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Background: The prevalence of mild cognitive impairment (MCI) exhibits a positive correlation with age, particularly evident in the old-old female population. Lifestyle factors have been identified as crucial risk determinants for MCI. However, there is a scarcity of research focusing on lifestyle factors among young-old population., Objective: This study aimed to explore the lifestyle factors associated with MCI in young-old male and female., Methods: This study employed a cross-sectional design and utilized demographic and lifestyle data obtained from participants enrolled in the Taiwan Biobank (TWB) between 2008 and 2021, with 32,897 individuals aged 60 to 70 years old. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with a total score ranging from 0 to 30 points. The cut-off of MCI scores was ≤18, ≤21, and ≤25 according to the education level, respectively. Logistic regression analysis was employed to assess the association between lifestyles and cognitive function., Results: 3,878 individuals (11.78%) suffered from MCI. Upon gender stratification, high exercise metabolic equivalents in male (OR = 0.8, 95% CI: 0.70 - 0.92) and moderate exercise in female serve as protective factors for MCI (OR = 0.78, 95% CI: 0.70 - 0.87). Additionally, diversified dietary preferences among female (OR = 0.80, 95% CI: 0.66 - 0.97) also emerge as protective factors for cognitive function., Conclusions: It is worth noting that male is advised to target a higher exercise metabolic equivalent, while female can attain cognitive benefits with moderate exercise and diversified dietary.

Background: A predominate azole-resistant Candida tropicalis clade 4 genotype causing candidemia has been detected in not only Taiwan but also China, Singapore, and Australia. It can also be detected on fruit surfaces. In addition to determining distribution and drug susceptibilities of pathogenic yeasts in environments of intensive care units of 25 hospitals in Taiwan, we would also like to investigate whether the azole-resistant C. tropicalis exists in Taiwan's hospital environment., Methods: The swabs of hospital environments were collected from August to November in 2020 and were cultured for yeasts. The yeasts were identified by rDNA sequence and the antifungal susceptibilities of those isolates were determined by the broth microdilution method., Results: The average yeast-culture rate of hospitals was 9.4% (217/2299). Sinks had the highest yeast-positive culture rate (32.7%), followed by bedside tables (28.9%), floors (26.0%), water-dispenser buttons (23.8%), and TV controller/touch panels (19.0%). Of 262 identified isolates, Candida parapsilosis was the most common species, accounting for 22.1%, followed by Filobasidium uniguttulatum (18.3%), Candida albicans (9.5%), C. tropicalis (8.0%), Candida glabrata (Nakaseomyces glabratus) (6.9%), and 30 other species (35.1%). Of the 21 C. tropicalis isolates from 11 units in 9 hospitals, 15 diploid sequence types (DSTs) were identified. The two DST506 fluconazole-resistant ones belonged to clade 4., Conclusion: We detected not only various pathogenic yeast species but also the predominant clade 4 genotype of azole-resistant C. tropicalis. Our findings highlight and re-emphasize the importance of regular cleaning and disinfection practices., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Campylobacteriosis is a common cause of bacterial gastroenteritis worldwide. This study aimed to investigate the potential risk factors, clinical and laboratory manifestations of children with campylobacteriosis under five years old in Taiwan., Methods: This retrospective case-control study was conducted in ten major hospitals in Taiwan from 2014 to 2017. Laboratory tests and stool specimen were collected and analyzed together with questionnaire survey. Multivariate stepwise logistic regression model was used for identification of risk factors., Results: A total of 64 campylobacteriosis cases were included with a median age of 25 months. We observed a less prolonged vomiting (p = 0.047), more bloody (p < 0.001) and mucoid (p = 0.005) stools, and lower AST levels (p = 0.020) in patients with campylobacteriosis. Lower parental educational attainment (p < 0.001), direct contact with acute gastroenteritis patients (p < 0.001), as well as diarrhea in the mutually cared children (p = 0.007) were linked to campylobacteriosis. Consumption of municipal water (p < 0.001), milk (OR 0.34, 95% CI 0.118-0.979), and soft beverages (OR 0.41, 95% CI 0.192-0.888) were identified as protective factors, while consuming takeout food (p = 0.032) and seafood (p = 0.019) increased risk of campylobacteriosis., Conclusions: Shorter vomiting duration, bloody and mucoid stool, and less elevated AST levels are manifestations suggestive of campylobacteriosis. Risk factors of campylobacteriosis were low parental educational attainment, direct contact with acute gastroenteritis patients, diarrhea in mutually cared children, takeout food and seafood intake. Potential protective factors include municipal water, milk, and soft beverage intake., Competing Interests: Declaration of competing interest None., (© 2023 Chang Gung University. Publishing services provided by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

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., (© 2023. The Author(s).)

Objectives: Monkeypox has recently been detected outside African countries. This study aimed to report and analyze the first case of monkeypox virus infection in Taiwan., Methods: The global epidemiological information was collected from the World Health Organization (WHO) and US Centers for Disease Control and Prevention (CDC). The data from the first confirmed Taiwanese monkeypox case was obtained from Taiwan Centers for Disease Control. Monkeypox diagnosis and prevention strategies were obtained from WHO guidelines on monkeypox. Phylogenetic tree analysis and sequence alignment and comparison were used to identify the phylogeny and single nucleotide polymorphism (SNP) characterization., Results: Epidemiological data indicated that since 2013, monkeypox has caused outbreaks outside African countries through contact with infected animals and international travels. Recently, two confirmed monkeypox cases were reported in Singapore and South Korea. On June 24, 2022, Taiwan CDC reported the first confirmed case of monkeypox virus infection in a 20-year-old man who returned from Germany, from January to June 2022. This is the third confirmed case of an imported monkeypox infection in Asia. Phylogenetic analysis demonstrated that this imported monkeypox virus belonged to the West African clade and is clustered with the 2022 European outbreak monkeypox isolates. Full-length sequence analysis indicates that this virus contains 51 SNPs, and has five variant SNPs compared with the recent outbreak strains., Conclusion: This study suggests that active surveillance, enhancing border control, and the development of vaccines and antiviral drugs are urgently required to prevent and control the burden of monkeypox disease., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: During the COVID-19 pandemic, the need for influenza vaccine significantly increased in the initial weeks of the 2020-2021 influenza vaccination campaign season in Taiwan. To meet this demand, the Taiwanese government therefore purchased additional influenza vaccines via special import, including 350,000 doses of quadrivalent recombinant influenza vaccines (RIV4, Flublok Quadrivalent). Approved in the United States since 2016, there were limited numbers of published studies regarding RIV4 outside America. We utilized the national passive surveillance system consisting adverse event (AE) reports following RIV4 immunization to describe its safety profiles in Taiwan., Methods: We obtained the database from the Taiwan National Adverse Drugs Reactions Reporting System and collected reports from January 2021 to July 2021, which was at least one month after RIV4 immunization. AE reporting rates were calculated based on the total administered doses., Results: Eight AEs were reported among 200,287 administered doses, which led to a reporting rate of 3.99 AEs per 100,000 doses administered. The mean age of the reported individuals were 47.53 years, and women (75%) were the predominant gender. Most adverse events started within the first day after immunization, with one reported as starting 4 days after vaccination. Among the 8 cases, 75% (n = 6) were non-serious and the most common symptoms were erythematous skin rashes with pruritus. Two cases were listed as serious based on the criteria of "other clinically significant medical conditions", but neither was judged to have a causal relationship with RIV4 immunization., Conclusion: The Taiwan national passive surveillance data supported the safety profiles of RIV4 in Taiwan population., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S-YT and T-YY are currently employed by Sanofi and may hold shares and/or stock options in the company. N-CC and C-TH have no relevant conflict of interest to report., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To explore the in vitro antimicrobial susceptibility among clinically important Gram-negative bacteria (GNB) in Taiwan., Methods: From 2016 through 2018, a total of 5458 GNB isolates, including Escherichia coli (n = 1545), Klebsiella pneumoniae (n = 1255), Enterobacter species (n = 259), Pseudomonas aeruginosa (n = 1127), Acinetobacter baumannii complex (n = 368), and Stenotrophomonas maltophilia (n = 179), were collected. The susceptibility results were summarized by the breakpoints of minimum inhibitory concentration (MIC) of CLSI 2020, EUCAST 2020 (for colistin), or published articles (for ceftolozane/tazobactam). The resistance genes among multidrug-resistant (MDR) or extensively drug-resistant (XDR)-GNB were investigated by multiplex PCR., Results: Significantly higher rates of non-susceptibility (NS) to ertapenem and carbapenemase production, predominantly KPC and OXA-48-like beta-lactamase, were observed in Enterobacterales isolates causing respiratory tract infection than those causing complicated urinary tract or intra-abdominal infection (12.7%/3.44% vs. 5.7%/0.76% or 7.7%/0.97%, respectively). Isolates of Enterobacter species showed higher rates of phenotypic extended-spectrum β-lactamase and NS to ertapenem than E. coli or K. pneumoniae isolates. Although moderate activity (54-83%) was observed against most potential AmpC-producing Enterobacterales isolates, ceftolozane/tazobactam exhibited poor in vitro (44.7-47.4%) activity against phenotypic AmpC Enterobacter cloacae isolates. Additionally, 251 (22.3%) P. aeruginosa isolates exhibited the carbapenem-NS phenotype, and their MDR and XDR rate was 63.3% and 33.5%, respectively. Fifteen (75%) of twenty Burkholderia cenocepacia complex isolates were inhibited by ceftolozane/tazobactam at MICs of ≤4 μg/mL., Conclusions: With the increase in antibiotic resistance in Taiwan, it is imperative to periodically monitor the susceptibility profiles of clinically important GNB., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

