95.5%), and M. fortuitum (50%), but 36.4% and 20% had inducible macrolide resistance, respectively. Rates of susceptibility to tigecycline were 68.2–70%, and linezolid 45.5–50%, respectively. The quinolones (ciprofloxacin and moxifloxacin) showed better in vitro activity against M. fortuitum isolates (50% susceptibility) than the M. abscessus isolates (31.8% susceptibility). The susceptibilities to other conventional anti-mycobacterial agents were poor. The MICs of E-test were higher than broth microdilution and may result in reports of false resistance. In conclusion, the implementation of the modified broth microdilution plates into the routine clinical laboratory workflow to provide antimicrobial susceptibility early, allows for the timely selection of appropriate treatment of RGM infections to improve outcome.

Background Mycobacterium abscessus (MAB) has emerged as the predominant pulmonary non-tuberculous mycobacterial pathogen in parts of Asia, including Taiwan. The reasons for the significant increase in MAB infections in the non-cystic fibrosis (CF) populations are poorly understood. The study aimed to elucidate whether this increase is related to the spread of the globally successful clone of MAB. Methods We performed multilocus sequence typing of 371 nonduplicated MAB pulmonary isolates from 371 patients sampled between 2010–2017 at seven hospitals across Taiwan. Results In total, 183 (49.3%) isolates were M. abscessus subsp. abscessus (MAB-a), 187 (50.4%) were M. abscessus subsp. massiliense (MAB-m), and 1 (0.3%) was M. abscessus subsp. bolletii (MAB-b). MAB-a sequence type (ST)1 (23.7%) and ST127 (3.8%), followed by MAB-m ST48 (16.2%), ST117 (15.1%), ST23 (8.6%) were most common overall. Of MAB-a strains, 50 (27.3%) belonged to novel STs and 38 (10.2%) were singleton strains, while of MAB-m strains, only 10 (5.3%) were novel and 8 (2.2%) were singletons. From 2010 to 2017, the frequency of the historically dominant ST1 declined from 28.6% to 22.5%, whereas the recently emerged globally successful clonal cluster 3, ST23 and ST48, increased from 14.3% to 40.0%. Conclusions The dominance of ST1 particularly in the last 2 years of this study appears to be declining, while ST23, reported in outbreaks among CF and post-surgical cohorts across the Americas and Europe, alongside the closely related ST48, is present among non-CF populations in Taiwan. These trends need to be confirmed with further ongoing studies to track the molecular epidemiology of clinical MAB isolates worldwide.

Nontuberculous mycobacterial infections and colonization are becoming more prevalent worldwide. Mycobacterium abscessus complex (MABC) is one of the predominant pathogens capable of a wide spectrum of infections, with 50% of infections involving the lungs. The decision to commence treatment is determined according to the severity of the disease, risk of progressive disease, presence of comorbidities, and goals of treatment. MABC is resistant to standard antituberculous agents and has variable drug susceptibility across different geographical locations, therefore, antibiotic susceptibility testing of all clinically significant isolates is crucial for selecting a treatment strategy. Pulmonary infections due to MABC is difficult to cure using the currently recommended regimens from the American Thoracic Society and British Thoracic Society. Macrolides are the cornerstone of treatment, but the efficacy of macrolide-based chemotherapy may be compromised by resistance. Despite the introduction of new drugs for treatment, treatment outcomes remain unsatisfactory. The combination of surgical resection of limited lung disease regions with a multidrug, macrolide-based therapy offers the optimal chance of achieving clinical cure of the disease. This review focuses on medical treatment of MABC–lung disease and the efficacy of new agents, such as clofazimine, amikacin inhalation therapy, tigecycline and linezolid, for treating MABC–lung disease.