To monitor trends in the distribution of yeast species and the susceptibilities of these species to commonly prescribed antifungal drugs, we conduct the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) every 4 years. We found that 25 of 294 Candida tropicalis isolates from TSARY 2014 and 31 of 314 C. tropicalis isolates from TSARY 2018 were resistant to fluconazole. We determined the genetic relatedness among fluconazole-resistant C. tropicalis isolates by multilocus sequence typing (MLST). Among 174 C. tropicalis isolates, including all 56 fluconazole-resistant, all 26 susceptible-dose dependent and 92 selected fluconazole-susceptible isolates, 59 diploid sequence types (DSTs) were identified. We found that 22 of the 25 fluconazole-resistant C. tropicalis from TSARY 2014 and 29 of the 31 fluconazole-resistant C. tropicalis from TSARY 2018 were genetically related and belonged to the same cluster (clade 4). A combination of mutation and overexpression of ERG11, encoding the target of azole drugs, was the major mechanism contributing to drug resistance. Approximately two-thirds of reviewed patients infected or colonised by fluconazole-resistant C. tropicalis were azole-naïve. Furthermore, there was no evidence of patient-to-patient transmission. Because the clade 4 fluconazole-resistant C. tropicalis strain persists in Taiwan, it is important to identify the source of azole-resistant C. tropicalis to prevent the spread of this resistant strain., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background/purpose: Acute gastroenteritis (AGE) remains a significant health issue in children. The worldwide evolution of pediatric AGE pathogens had been recorded since the introduction of rotavirus vaccine. Ten years after the rotavirus vaccine was introduced to the private sectors in Taiwan, a nationwide study was conducted to elucidate the epidemiological changes among major AGE pathogens., Methods: From January 2014 to December 2017, children younger than 5 years old, hospitalized with AGE at 10 hospitals across Taiwan were enrolled. Stool specimens were tested for Salmonella spp., Campylobacter spp., Clostridiodes difficile, norovirus, and rotavirus by polymerase chain reaction (PCR). The epidemiological and clinical information was collected., Results: Enteric pathogen were detected in 1983 (42.2%) of 4700 subjects, with Salmonella spp. (12.5%) being the leading cause of AGE, followed by norovirus (11.2%), rotavirus (8.7%), C. difficile (4.2%), Campylobacter spp. (1.0%), and a mixture of at least 2 of 5 above-mentioned pathogens (4.6%). The case distributions varied across different regions. In eastern Taiwan, rotavirus (21/131, 16.0%) remained the most common pathogen detected. The rotavirus vaccine uptake rate is significantly lower in patients with rotavirus AGE. Besides, rotavirus AGE frequently occurred in children with foreign parent(s), Taiwanese indigenous people, and those with the household monthly income < NT$ 60,000., Conclusion: Salmonella spp. and norovirus were two major pathogens of pediatric AGE in Taiwan during 2014-17. Providing low-to middle-income households with free rotavirus vaccine nationwide and an industry-led act to reduce salmonellosis should be considered by the authorities., Competing Interests: Declaration of competing interest The authors declared no conflicts of interest., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Expansion of genotype I (GI) Japanese encephalitis viruses (JEV) has resulted in the replacement of the dominant genotype III (GIII) viruses, raising serious public health concerns for using GIII virus-derived vaccines to effectively control JEV epidemics. Therefore, this study used swine as the model to estimate the effectiveness of GIII live-attenuated vaccine against GI virus infection by comparing the incidence of stillbirth/abortion in gilts from vaccinated and non-vaccinated pig farms during the GI-circulation period. In total, 389 and 213 litters of gilts were recorded from four vaccinated and two non-vaccinated pig farms, respectively. All viruses detected in the aborted fetuses and mosquitoes belonged to the GI genotype during the study period. We thus estimated that the vaccine effectiveness of GIII live-attenuated vaccine against GI viruses in naive gilts based on the overall incidence of stillbirth/abortion and incidence of JEV-confirmed stillbirth/abortion was 65.5% (50.8-75.7%) and 74.7% (34.5-90.2%), respectively. In contrast to previous estimates, the GIII live-attenuated vaccine had an efficacy of 95.6% (68.3-99.4%) to prevent the incidence of stillbirth/abortion during the GIII-circulating period. These results indicate that the vaccine effectiveness of GIII live-attenuated JEV vaccine to prevent stillbirth/abortion caused by GI viruses is lower than that against GIII viruses.