BACKGROUND:Carbapenem-resistant Klebsiella pneumoniae (CRKP) is emerging as a significant pathogen causing healthcare-associated infections. Matrix-assisted laser desorption/ionisation mass spectrometry time-of-flight mass spectrometry (MALDI-TOF MS) is used by clinical microbiology laboratories to address the need for rapid, cost-effective and accurate identification of microorganisms. We evaluated application of machine learning methods for differentiation of drug resistant bacteria from susceptible ones directly using the profile spectra of whole cells MALDI-TOF MS in 46 CRKP and 49 CSKP isolates. METHODS:We developed a two-step strategy for data preprocessing consisting of peak matching and a feature selection step before supervised machine learning analysis. Subsequently, five machine learning algorithms were used for classification. RESULTS:Random forest (RF) outperformed other four algorithms. Using RF algorithm, we correctly identified 93% of the CRKP and 100% of the CSKP isolates with an overall classification accuracy rate of 97% when 80 peaks were selected as input features. CONCLUSIONS:We conclude that CRKPs can be differentiated from CSKPs through RF analysis. We used direct colony method, and only one spectrum for an isolate for analysis, without modification of current protocol. This allows the technique to be easily incorporated into clinical practice in the future.

Background/Purpose: The prevalence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. This study investigated the clinical features and bacteriology of pediatric patients with ESBL-producing E. coli bacteremia and compared their characteristics with those of adult patients. Methods: Clinical and laboratory data from all of the 41 patients aged ≤18 years diagnosed with E. coli bacteremia were collected over 5 years. Patients aged >18 years diagnosed with E. coli bacteremia, matched 1:1 for calendar time, were enrolled as the adult group. All E. coli isolates were tested for their blaCTX-M group and sequence type 131 (ST131). A novel seven-single nucleotide polymorphism-based clonotyping test was applied to detect the septatypes of each isolate. Results: In the adult group, patients with ESBL-producing E. coli bacteremia had more previous hospitalizations and antimicrobial agent use than did those with non-ESBL-producing E. coli bacteremia, but these differences were not found in pediatric group. In the pediatric group, the proportion of isolates producing CTX-M group 9 was higher than that in the adult group (85.7% vs. 42.9%; p

Abstract Background Observation and feedback are core strategies of hand hygiene (HH) improvement. Direct overt observation is currently the gold standard method. Observation bias, also known as the Hawthorne effect, is a major disadvantage of this method. Our aim was to examine the variation of the Hawthorne effect on HH observation in different healthcare groups and settings. Methods A prospective cohort study was performed in a tertiary teaching hospital during a 15-month period. Up to 38 overt observers (82% nurses) and 93 covert observers (81% medical students) participated in HH observation. The HH events observed overtly were matched for occupation, department, observation time, and location with those observed covertly. The data of matched pairs were then analysed to detect possible Hawthorne effects on different variables. Results A total of 31,522 HH opportunities were observed (4581 overtly, 26,941 covertly). There were 3047 matched pairs after 1:1 matching of overt and covert observations. The overall HH compliance was higher with overt observation than with covert observation (78% vs. 55%, p

Abstract Background Whether the non-inferior efficacy and safety results of switching virologically suppressed HIV-1-infected patients from nevirapine immediate-release (NVP-IR) to NVP extended-release (NVP-XR) demonstrated in the TRANxITION study conducted in Europe and North America are also applicable to virologically suppressed HIV-infected Taiwanese patients remains unknown. We evaluated the comparative safety and efficacy of continuing NVP-IR versus switching to NVP-XR in virologically suppressed HIV-infected Taiwanese adults receiving combined antiretroviral therapy (cART) regimens. Methods We conducted a retrospective cohort study at Kaohsiung Veterans General Hospital from April 1, 2013, to March 31, 2015. Eighty-four virologically suppressed HIV-infected adults receiving NVP-IR cART were split into two groups: those continuing with NVP-IR (n = 49) and those being switched to NVP-XR (n = 35). Demographic characteristics, clinical variables, and laboratory findings were compared. Therapeutic drug monitoring of steady-state plasma NVP concentrations and genotype analysis of CYP2B6 516 were also performed in 22 participants. The primary endpoint was continued virological suppression at the end of the study. Secondary endpoints were time to loss of virological response and adverse events. Results During a mean follow-up of 18.4 months, the NVP-XR group demonstrated similar success at maintaining virological response compared with the NVP-IR group (82.9% vs. 85.7%; P = 0.72). Cox regression analysis indicated that there were no significant differences between NVP regimens for time to loss of virological response (hazard ratio: 0.940; P = 0.754). Furthermore, there were no significant differences in adverse events between these two groups. In the 22 participants, there was a non-significantly lower level of steady-state plasma NVP concentrations in the NVP-XR group than in NVP-IR recipients (5145.0 ng/mL vs. 6775.0 ng/mL; P = 0.267). The prevalence of CYP2B6 516 GT was 86.6%, and there was no significant difference in the distribution of CYP2B6 516 between these two groups. Conclusions We found that switching from NVP-IR to NVP-XR appeared to have similar safety and efficacy compared with continuing NVP-IR among virologically suppressed, HIV-infected Taiwanese patients. Our finding of higher Ctrough levels in both groups compared with other studies conducted in Caucasian populations and the high prevalence of CYP2B6 516 GT requires further investigation in a larger Taiwanese cohort.

The 14-3-3 proteins are cerebrospinal fluid (CSF) markers of neuronal damage during infectious meningitis and Creutzfeldt-Jakob disease. Little is known about dynamic changes in the individual isoforms in response to parasitic eosinophilic meningitis. The purposes of this study were to determine the 14-3-3 protein isoform patterns, examine the kinetics and correlate the severity of blood brain barrier (BBB) damage with the expressions of these markers in mice with eosinophilic meningitis. Mice were orally infected with 50 A. cantonensis L3 via an oro-gastric tube and sacrificed every week for 3 consecutive weeks after infection. The Evans blue method and BBB junctional protein expressions were used to measure changes in the BBB. Hematoxylin and eosin staining was used to analyze pathological changes in the mice brains following 1-3 weeks of infection with A. cantonensis. The levels of 14-3-3 protein isoforms in serum/CSF and brain homogenates were analyzed by Western blot, and immunohistochemistry (IHC) was used to explore the different isoform distributions of 14-3-3 proteins and changes in BBB junctional proteins in the mice brain meninges. Dexamethasone was injected intraperitoneally from the seventh day post infection (dpi) until the end of the study (21 dpi) to study the changes in BBB junctional proteins. The amounts of Evans blue, tight junction and 14-3-3 protein isoforms in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. There were significant increases in 14-3-3 protein isoforms β and γ in the CSF in the second and third weeks after infection compared to the controls and first week of infection, which were correlated with the severity of BBB damage in brain histology, and Evans blue extravasation. Using IHC to assess the distribution of 14-3-3 protein isoforms and changes in BBB junctional proteins in the mice brain meninges, the expressions of isoforms β, γ, ε, and θ and junctional proteins occludin and claudin-5 in the brain meninges increased over a 3-week period after infection compared to the controls and 1 week after infection. The administration of dexamethasone decreased the expressions of BBB junctional proteins occludin and claudin-5 in the mice brain meninges. Our findings support that 14-3-3 proteins β and γ can potentially be used as a CSF marker of neuronal damage in parasitic eosinophilic meningitis caused by A. cantonensis.

Background: This study aimed to investigate the frequency of sequence type (ST) 131 strains and outcome of cirrhotic patients with bloodstream infections (BSIs) caused by extended-spectrum beta-lactamase-producing Escherichiacoli (ESBLEC) and non-extended-spectrum beta-lactamase-producing Escherichiacoli (NESBLEC). Methods: The incidence of ST 131 strains, hospital stay, and 30-day re-admission/mortality were compared between 51 ESBLEC and 51 NESBLEC bacteremic patients with cirrhosis. Results: ST 131 strains were found in 35.3% of the ESBLEC group and 0% of the NESBLEC group (p < 0.001). Mean hospital stay was 26.5 days in the ESBLEC group and 17.1 days in the NESBLEC group (p = 0.006). Thirty-day re-admission rates were 11.8% in the ESBLEC group and 5.9% in the NESBLEC group (p = 0.5). ST 131 strains were associated with 30-day re-admission (odds ratio: 4.5, 95% confidence interval: 1.1–18.9). Thirty-day mortality rate was 31.4% in the ESBLEC group and 23.5% in the NESBLEC group (p = 0.4). Conclusion: In patients with cirrhosis, the ESBLEC BSIs group had a higher frequency of ST 131 strains and longer hospital stay than the NESBLEC BSIs group with similar 30-day re-admission/mortality. ST 131 strains were associated with 30-day re-admission.