Background: Integrase strand transfer inhibitor (InSTI)-based regimens have become the major first-line treatment for HIV-1-infected patients in Taiwan. Transmitted drug resistance (TDR) and several clinical characteristics are associated with time to virological failure or viral suppression; however, these have not been investigated in Taiwan., Objectives: To determine the impact of several factors on treatment outcomes in HIV-1-infected patients in Taiwan., Methods: The cohort included 164 HIV-1 treatment-naive patients in Taiwan from 2018 to 2020. Blood specimens were collected to determine the genotypic drug resistance using the Stanford University HIV drug resistance database. Cox proportional hazards models were used to identify factors associated with time to virological failure or viral suppression., Results: The prevalence of TDR in Taiwan was 27.4% and an increasing trend was seen from 2018 to 2020. TDR mutations related to NNRTIs were the most prevalent (21%) while TDR to InSTIs remained at a relatively low level (1.3%). A baseline HIV-1 viral load of ≥100 000 copies/mL was associated with a shorter time to virological failure [multivariate hazard ratio (mHR) 7.84; P = 0.018] and longer time to viral suppression (mHR 0.46; P < 0.001). Time to viral suppression was shorter in patients receiving InSTI-based regimens (mHR 2.18; P = 0.006). Different InSTI-based regimens as initial treatment did not affect the treatment outcomes., Conclusions: This study found an increasing trend of HIV-1 TDR prevalence from 2018 to 2020 in Taiwan. Baseline HIV-1 viral load and receiving InSTI-based regimens are important factors associated with time to virological failure or viral suppression., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: MVC-COV1901, a recombinant protein vaccine containing pre-fusion-stabilised spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide, has been shown to be well tolerated with a good safety profile in healthy adults aged 20-49 years in a phase 1 trial, and provided a good cellular and humoral immune responses. We present the interim safety, tolerability, and immunogenicity results of a phase 2 clinical trial of the MVC-COV1901 vaccine in Taiwan., Methods: This is a large-scale, double-blind, randomised, placebo-controlled phase 2 trial done at ten medical centres and one regional hospital in Taiwan. Individuals aged 20 years or older who were generally healthy or had stable pre-existing medical conditions were eligible for enrolment. Exclusion criteria included (but were not limited to) travel overseas within 14 days of screening, intention to travel overseas within 6 months of the screening visit, and the absence of prespecified medical conditions, including immunosuppressive illness, a history of autoimmune disease, malignancy with risk to recur, a bleeding disorder, uncontrolled HIV infection, uncontrolled hepatitis B and C virus infections, SARS-CoV-1 or SARS-CoV-2 infections, an allergy to any vaccine, or a serious medical condition that could interfere with the study. Study participants were randomly assigned (6:1) to receive two doses of either MVC-COV1901 or placebo, administered via intramuscular injection on day 1 and day 29. MVC-COV1901 contained 15 μg of S-2P protein adjuvanted with 750 μg CpG 1018 and 375 μg aluminium hydroxide in a 0·5 mL aqueous solution, and the placebo contained the same volume of saline. Randomisation was done centrally by use of an interactive web response system, stratified by age (≥20 to <65 years and ≥65 years). Participants and investigators were masked to group assignment. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from day 1 (the day of the first dose) to day 57 (28 days after the second dose). Safety was assessed in all participants who received at least one dose. Immunogenicity was assessed by measuring geometric mean titres (GMTs) and seroconversion rates of neutralising antibody and antigen-specific IgG in the per-protocol population. This study is registered with ClinicalTrials.gov, NCT04695652., Findings: Of 4173 individuals screened between Dec 30, 2020, and April 2, 2021, 3854 were enrolled and randomly assigned: 3304 to the MVC-COV1901 group and 550 to the placebo group. A total of 3844 participants (3295 in the MVC-COV1901 group and 549 in the placebo group) were included in the safety analysis set, and 1053 participants (903 and 150) had received both doses and were included in the per-protocol immunogenicity analysis set. From the start of this phase 2 trial to the time of interim analysis, no vaccine-related serious adverse events were recorded. The most common solicited adverse events in all study participants were pain at the injection site (2346 [71·2%] of 3295 in the MVC-COV1901 group and 128 [23·3%] of 549 in the placebo group), and malaise or fatigue (1186 [36·0%] and 163 [29·7%]). Fever was rarely reported (23 [0·7%] and two [0·4%]). At 28 days after the second dose of MVC-COV1901, the wild-type SARS-CoV-2 neutralising antibody GMT was 662·3 (95% CI 628·7-697·8; 408·5 IU/mL), the GMT ratio (geometric mean fold increase in titres at day 57 vs baseline) was 163·2 (155·0-171·9), and the seroconversion rate was 99·8% (95% CI 99·2-100·0)., Interpretation: MVC-COV1901 has a good safety profile and elicits promising immunogenicity responses. These data support MVC-COV1901 to enter phase 3 efficacy trials., Funding: Medigen Vaccine Biologics and Taiwan Centres for Disease Control, Ministry of Health and Welfare., Competing Interests: Declaration of interests CC, CEL, and I-CT are employees of Medigen Vaccine Biologics (Taipei, Taiwan) and they report receiving grants from Taiwan Centres for Disease Control, Ministry of Health and Welfare, during the conduct of the study. CC also has a patent pending relating to the MVC-COV1901 vaccine against SARS-CoV-2 (US17/351,363). All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Norovirus is a common acute gastroenteritis (AGE) pathogen across all age groups worldwide, which is difficult to differentiate from other pathogens. This study aimed to understand the clinical characteristics and risk factors of norovirus gastroenteritis among children in Taiwan., Methods: A prospective AGE surveillance study was conducted in children aged ≤5 years who were hospitalized in 10 major hospitals in Taiwan between 2014 and 2017. The non-AGE control group included healthy children who were matched based on age, gender, season, and geographic area., Results: Overall, 674 norovirus gastroenteritis patients were enrolled. Fever (p < 0.001), mucoid stool (p < 0.001), and bloody stool (p < 0.001) occurred less frequently among norovirus gastroenteritis patients. Norovirus gastroenteritis patients yielded lower CRP values on admission (21.78 ± 36.81 vs. 46.26 ± 58.12 mg/L, p < 0.001) than non-norovirus controls. Norovirus gastroenteritis patients were associated with higher direct contact rates with AGE patients within 1 week (30.5% vs. 0.97%, p < 0.001), lower hand wash rates before meals (21.6% vs. 15.4%, p = 0.001), lower human milk (15.8% vs. 19.8%, p = 0.045) and guava consumption rates (17.8% vs. 24.3%, p = 0.002) than non-AGE participants., Conclusions: Body temperature, stool characteristics, and CRP value can help distinguish the norovirus from other pathogens. The major risk factor of norovirus AGE is contact with AGE patient. Higher frequency of hand wash, human milk, and guava intake may be protective against norovirus gastroenteritis., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to disclose., (Copyright © 2020. Published by Elsevier B.V.)

Multicenter surveillance of antimicrobial susceptibility was performed for 235 vancomycin-resistant Enterococcus faecium (VREfm) isolates from 18 Taiwanese hospitals. The minimum inhibitory concentrations (MICs) of eravacycline, omadacycline, lipoglycopeptides, and other comparator antibiotics were determined using the broth microdilution method. Nearly all isolates of VREfm were not susceptible to teicoplanin, dalbavancin, and telavancin, with susceptibility rates of 0.5%, 1.7% and 0.5%, respectively. Tigecycline and eravacycline were active against 93.2% and 89.7% of the VREfm isolates, respectively. Moreover, the susceptibility rates of quinupristin/dalfopristin, tedizolid, and linezolid were 59.1%, 84.2%, and 77.4%, respectively. Additionally, 94% of the VREfm isolates were classified as susceptible to daptomycin, and the MICs of omadacycline required to inhibit VREfm growth by 50% and 90% were 0.12 and 0.5 mg/L, respectively. Susceptibility rates of VREfm isolates to synthetic tetracyclines and daptomycin were slightly lower and to oxazolidinone-class antibiotics were much lower in Taiwan than those in other parts of the world. Continuous monitoring of VREfm resistance to novel antibiotics, including synthetic tetracyclines, oxazolidinone-class antibiotics, and daptomycin, is needed in Taiwan., (Copyright © 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

The emergence of carbapenem-resistant Enterobacterales (CRE) has become a major public health concern. Moreover, its colonization among residents of long-term care facilities (LTCFs) is associated with subsequent infections and mortality. To further explore the various aspects concerning CRE in LTCFs, we conducted a literature review on CRE colonization and/or infections in long-term care facilities. The prevalence and incidence of CRE acquisition among residents of LTCFs, especially in California, central Italy, Spain, Japan, and Taiwan, were determined. There was a significant predominance of CRE in LTCFs, especially in high-acuity LTCFs with mechanical ventilation, and thus may serve as outbreak centers. The prevalence rate of CRE in LTCFs was significantly higher than that in acute care settings and the community, which indicated that LTCFs are a vital reservoir for CRE. The detailed species and genomic analyses of CRE among LTCFs reported that Klebsiella pneumoniae is the primary species in the LTCFs in the United States, Spain, and Taiwan. KPC-2-containing K. pneumoniae strains with sequence type 258 is the most common sequence type of KPC-producing K. pneumoniae in the LTCFs in the United States. IMP-11- and IMP-6-producing CRE were commonly reported among LTCFs in Japan. OXA-48 was the predominant carbapenemase among LTCFs in Spain. Multiple risk factors associated with the increased risk for CRE acquisition in LTCFs were found, such as comorbidities, immunosuppressive status, dependent functional status, usage of gastrointestinal devices or indwelling catheters, mechanical ventilation, prior antibiotic exposures, and previous culture reports. A high CRE acquisition rate and prolonged CRE carriage duration after colonization were found among residents in LTCFs. Moreover, the patients from LTCFs who were colonized or infected with CRE had poor clinical outcomes, with a mortality rate of up to 75% in infected patients. Infection prevention and control measures to reduce CRE in LTCFs is important, and could possibly be controlled via active surveillance, contact precautions, cohort staffing, daily chlorhexidine bathing, healthcare-worker education, and hand-hygiene adherence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Jean, Lee, Lu, Ko, Liu and Hsueh.)

Objectives Dental problems occur widely in patients with chronic kidney disease (CKD) and may increase comorbidities. Root canal therapy (RCT) is a common procedure for advanced decayed caries with pulp inflammation and root canals. However, end-stage renal disease (ESRD) patients are considered to have a higher risk of potentially life-threatening infections after treatment and might fail to receive satisfactory dental care such as RCT. We investigated whether appropriate intervention for dental problems had a potential impact among dialysis patients. Design Men and women who began maintenance dialysis (hemodialysis or peritoneal dialysis) between January 1, 2000, and December 31, 2015, in Taiwan (total 12,454 patients) were enrolled in this study. Participants were followed up from the first reported dialysis date to the date of death or end of dialysis by December 31, 2015. Setting Data collection was conducted in Taiwan. Results A total of 2633 and 9821 patients were classified into the RCT and non-RCT groups, respectively. From the data of Taiwan's National Health Insurance, a total of 5,092,734 teeth received RCT from 2000 to 2015. Then, a total of 12,454 patients were followed within the 16 years, and 4030 patients passed away. The results showed that members of the non-RCT group (34.93%) had a higher mortality rate than those of the RCT group (22.79%; p = 0.001). The multivariate-adjusted hazard ratio for the risk of death was 0.69 (RCT vs. non-RCT; p = 0.001). Conclusions This study suggested that patients who had received RCT had a relatively lower risk of death among dialysis patients. Infectious diseases had a significant role in mortality among dialysis patients with non-RCT. Appropriate interventions for dental problems may increase survival among dialysis patients. Abbreviations: CKD = chronic kidney disease, ESRD = end-stage renal disease, RCT = root canal therapy.

Background: Community onset K. pneumoniae bacteremia (KPB) is a major problem in Taiwan for decades. We aimed to revisit the role of virulent genotype K1/K2 and possible predisposing factors, compared to our published 2007 cohort., Methods: All adult patients with monomicrobial KPB during 2017 at a medical center in Taiwan were prospectively enrolled. We genotyped the major K types of K. pneumoniae strains, and analyzed the role of prior use of antibiotic or proton pump inhibitor (PPI)., Results: A total of 213 cases were enrolled. Compared to our previous 2007 study (n = 231), there was a higher percentage of patients with community onset bacteremia (75% vs. 60%, p = 0.003). The overall mortality rate was lower in 2017 (23% vs. 32%, p = 0.02), while the rates of antimicrobial resistance (all classes) were higher in 2017. There were 40 cases of liver abscesses in 2017 (19%), with an overall mortality rate of 7.5%. The prevalence of K1 was similar (16% in 2017 vs. 19% in 2007), but the prevalence of K2 decreased significantly (7% in 2017 vs. 17% in 2007, p = 0.001). After excluding 39 cases without data of recent medication use, 48 of 174 (28%) of patients had received a PPI within 90 days. Patients with recent PPI use had more complicated underlying illnesses, higher antimicrobial resistance, and higher in-hospital mortality, but was negatively associated with liver abscess (4% vs. 24%, p = 0.002). Of patients with community-acquired bacteremia, 51% used antibiotics within 90 days. After excluding 37 patients received antibiotics within 14 days before the detection of bacteremia, patient with antibiotic use within 15-90 days had higher Pittsburgh bacteremia scores (4.5 vs. 2.7, p = 0.04), creatinine levels, and frequency of recent surgery, but was not associated with liver abscess (21% vs. 31%, p = 0.33)., Discussion: In summary, after a decade, community onset KPB is still prevalent (1.3 case per 1000 emergency department visit). K1 remains to be the dominant genotype. The association of prior ampicillin/amoxicillin or PPIs use for liver abscess is not confirmed., Competing Interests: Declaration of Competing Interest All authors report no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Background/purpose: The purpose of this study was to determine the pathogens and to estimate the incidence of pediatric community-acquired pneumonia (CAP) in Taiwan., Methods: This prospective study was conducted at eight medical centers from November 2010 to September 2013. Children aged 6 weeks to 18 years who met the radiologic criteria for pneumonia were enrolled. To detect classical and atypical bacteria and viruses, blood and pleural fluids were cultured, and respiratory specimens were examined by multiple conventional and molecular methods., Results: At least one potential pathogen was identified in 705 (68.3%) cases of 1032 children enrolled, including bacteria in 420 (40.7%) cases, virus in 180 (17.4%) cases, and mixed viral-bacterial infection in 105 (10.2%) cases. Streptococcus pneumoniae (31.6%) was the most common pathogen, followed by Mycoplasma pneumoniae (22.6%). Adenovirus (5.9%) was the most common virus. RSV was significantly associated with children aged under 2 years, S. pneumoniae in children aged between 2 and 5 years, and M. pneumoniae in children aged >5 years. The annual incidence rate of hospitalization for CAP was highest in children aged 2-5 years (229.7 per 100,000). From 2011 to 2012, significant reduction in hospitalization rates pertained in children under 5 years of age, in pneumonia caused by pneumococcus, adenovirus or co-infections and complicated pneumonia., Conclusion: CAP related pathogens have changed after increased conjugated pneumococcal vaccination rates. This study described the latest incidences and trends of CAP pathogens, which are crucial for prompt delivery of appropriate therapy., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020. Published by Elsevier B.V.)

Background: The diagnostic cut-off value for chronic pulmonary Aspergillosis (CPA) by Aspergillus fumigatus-specific IgG has never been evaluated In Taiwan. The cut-off value for Aspergillus flavus-specific IgG has not been evaluated worldwide., Objectives: Evaluate diagnostic cut-off value of Aspergillus IgG and its application characteristics., Patients/methods: Blood from control groups and treatment-naïve patients with CPA infections was collected for Aspergillus-specific IgG measurements. Controls were patients who had chest radiographic abnormalities and signs of respiratory tract infection, but were negative for Aspergillus and resolved without anti-mould therapy. Confirmation and probability of CPA were defined according to radiological features and positivity for an Aspergillus or galactomannan index. Chest computer tomography patterns were recorded for the presence of aspergilloma or nodules, subacute invasive aspergillosis, chronic cavitary pulmonary aspergillosis and chronic fibrotic pulmonary aspergillosis., Results: A total of 35 cases and 50 disease controls were included. The levels of A. fumigatus- and A. flavus-specific IgG correlated with CPA progression (P < .05) but not with the presence of Aspergillus species from clinical specimens (P > .05). The best cut-off value for A. fumigatus IgG was 21.7 mg/L with area under curve (AUC) for receiver operating characteristic curve (ROC) 0.934 and had 85.7% sensitivity and 92.0% specificity. For A. flavus IgG, the best cut-off value was 22.1 mgA/L and the AUC was 0.928 with 88.2% sensitivity and 94.1% specificity., Conclusion: The level of Aspergillus-specific IgG correlated with radiographic characteristics in patients with CPA and the best cut-off values compared to controls were 21.7 mgA/L for A. fumigatus-specific IgG and 22.1 mgA/L for A. flavus-specific IgG., (© 2020 Blackwell Verlag GmbH.)