Rapid identification of mycobacteria is important for timely treatment and the implementation of public health measures. The MGIT system ensures rapid detection of mycobacteria, but identification is usually delayed by days to weeks due to further subculture on solid medium. Matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS) was demonstrated to effectively identify mycobacteria isolates subcultured from solid or liquid media. Reports of identification directly from MGIT broths of both sterile and non-sterile clinical specimens, omitting the subculture step, were limited and not satisfactory before. Our identification method dramatically shortened delay from detection to identification of mycobacteria.We assessed the performance of the Vitek MS IVD version 3.0 for direct identification of NTM and M.tuberculosis from primary MGIT cultures, and assessed two sample preparation methods.Direct identification of NTM from positive MGIT broths, using MALDI-TOF VITEK MS with IVD v.3.0, generated high rates of acceptable results reaching 96.4% (80/83), and up to 100% (83/83) for sample preparations including a 0.1% SDS washing step. The sensitivity of VITEK MS to identify M.tuberculosis from MGIT tubes was 58/72 (80.6%), when using immunochromatography (ICA) test as gold standard. A characteristic colony clumping, wool-like appearance was observed in 48, and all 58 (100%) were correctly identified as M.tuberculosis using MALDI-TOF. The detection rate of M.tuberculosis complex was low (10/24, 41.6%) in the 24 MGIT tubes that was polymicrobial. Our method significantly reduced both the reagent cost and turnaround time.Based on a simplified protocol, we showed that MALDI-TOF MS can be used for rapid identification of NTM directly from primary MGIT cultures within the routine clinical laboratory workflow. However, we recommend an initial ICA test to screen for M.tuberculosis complex, due to a low identification rate of M. tuberculosis in the presence of polymicrobial cultures using MALDI-TOF.

Patients with acute lobar nephronia (ALN) require a longer duration of antimicrobial treatment than those with acute pyelonephritis (APN), and ALN is associated with renal scarring. The aim of this study was to provide an understanding of ALN by comparing the clinical features of pediatric patients with ALN and APN. Methods: We enrolled all of the patients with ALN (confirmed by computed tomography) admitted to our hospital from 1999 to 2012 in the ALN group. In addition, each patient diagnosed with APN who was matched for sex, age, and admission date to each ALN patient was enrolled in the APN group. The medical charts of patients in these two groups were retrospectively reviewed and analyzed for comparison. Results: The fever duration after hospitalization in the ALN group and the APN group were 4.85 ± 2.33 days and 2.30 ± 1.47 days respectively. The microbiological distributions and the majority of susceptibilities were similar in the ALN and APN groups. The majority of clinical manifestations are nonspecific and unreliable for the differentiation of ALN and APN. The patients with ALN were febrile for longer after antimicrobial treatment, had more nausea/vomiting symptoms, higher neutrophil count, bandemia, and C-reactive protein (CRP) levels, and lower platelet count (all p 5 days after antimicrobial treatment.