Background: Two rotavirus vaccines (RV1 and RV5) are available on the private market in Taiwan, not included in national immunization program. Scanty reports evaluated the rotavirus vaccine effectiveness (VE) in Asian countries., Methods: From February 2014-July 2017, we conducted a prospective case-control study in ten hospitals in Taiwan. Case-patients included children aged 8-59 months, and hospitalized with laboratory-confirmed rotavirus acute gastroenteritis (AGE). For each case patient, up to four controls, rotavirus-negative AGE or non-AGE illnesses, respectively, were matched by gender, age and enrolled date. Vaccination history was confirmed through vaccination card or hospital record. VE was calculated as (1 - odds ratio of vaccination) × 100%., Results: Totally 4248 AGE patients and 2242 non-AGE controls were enrolled. A total of 330 case-patients with rotavirus AGE, 1226 rotavirus-negative AGE controls and 1122 non-AGE controls were included for analysis. Unvaccinated rate was 85.15% for rotavirus-positive cases, 42.9% for rotavirus-negative controls, and 34.31% for non-AGE controls. VE of two-dose RV1 was 84.9% (95% confidence interval [CI]:77.7%, 90.1%) for rotavirus-negative AGE and 88.9% (95% CI: 83.4%, 92.8%) for non-AGE controls, while VE of three-dose RV5 was 92.5% (95% CI: 85.1%, 96.7%) and 96.4% (95% CI: 91.9%, 98.6%), respectively. For respective vaccine, VEs were not significantly different in term of rotavirus genotypes. VEs of both vaccines declined <80% in children aged three years by combined controls., Conclusions: Both vaccines provided excellent and sustained protection against rotavirus AGE hospitalization in children in Taiwan, but the effectiveness declined slightly in children aged three years., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A multicenter collection of bacteremic isolates of Escherichia coli ( n = 423), Klebsiella pneumoniae ( n = 372), Pseudomonas aeruginosa ( n = 300), and Acinetobacter baumannii complex ( n = 199) was analyzed for susceptibility. Xpert Carba-R assay and sequencing for mcr genes were performed for carbapenem- or colistin-resistant isolates. Nineteen (67.8%) carbapenem-resistant K. pneumoniae ( n = 28) and one (20%) carbapenem-resistant E. coli ( n  = 5) isolate harbored bla KPC ( n = 17), bla OXA-48 ( n  = 2), and bla VIM ( n = 1) genes., (Copyright © 2020 American Society for Microbiology.)

Background: Hymenopteran stings are the most common animal insult injury encountered in the emergency department. With increasing global spread of imported fire ants in recent decades, the rate of Formicidae assault has become a serious problem in many countries. Formicidae-associated injuries gradually increased in Taiwan in recent decades and became the second most common arthropod assault injury in our ED. The present study aimed at comparing the clinical characteristics of Formicidae sting patients with those of the most serious and common group, Vespidae sting patients, in an emergency department (ED) in Taiwan., Methods: This retrospective study included patients who were admitted between 2015 to 2018 to the ED in a local teaching hospital in Taiwan after a Vespidae or Formicidae sting. Cases with anaphylactic reaction were further compared., Results: We reviewed the records of 881 subjects (503 males, 378 females; mean age, 49.09 ± 17.62 years) who visited our emergency department due to Vespidae or Formicidae stings. A total of 538 (61.1%) were categorized into the Vespidae group, and 343 (38.9%) were sorted into the Formicidae group. The Formicidae group had a longer ED length of stay (79.15 ± 92.30 vs. 108.00 ± 96.50 min, p < 0.01), but the Vespidae group had more cases that required hospitalization (1.9% vs. 0.3%, p = 0.04). Antihistamines (76.8% vs. 80.2%, p < 0.01) were more frequently used in the Formicidae group, while analgesics were more frequently used in the Vespidae group (38.1% vs. 12.5%, p < 0.01). The Vespidae group had more local reactions, and the Formicidae group had more extreme, systemic, or anaphylactic allergic reactions. Creatine kinase was significantly higher in the Vespidae group with an anaphylactic reaction. Sting frequency in both groups exhibited the same positive associations with average temperature of the month and weekend days., Conclusion: Formicidae sting patients presented to the ED with higher rate allergic reactions and spent more time in the ED than Vespidae sting patients. However, Vespidae sting patients had more complications and higher rates of admission, especially with anaphylactic reaction. Laboratory data, especially creatine kinase data, were more valuable to check in Vespidae sting patients with an anaphylactic reaction in the ED. Both groups exhibited positive correlations with temperature and a higher rate on weekend days.

Background: Pneumococcal conjugate vaccine (PCV) reduces both invasive pneumococcal disease (IPD) and other pneumococcal infections worldwide. We investigated the impact of stepwise implementation of childhood PCV programs on the prevalence of pneumococcal pneumonia, severity of acute inflammation, and associations between breakthrough pneumonia and pneumococcal serotypes in Taiwan., Methods: In total, 983 children diagnosed with community-acquired pneumococcal pneumonia were enrolled between January 2010 and December 2015., Results: Proportions of pneumococcal vaccinations increased each year in age-stratified groups with PCV7 (32.2%) as the majority, followed by PCV13 (12.2%). The proportion of pneumococcal pneumonia decreased each year in age-stratified groups, especially in 2-5 year group. Serotype 19A is the leading serotype either in vaccinated (6.4%) or unvaccinated patients (5.2%). In particular, vaccinated patients had significantly higher lowest WBC, lower neutrophils, lower lymphocytes and lower CRP values than non-vaccinated patients (p < 0.05). After stratifying patients by breakthrough infection, those with breakthrough pneumococcal infection with vaccine coverage serotypes had more severe pneumonia disease (p < 0.05)., Conclusion: Systematic childhood pneumococcal vaccination reduced the prevalence of community-acquired pneumococcal pneumonia, especially in 2-5 year group. Serotype 19A was the major serotype for all vaccine types in patients with pneumococcal pneumonia and severity of acute inflammatory response was reduced in vaccinated patients.

Objectives: Families are a transmission route for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of the close contact. Monitoring of the viral load will be a valuable method to reduce the optimal number of quarantine days, especially in presymptomatic and symptomatic carriers of their households. The traditional three-generation families living together are seen frequently in East Asia, including in Taiwan., Study Design: We report on a family cluster with six individuals infected with coronavirus disease in Taiwan., Methods: The current public policy in Taiwan is quarantine for at least 14 days, based on the incubation period, or until the patient has tested negative three days in a row using the SARS-CoV-2 reverse transcription polymerase chain reaction. Details on the onset date of clinical symptoms, throat swab conversion, and course of disease were collected from medical records retrospectively., Results: In the household of this three-generation Taiwanese family, the infection rate was 60%. The ratio of males to females was 4:2, and the age range was 11-85 years. The prevalence of asymptomatic disease was 33.3% (2/6). The longest throat swab conversion time was 37 days, and the estimated course of disease from symptoms to first conversion of throat swab was 59 days., Conclusions: Large families, including three-generation families in a single dwelling, should be monitored when the index case is found. Presymptomatic and symptomatic family members could be quarantined for an appropriate duration which, in our experience, is 2 months., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

By the request of the Minister of Health and Welfare, NHRI Biobank was assigned to establish a COVID-19 biobank in early Feb, 2020 to collect COVID-19 patients' blood samples for Taiwan researchers and industries in an emergent way. It was set up in less than 3 weeks and quickly opened for application. By August 5, 2020, this COVID-19 biobank has collected 165 blood samples of 110 patients from more than 10 hospitals across north, middle and south part of Taiwan, including both COVID-19 (+) and (-) pneumonia patients. This biobank can provide applicants with biosamples, such as serum, DNA and RNA, and also the clinical and genomic data, so as to accelerate the COVID-19 treatment and prevention research in Taiwan. This COID-19 biobank already received 15 applications. It has become the most important research resource for the COVID-19 pandemic in Taiwan, including new screening reagents, disease mechanism, the variable human responses and epidemic preventions. Since it is publicly available for both academic and industrial applicants., Competing Interests: Conflicts of interest All authors have no conflicts of interest to declare in this study., (Copyright © 2020 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Objective: COVID-19 has recently become a pandemic affecting many countries worldwide. This study aims to evaluate the current status of COVID-19 in Taiwan and analyze the source of infection., Methods: National data regarding SARS-CoV-2 infection were obtained from Taiwan. CDC at the end of April 2020. These data were subjected to analysis of the current status and correlation between indigenous and imported COVID-19 cases. A phylogenetic tree was created to analyze the phylogeny of Taiwanese SARS-CoV-2 isolates., Results: The first case of SARS-CoV-2 infection in Taiwan was detected on January 21, 2020. Epidemiological data indicate that by April 30, there were a total of 429 COVID-19 confirmed cases with the death rate of 1.3%. Most cases were identified as imported (79.9%; 343/429), with the majority originating from the United States of America (22.1%) and the United Kingdom (17.6%). Results from phylogenetic tree analyses indicate that the Taiwanese SARS-CoV-2 isolates were clustered with the SARS-CoV-2 isolates from other countries (bootstrap value 98%) and sub-clustered with bat SARS-like coronaviruses (bootstrap value 99%)., Conclusion: This study suggests that the importation of SARS-CoV-2 infection was the primary risk-factor resulting in the COVID-19 epidemic in Taiwan., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: This study developed a surveillance system suitable for monitoring epidemic outbreaks and assessing public opinion in non-English-speaking countries. We evaluated whether social media reflects social uneasiness and fear during epidemic outbreaks and natural catastrophes., Design: Cross-sectional study., Setting: Freely available epidemic data in Taiwan., Main Outcome Measure: We used weekly epidemic incidence data obtained from the Taiwan Centers for Disease Control and online search query data obtained from Google Trends between 4 October 2015 and 2 April 2016. To validate whether non-English query keywords were useful surveillance tools, we estimated the correlation between online query data and epidemic incidence in Taiwan., Results: With our approach, we noted that keywords ('common cold'), ('fever') and ('cough') exhibited good to excellent correlation between Google Trends query data and influenza incidence (r=0.898, p<0.001; r=0.773, p<0.001; r=0.796, p<0.001, respectively). They also displayed high correlation with influenza-like illness emergencies (r=0.900, p<0.001; r=0.802, p<0.001; r=0.886, p<0.001, respectively) and outpatient visits (r=0.889, p<0.001; r=0.791, p<0.001; r=0.870, p<0.001, respectively). We noted that the query ('enterovirus') exhibited excellent correlation with the number of enterovirus-infected patients in emergency departments (r=0.914, p<0.001)., Conclusions: These results suggested that Google Trends can be a good surveillance tool for epidemic outbreaks, even in Taiwan, the non-English-speaking country. Online search activity indicates that people are concerned about epidemic diseases, even if they do not visit hospitals. This prompted us to develop useful tools to monitor social media during an epidemic because such media usage reflects infectious disease trends more quickly than does traditional reporting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study was performed to examine the current status of Zika and the effects of pre-existing dengue immunity on Zika virus (ZIKV) infection in Southern Taiwan., Methods: A phylogenetic tree was used to analyze the phylogeny of detected ZIKVs. Paired sera from dengue patients were collected for the determination of dengue and Zika infection. Plaque reduction neutralization tests (PRNT) and quantitative reverse transcription PCR (qRT-PCR) were used to determine the titers of neutralizing antibodies and viruses, respectively. An antibody-dependent enhancement (ADE) assay was used to evaluate the effect of anti-dengue antibodies on ZIKV infection., Results: Epidemiological data indicated the continuous importation of ZIKV infection from neighboring Zika epidemic countries into Taiwan. A total of 78 dengue patients were enrolled and 21 paired serum samples were obtained. PRNT 90 results for the 21 samples identified eight cases of primary dengue infection and 13 cases of secondary dengue infection; two samples were positive for ZIKV (MR766). Results from the ADE assay indicated that convalescent sera from primary and secondary dengue infection patients displayed significant ADE of the ZIKV infection when compared to healthy controls (p < 0.05)., Conclusions: This study suggests that pre-existing dengue immunity facilitates ZIKV infection and that the continuous importation of ZIKV infection may pose a threat to indigenous Zika emergence in Southern Taiwan., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

There are limited studies on the association between systemic autoimmune rheumatic diseases (SARDs) and leptospirosis. Therefore, this study aims to identify the effects of leptospirosis on the risks of developing SARDs with a nationwide retrospective cohort study. Patients with leptospirosis who did not have a diagnosis of SARDs before the index date were enrolled from the Taiwan National Health Insurance Research Database between 2000 and 2010, as the leptospirosis cohort. For each patient with leptospirosis, one control without a history of leptospirosis and SARDs was randomly selected (non-leptospirosis cohort). Cox proportional hazards regression models were used to analyze the risk of SARDs according to sex, age, and comorbidities. Among the 23 million people in the cohort, 3,393 patients with leptospirosis (68.91% men, mean age 52.65 years) and 33,930 controls were followed for 18,778 and 232,999 person-years, respectively. The incidence of SARDs was higher in the leptospirosis cohort than in the non-leptospirosis cohort (1.38 vs 0.33 per 1000 person-years), with a hazard ratio (HR) of 4.42 (95% confidence interval [CI] = 2.82-6.92). The risk of developing SARDs was highest for leptospirosis patients aged ≥65 years (HR = 2.81% CI = 1.07-7.36) compared with patients aged ≤39 years. Patients with leptospirosis have a 4.42-fold higher risk of SARDs than that in the general population. Further research is warranted to investigate the mechanism underlying this association.

Background/purpose: This study was aimed to investigate clinical characteristics and treatment outcomes of pulmonary invasive fungal infection (IFI) among patients with hematological malignancy., Methods: All patients with hematological malignancy who were treated at a medical centre from 2008 to 2013 were evaluated. Pulmonary IFI was classified according to the European Organization for Research and Treatment of Cancer 2008 consensus., Results: During the study period, 236 (11.3%) of 2083 patients with hematological malignancy were diagnosed as pulmonary IFI, including 41 (17.4%) proven, 75 (31.8%) probable, and 120 (50.8%) possible cases. Among the 116 patients of proven and probable cases of pulmonary IFI, aspergillosis alone (n = 90, 77.6%) was predominant, followed by cryptococcosis alone (n = 9, 7.8%), and mucormycosis (n = 4, 3.4%). The overall incidence of patients with pulmonary IFI was 5.9 per 100 patient-years. The highest incidence (per 100 patient-year) was found in patients with acute myeloid leukaemia (13.7) followed by acute lymphoblastic leukaemia (11.3), and myelodysplastic syndrome/severe aplastic anaemia (6.7). Fourteen (5.9%) of the 236 patients with pulmonary IFI died within 12 weeks after diagnosis of pulmonary IFI. Univariate analysis revealed that elderly age (>65 years) (P = 0.034), lack of response to anti-fungal treatment (P < 0.001), and admission to the intensive care unit (ICU) (P < 0.001) were predictors of poor prognosis. However, only admission to the ICU was an independent predictor of poor prognosis for 12-week mortality (P = 0.022) based on multivariate analysis., Conclusion: Patients with acute leukaemia and myelodysplastic syndrome/severe aplastic anaemia were at high risk of pulmonary IFI., (Copyright © 2018. Published by Elsevier B.V.)