Abstract Background Angiostrongylus cantonensis, the rat lungworm, is the major cause of eosinophilic meningitis worldwide. Rats serve as the definitive host of the nematode, but humans can be infected incidentally, leading to eosinophilic meningitis. A previous BALB/c animal study has demonstrated increased apoptotic proteins and decreased anti-apoptotic proteins in mice infected with A. cantonensis. Steroids may be an effective treatment option for eosinophilic meningitis caused by A. cantonensis, but the involved mechanism is unclear. This study hypothesized that the beneficial effects of steroids on eosinophilic meningitis are mediated by decreased apoptosis. Methods In a BALB/c animal model, mice were orally infected with 50 A. cantonensis L3 via an oro-gastric tube and were sacrificed every week for 3 consecutive weeks after infection or until the end of the study. Dexamethasone was injected intra-peritoneally from the 7th day post-infection until the end of the 21-day study. Evans blue method was used to measure changes in the blood brain barrier, while western blotting, immuno-histochemistry, and TUNEL assay were used to analyze brain homogenates expression of apoptotic and anti-apoptotic proteins. Results There were increased amounts of Evans blue, apoptotic proteins (caspase-3, -8, and -9 and cytochrome C), and decreased anti-apoptotic proteins (bcl-2) after 2-3 weeks of infection. Dexamethasone administration significantly decreased Evans blue extravasations and apoptotic protein expressions. Conclusions Apoptosis of mice brain homogenates can be repressed by dexamethasone treatment.

BACKGROUND:Dengue fever is an important arboviral disease. The clinical manifestations vary from a mild non-specific febrile syndrome to severe life-threatening illness. The virus can usually be detected in the blood during the early stages of the disease. Dengue virus has also been found in isolated cases in the cerebrospinal fluid, urine, nasopharyngeal sections and saliva. In this report, we describe the isolation of dengue virus from the upper respiratory tract of four confirmed cases of dengue. METHODS:We reviewed all laboratory reports of the isolation of dengue virus from respiratory specimens at the clinical microbiology laboratory of the Kaohsiung Veterans General Hospital during 2007 to 2015. We then examined the medical records of the cases from whom the virus was isolated to determine their demographic characteristics, family contacts, clinical signs and symptoms, course of illness and laboratory findings. RESULTS:Dengue virus was identified in four patients from a nasopharyngeal or throat culture. Two were classified as group A dengue (dengue without warning signs), one as group B (dengue with warning signs) and one as group C (severe dengue). All had respiratory symptoms. Half had family members with similar respiratory symptoms during the period of their illnesses. All of the patients recovered uneventfully. CONCLUSIONS:The isolation of dengue virus from respiratory specimens of patients with cough, rhinorrhea and nasal congestion, although rare, raises the possibility that the virus is capable of transmission by the aerosol route among close contacts. This concept is supported by studies that show that the virus can replicate in cultures of respiratory epithelium and can be transmitted through mucocutaneous exposure to blood from infected patients. However, current evidence is insufficient to prove the hypothesis of transmission through the respiratory route. Further studies will be needed to determine the frequency of respiratory colonization, viable virus titers in respiratory secretions and molecular genetic evidence of transmission among close contacts.

Bile esculin azide with vancomycin (BEAV) medium is a sensitive, but slightly less specific method for vancomycin-resistant enterococci (VRE) screening. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a rapid method for identification of clinical pathogens. This study aimed to assess the performance of a novel combination screening test for VRE, using BEAV broth combined with MALDI-TOF MS.Clinical specimens were collected from patients at risk of VRE carriage, and tested by the novel combination method, using selective BEAV broth culture method followed by MALDI-TOF MS identification (SBEAVM). The reference method used for comparison was the ChromID VRE agar method.A total of 135 specimens were collected from 78 patients, and 63 specimens tested positive for VRE positive using the ChromID VRE method (positive rate 46.7%). The sensitivity, specificity, positive predictive value, and negative predictive value of SBEAVM method after an incubation period of 28 hours were 93.7%, 90.3%, 89.4%, and 94.2%, respectively. The SBEAVM method when compared to the ChromID VRE method had a shorter turnaround time (29 vs. 48-72 hours) and lower laboratory cost ($2.11 vs. $3.23 per test).This study demonstrates that SBEAVM is a rapid, inexpensive, and accurate method for use in VRE screening.