Background: Influenza is a major cause of acute respiratory infection burden worldwide, leading to many hospitalizations. An annual influenza vaccine is believed to be the best way to prevent influenza-related illnesses. We focused on the efficacies of other possible preventive measures such as increasing sun exposure time and dietary supplements to prevent these illnesses., Methods: We conducted a matched-pair case-control study along with the Taiwan Pediatric Infectious Disease Alliance. We included influenza-related hospitalized patients with age ranging from 6 months to 5 years during the 2012-2013, 2013-2014, 2014-2015, and 2015-2016 influenza seasons. The controls were comparable to cases in age, sex, and residential area and had no influenza-related hospitalization records in the same season. We extracted data from vaccination histories and got the patients' guardians to complete questionnaires. Data were analyzed using conditional logistic regression., Results: We enrolled 1514 children (421 influenza-infected cases and 1093 controls) in the study. We found seasonal influenza vaccination to be an independent protective factor against hospitalizations owing to influenza [p < 0.01; odds ratio (OR), 0.427; 95% confidence interval (CI), 0.306-0.594]. Children with mean sun exposure time of >7 h/week had a significantly lower risk of influenza-related hospitalizations than those with the mean sun exposure time of ≤7 h/week (p < 0.05; OR, 0.667; 95% CI, 0.491-0.906)., Conclusions: Seasonal influenza vaccination effectively prevents influenza-related hospitalizations in children aged ≤5 years. Besides, >7 h of sun exposure/week may also be associated with lower risk of influenza-related hospitalizations in children., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: The aim of this study was to determine the long-term incidence of cryptococcosis in kidney transplant recipients (KTRs) and to analyze its risk factors., Methods: This retrospective population-based cohort study analyzed data obtained from Taiwan's National Health Insurance Research Database for KTRs during 2000-2012 and matched cohorts. Both populations were followed until death, development of cryptococcosis, or December 2013., Results: A total of 4,933 KTRs and 49,930 matched patients were included. The cryptococcosis incidence rates for the KTR cohort and matched cohort were 10.59 and 0.4 per 10,000 person-years, respectively. The hazard ratio for cryptococcosis among KTRs was 26.65 (p<0.001); and 43.77 (p<0.001) for cryptococcosis affecting the central nervous system (CNS). The Kaplan-Meier method confirmed an elevated cumulative incidence of cryptococcosis among KTRs (1.00% vs. 0.04%). Predictors for cryptococcosis were advanced age (OR 1.39, 95% CI 1.02-1.89, P=0.038) and cancer (OR 2.63, 95% CI 1.22-5.67, P=0.013), but not the use of any particular class of immunosuppressants., Conclusions: KTRs are at dramatically higher risk of developing cryptococcosis, especially with CNS involvement, relative to a non-KTR matched cohort. Older KTRs and those with cancer are at even higher risk of developing cryptococcosis., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study examined the epidemiological, clinical, and immunological characteristics of the 2015 dengue outbreak in Taiwan., Methods: Clinical data were collected from dengue fever (DF) and dengue hemorrhagic fever (DHF) patients. A phylogenetic tree was used to analyze the source of the outbreak strain. Paired plasma samples from DF/DHF patients were used for antibody-dependent enhancement (ADE) assay and cytokine multiplex biometric immunoassay to validate the immunological mechanism., Results: This outbreak mainly occurred in two of the southern cities of Taiwan: Tainan (n=22 777; 52%) and Kaohsiung (n=19 784; 45%). A high DHF death rate was noted (34.6%). The case (DHF) and control (DF) study indicated that older age (>60 years), type II diabetes, and hypertension were risk factors correlated with the development of DHF (p< 0.0001). The phylogenetic tree results suggested that the outbreak-associated strain was dengue virus serotype 2 and cosmopolitan genotype, forming a stable cluster with the isolates from Thailand and Indonesia (bootstrap value of 99%). Cytokine analyses demonstrated that levels of interleukin (IL)-6, IL-4, IL-13, IL-1β, interferon gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly higher in DHF patients compared to DF patients (p< 0.001). The ADE assay showed that diluted plasma containing preexisting dengue antibodies from DHF patients significantly enhanced dengue infection (p< 0.05)., Conclusion: The results suggest that older age, type II diabetes, hypertension, immunological cytokine dysregulation, and preexisting dengue antibodies inducing ADE infection are correlated with dengue severity. This study also indicates that the largest dengue outbreak in Taiwan might have been a result of imported DF from dengue epidemic regions., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Iliopsoas abscess (IPA) is a rare clinical entity and is difficult to diagnose due to its insidious onset and nonspecific symptoms. The association between IPA and cardiovascular disorders (CVD) has been rarely reported. Computed tomographic (CT) scan can provide a definitive diagnosis of IPA and associated foci of adjacent structures. IPA is a life-threatening condition, especially when associated with CVD., Materials and Methods: We conducted a hospital-based observational study of IPA associated with CVD. Data were collected from the electronic clinical database of Taichung Veterans General Hospital (1520-bed tertiary referral hospital in central Taiwan) between July 2007 and December 2017. The diagnosis of IPA associated with CVD was confirmed by classical findings on CT and transesophageal echocardiography with compatible clinical presentation and cultures from pus/tissue and blood., Results: Fifteen patients of IPA associated with CVD were studied. They included 12 males (80%) and 3 females (20%), with a mean age 63.2 ± 16.9 years (31-85 years). CVD included stent-graft/endograft infection of abdominal aortic aneurysm (AAA) (40%), primary mycotic AAA (33.3%), and infective endocarditis (26.7%). Staphylococcus aureus is the most common microorganism in pus/tissue cultures (n = 3, 37.5%) and in blood cultures (n = 6, 40%). The average length of hospital stay was 33.1 ± 20.5 days (range, 3-81 days; median, 33 days). Hospital stay lasted 42.6 ± 19.2 days in the survival group and 19.0 ± 14.1 days (P = 0.018) in the non-survival group. Incidence of patients staying in the intensive care unit (ICU) with intubation > 3 days was 33% in the survival group and 100% (P = 0.028) in the non-survival group. Intra-hospital mortality rate was 40%. Poor prognostic factors in the non-survival group were hypoalbuminemia, hyponatremia, involved disc/vertebral body and/or epidural abscess, and ICU stay with intubation > 3 days. Cumulative survival rate was 25% under conservative treatments and 66.3% under aggressive treatments (P = 0.038)., Conclusion: Due to high mortality rates, clinicians should keep a high suspicion index for IPA associated with CVD through clinical presentation, physical examination, and imaging study. Timely empiric antibiotics for common bacteria, drainage for IPA, endovascular repair, or vascular reconstruction by graft replacement or bypass with intensive care should be mandatory to shorten the hospital stay, reduce medical costs, and lower mortality rate.

Background/purpose: This study investigated the impact of implementing ventilator-associated pneumonia (VAP) bundle care on the rates of VAP in intensive care units (ICUs) in Taiwan., Methods: A total of 10 ICUs (bed number, 170), including surgical (SICUs) (n = 7), cardiovascular/surgical (CV/S-ICUs) (n = 1), and medical ICUs (MICUs) (n = 2) from 10 hospitals (7 medical center hospitals and 3 regional hospitals) were enrolled in this quality-improvement project. This study was divided into the pre-intervention phase (1st January, 2012-31st July, 2013) and the intervention phase (1st August, 2013-31st October, 2014)., Results: Among the 10 hospitals, the overall rates (cases per 1000 ventilator-days) of VAP declined significantly (p = 0.005; rate ratio, 0.71) from 1.9 in the pre-intervention period to 1.5 in the intervention period. Significant difference in VAP rates between these periods was found in the regional hospitals (from 1.6 to 0.7; p < 0.001) and the SICUs (from 2.1 to 1.4; p < 0.001), but not in the medical centers (2.0 vs. 1.9; p = 0.0667) or CV/S-ICUs (4.5 vs. 4.5; p = 0.5391). However, VAP rate increased significantly (cases per 1000 ventilator-days) in the MICUs between the two periods (from 0.5 to 1.0; p = 0.0489). For the VAP bundle care elements, the overall compliance rate was 87.7% with 83.6% and 97.9% in the medical centers and regional hospitals, respectively., Conclusions: Implementing VAP bundle care has effectively reduced VAP in Taiwanese ICUs, but differences in performance and compliance rates of VAP bundle care among the different ICUs and hospital categories did exist., (Copyright © 2017. Published by Elsevier B.V.)

Background: The outcomes of deep-seated abscesses attributed to chronic disseminated candidiasis (CDC) in patients with hematological malignancies have rarely been reported in recent years., Methods: We retrospectively reviewed and analyzed the data of patients with hematological malignancies who received a diagnosis of CDC at a medical center in Taiwan between 2008 and 2013., Results: Sixty-one patients (32 men and 29 women) were diagnosed with CDC. The median age was 51 years (range: 18-83). The overall incidence of CDC was 1.53 per 100 patient-years in patients with hematological malignancies between 2008 and 2013. The highest incidence of CDC was 4.3 per 100 patient-years for acute lymphoblastic leukemia, followed by 3.6 for acute myeloid leukemia. We detected 3 (4.9%) proven, 13 (21.3%) probable, and 45 (73.8%) possible cases of CDC. A total of 13 patients had positive blood cultures for Candida species: C. tropicalis (8), C. albicans (2), C. glabrata (2), and C. famata (1). The median duration of antifungal treatment was 96 days (range: 7-796 days). Serial imaging studies revealed that the resolution rate of CDC was 30.0% at 3 months and 54.3% at 6 months. Five patients (8.2%) had residual lesions that persisted beyond one year. A multivariate analysis of the 90-day outcome revealed that shock was the only independent prognostic factor of 90-day survival in patients with CDC., Conclusion: The incidence of CDC did not decrease between 2008 and 2013. Patients with acute leukemia had a higher risk of CDC than those with other hematological malignancies. Imaging studies conducted at 6 months after diagnosis revealed that only half of the patients showed complete resolution. CDC requires prolonged treatment, and serial imaging at 6 months interval is suggested. Shock is the only independent prognostic factor of 90-day survival in patients with CDC.