Active efflux is known to play a major role in the resistance of many bacteria to antibiotics. To evaluate the possibility of overcoming resistance by suppressing the efflux, we determined the effect of reserpine, an efflux pump inhibitor. Methods: Intracellular accumulations and the minimal inhibitory concentrations (MICs) of ciprofloxacin in M. tuberculosis H37Rv and 16 clinical isolates were determined, compared, and analyzed. Nine of the clinical isolates were resistant to isoniazid and rifampin (multiple-drug resistant MDR). Five of these were resistant to ciprofloxacin. Results: A reserpine-inhibited efflux system was identified in the H37Rv control and 10:1 (90.9%) of ciprofloxacin-susceptible and 4:1 (80%) of ciprofloxacin-resistant clinical isolates. The MIC of ciprofloxacin decreased in the presence of reserpine in 3/10 (30%) of the ciprofloxacin-susceptible and 2/4 (50%) of the MDR ciprofloxacin-resistant strains that expressed efflux pumps. Two of the efflux-positive, ciprofloxacin-resistant strains in which the MIC of ciprofloxacin was not decreased by reserpine were found to carry a D94A gyrA mutation. In contrast, two strains with the D94G gyrA mutation were susceptible to ciprofloxacin in the presence of reserpine. An efflux-negative strain, highly resistant to multiple antibiotics, was found to have a novel G247S mutation that differs from known mutations in the QRDR region of the gyrA gene. Conclusion: These findings indicate t hat reserpine can increase intracellular concentrations of ciprofloxacin, but is unable to overcome other mechanisms of resistance in clinical isolates.

Mycobacterium avium complex (MAC) is frequently considered to be a contaminant or transient colonizer. To the best of our knowledge, there have been very few reports regarding the clinical significance of MAC isolates in respiratory specimens, and the associated disease spectrum in Taiwan. The purpose of this study was to investigate the clinical significance of MAC isolates in respiratory specimens. Methods: We retrospectively reviewed the medical records of patients in a medical center in Southern Taiwan from whom MAC isolates were recovered from respiratory specimens, and analyzed their clinical features, chest imaging findings, treatment and prognosis. We also performed an antibiotic susceptibility test on our MAC isolates. Results: The 64 isolates used in this study were recovered from April to October 2001 from respiratory specimens in 54 patients admitted to Kaohsiung Veterans General Hospital, Taiwan. According to the 2007 criteria of the American Thoracic Society, a total of 12 patients (22.2%) had clinically significant MAC pulmonary disease. Conclusion: Despite the increased frequency of recovering MAC from respiratory specimens, most cases did not meet the criteria of American Thoracic Society for clinically significant nontuberculous pulmonary disease. The minimum inhibitory concentrations of drugs against these MAC isolates might help to guide treatment, but further studies should be done.

To understand the resistance patterns of rapidly growing mycobacteria (RGM) in Taiwan, antimicrobial resistance of clinical isolates was determined as part of the SMART (Surveillance from Multicenter Antimicrobial Resistance in Taiwan) program. Methods: During the period from January 2002 to December 2003, clinical isolates were collected from eight hospitals located on the west side of Taiwan and one reference laboratory. Broth microdilution minimum inhibitory concentrations of 11 antimicrobial agents were determined for 312 clinical isolates of RGM, including the Mycobacterium fortuitum group (110 isolates), Mycobacterium abscessus group (168 isolates), and Mycobacterium chelonae group (34 isolates). Results: Nearly all of the RGM were susceptible to amikacin and ofloxacin (≥ 90%) and resistant to doxycycline (< 3% susceptible). Tobramycin showed similar in vitro activity against the M. fortuitum and M. chelonae (77%) groups, but was less active against the M. abscessus group (58%). Ciprofloxacin was active mainly against M. fortuitum (95%). Nearly all RGM were resistant to erythromycin and doxycycline. However, around half of the RGM isolates remained susceptible to minocycline (50-54%). Clarithromycin was active against the M. abscessus group (53% susceptible), with a high rate of resistance in the M. chelonae (38% susceptible) and M. fortuitum (15% susceptible) group. Cefoxitin was more active against the M. fortuitum group (65%) than the other two RGM (40-44%), and < 40% of the RGM isolates remained susceptible to imipenem (21-38%). Conclusion: The resistance of RGM in Taiwan is not as high as previously reported (notably for tobramycin, ciprofloxacin and cefoxitin), but reduction in the susceptibility rates of clarithromycin and imipenem for the M. fortuitum and M. abscessus groups demonstrates the importance of in vitro susceptibility testing of clinically important isolates, as susceptibility may differ in different geographical areas, even regionally, and over time.

BACKGROUND:Predicting the risk of tuberculosis (TB) in people living with HIV (PLHIV) using a single test is currently not possible. We aimed to develop and validate a clinical algorithm, using baseline CD4 cell counts, HIV viral load (pVL), and interferon-gamma release assay (IGRA), to identify PLHIV who are at high risk for incident active TB in low-to-moderate TB burden settings where highly active antiretroviral therapy (HAART) is routinely provided. MATERIALS AND METHODS:A prospective, 5-year, cohort study of adult PLHIV was conducted from 2006 to 2012 in two hospitals in Taiwan. HAART was initiated based on contemporary guidelines (CD4 count < = 350/μL). Cox regression was used to identify the predictors of active TB and to construct the algorithm. The validation cohorts included 1455 HIV-infected individuals from previous published studies. Area under the receiver operating characteristic (ROC) curve was calculated. RESULTS:Seventeen of 772 participants developed active TB during a median follow-up period of 5.21 years. Baseline CD4 < 350/μL or pVL ≥ 100,000/mL was a predictor of active TB (adjusted HR 4.87, 95% CI 1.49-15.90, P = 0.009). A positive baseline IGRA predicted TB in patients with baseline CD4 ≥ 350/μL and pVL < 100,000/mL (adjusted HR 6.09, 95% CI 1.52-24.40, P = 0.01). Compared with an IGRA-alone strategy, the algorithm improved the sensitivity from 37.5% to 76.5%, the negative predictive value from 98.5% to 99.2%. Compared with an untargeted strategy, the algorithm spared 468 (60.6%) from unnecessary TB preventive treatment. Area under the ROC curve was 0.692 (95% CI: 0.587-0.798) for the study cohort and 0.792 (95% CI: 0.776-0.808) and 0.766 in the 2 validation cohorts. CONCLUSIONS:A validated algorithm incorporating the baseline CD4 cell count, HIV viral load, and IGRA status can be used to guide targeted TB preventive treatment in PLHIV in low-to-moderate TB burden settings where HAART is routinely provided to all PLHIV. The implementation of this algorithm will avoid unnecessary exposure of low-risk patients to drug toxicity and simultaneously, reduce the burden of universal treatment on the healthcare system.

Pyogenic liver abscess in Taiwan is a well-known disease entity, commonly associated with a single pathogen, Klebsiella pneumoniae. Melioidosis is an endemic disease in Taiwan that can manifest as multiple abscesses in sites including the liver. We report three cases of liver abscesses caused by Burkholderia pseudomallei. The first patient was a 54-year-old diabetic woman, who presented with liver abscess and a left subphrenic abscess resulting from a ruptured splenic abscess, co-infected with K. pneumoniae and B. pseudomallei. The second patient, a 58-year-old diabetic man, developed bacteremic pneumonia over the left lower lung due to B. pseudomallei with acute respiratory distress syndrome, and relapsed 5 months later with bacteremic abscesses of the liver, spleen, prostate and osteomyelitis, due to lack of compliance with prescribed antibiotic therapy. The third patient was a 61-year-old diabetic man with a history of travel to Thailand, who presented with jaundice and fever of unknown origin. Liver and splenic abscesses due to B. pseudomallei were diagnosed. A high clinical alertness to patients' travel history, underlying diseases, and the presence of concomitant splenic abscess is essential to early detection of the great mimicker, melioidosis. The treatment of choice is intravenous ceftazidime for at least 14 days or more. An adequate duration of maintenance oral therapy, with amoxicillin-clavulanate or trimethoprim-sulfamethoxazole for 12-20 weeks, is necessary to prevent relapse. Liver abscess in Taiwan is most commonly due to K. pneumoniae, but clinicians should keep in mind that this may be a presenting feature of melioidosis.