Background: Acute diarrhea is a major cause of childhood morbidity and an economic burden for families. The aim of this study is to explore the effect of probiotics on clinical symptoms, intestinal microbiota, and inflammatory markers during childhood diarrhea., Methods: Children ( n = 81) aged six months to six years (mean age 2.31 years) hospitalized for acute diarrhea were randomized to receive probiotics ( Lactobacillus casei variety rhamnosus ; n = 42) or no probiotics ( n = 39) orally twice daily for seven days. Feces samples were also collected to evaluate microbial content using a traditional agar plate and next-generation sequencing. Immunoglobulin A (IgA), lactoferrin, and calprotectin were determined by enzyme-linked immunosorbent assay (ELISA) and compared in different groups. Other clinical symptoms or signs, including fever, vomiting, diarrhea, abdominal pain, bloated abdomen, daily intake, appetite, and body weight were also assessed., Results: Data were collected from 81 individuals across three different time points. Total fecal IgA levels in fecal extracts of the probiotics group were higher than those in the control group, reaching statistical significance ( p < 0.05). Concentrations of fecal lactoferrin and calprotectin were significantly downregulated in patients with probiotic Lactobacillus casei variety rhamnosus (Lc) consumption compared to those of the control ( p < 0.05). Probiotic Lc administration may be beneficial for gut-microbiota modulation, as shown by the data collected at one week after enrollment. Counts of Bifidobacteria and Lactobacillus species were elevated in stool culture of the probiotic group. Appetite and oral intake, body-weight gain, abdominal pain, bloating, as well as bowel habits (diarrhea) were much better in children receiving probiotics compared with those in the control group., Conclusion: Fecal IgA increased during acute diarrhea under Lc treatment; in contrast, fecal lactoferrin and calprotectin were downregulated during acute diarrhea under Lc treatment. Probiotic Lc may be a useful supplement for application in children during acute diarrhea to reduce clinical severity and intestinal inflammatory reaction.

To determine the incidence and risk of Parkinson disease (PD) in patients with Sjögren syndrome (SS) according to a nationwide population-based database.In total, 12,640 patients in the SS cohort and 50,560 in the non-SS cohort were enrolled from Taiwan's National Health Insurance Research Database from 2000 to 2010. We used the Cox multivariable proportional hazards model to determine the risk factors for PD in the SS cohort.We observed an increased incidence of PD in patients with SS, with a crude hazard ratio (HR) of 1.40 and an adjusted HR (aHR) of 1.23. The cumulative incidence of PD was 1.95% higher in the SS cohort than in the non-SS cohort. The SS cohort had an elevated HR under medication use, namely cevimeline and pilocarpine (crude HR, 1.28), hydroxychloroquine (crude HR, 1.43; aHR, 1.46), and methylprednisolone (crude HR, 2.21; aHR, 1.49). Patients receiving other non-hydroxychloroquine immunosuppressant therapies had a lower risk (aHR, 0.86) of PD. Furthermore, patients with SS aged 20 to 49 years had a 1.93-fold higher risk of PD than did those without SS (aHR, 1.93). The risk of PD was higher (aHR, 2.20) in patients with SS without comorbidities than in those with comorbidities. The aHR of PD significantly increased when the follow-up period exceeded 9 years (aHR, 1.93).We determined an increased risk of PD in patients with SS. Further investigation is warranted to determine the possible underlying mechanisms and the potential role of non-hydroxychloroquine immunosuppressants in ameliorating PD.

Objectives: We investigated the in vitro activities of cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam and other related drugs against imipenem-resistant Pseudomonas aeruginosa, imipenem-resistant Acinetobacter baumannii and Stenotrophomonas maltophilia isolates., Methods: Non-duplicated bacteraemia isolates (n = 300) of imipenem-resistant P. aeruginosa (n = 100), imipenem-resistant A. baumannii (n = 100) and S. maltophilia (n = 100) were evaluated. Imipenem-resistant P. aeruginosa and imipenem-resistant A. baumannii isolates were defined as isolates exhibiting imipenem MIC ≥8 mg/L, as determined using the VITEK 2 system. The MICs of 11 other antimicrobial agents for the isolates were determined by the broth microdilution method. Iron-depleted CAMHB was used to determine the MICs of cefiderocol., Results: The rates of colistin resistance of imipenem-resistant P. aeruginosa and imipenem-resistant A. baumannii were 5% and 10%, respectively. The MIC90 values of cefiderocol, ceftolozane/tazobactam, ceftazidime/avibactam, tigecycline and colistin were as follows: imipenem-resistant P. aeruginosa: 1, 4, 16, >4 and 2 mg/L; imipenem-resistant A. baumannii: 8, >64, >64, 4 and 2 mg/L; and S. maltophilia: 0.25, >64, >64, 2 and >8 mg/L, respectively. For imipenem-resistant A. baumannii isolates, the MICs of cefiderocol, ceftolozane/tazobactam and ceftazidime/avibactam were ≤4 mg/L for 88%, 8% and 1% of the isolates, respectively. Cefiderocol MICs were ≤4 mg/L for the five colistin-resistant imipenem-resistant P. aeruginosa isolates and 70% of the 10 colistin-resistant imipenem-resistant A. baumannii isolates., Conclusions: Cefiderocol exhibited more potent in vitro activity than ceftolozane/tazobactam and ceftazidime/avibactam against imipenem-resistant P. aeruginosa, imipenem-resistant A. baumannii and S. maltophilia isolates.

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., (Copyright © 2017. Published by Elsevier B.V.)

Background: Active tuberculosis (TB) in patients with latent tuberculosis infection (LTBI) was associated with use of biological agents for immune-mediated inflammatory disorders (IMIDs). For decreasing active TB, isoniazid prophylaxis therapy was administered before biologic therapy among IMID patients with LTBI. However, for patients who had been received biologics for a long time with unknown status of LTBI or exposure history of active TB, the prevalence of LTBI and efficacy of isoniazid therapy were unclear., Method: A retrospective cohort study was conducted during 2012-2014 in a tertiary medical center in Taiwan, and the incidence case of active TB was identified by the national TB registration system on October 1, 2015., Results: All 382 patients with 1532 person-years were followed up, the initial prevalence of LTBI by positive interferon-gamma releasing assay (IGRA+) was 17.5%. The prevalence of LTBI was increased in elder age (>20%, p < 0.05), chronic kidney disease (33%, p < 0.05), metabolic syndrome (26.3%, p < 0.05), but not related to the type of IMIDs or biologics. The crude incidences of TB were increased in elders (53.3/1000 person-year), abnormal chest film (49.6/1000 person-year), administration of tocilizumab (13.6/1000 person-year), and metabolic syndrome (56.1/1000 person-year), respectively. Among patents with LTBI, the incidence of active TB was lower in patients with isoniazid therapy (9.2/1000 person-year, p = 0.02) than without isoniazid therapy (92.2/1000 person-years), regardless the timing of initiating isoniazid therapy (p > 0.05)., Conclusion: Isoniazid therapy can prevent active TB from LTBI despite of the timing of biologics administration., (Copyright © 2017. Published by Elsevier B.V.)

Objectives: This study aimed to investigate antibiotic prescribing patterns and effectiveness of different anti-carbapenem-resistant Acinetobacter baumannii (CRAB) strategies for CRAB pneumonia., Methods: We conducted a multicentre, retrospective study in three hospitals. During 2010-2015, adult ICU patients with CRAB pneumonia treated with at least one antimicrobial agent covering the CRAB isolate in vitro for more than 2 days were included. We used multivariate logistic regression to analyse the associations of anti-CRAB strategies with ICU mortality and other clinical outcomes., Results: Among 238 patients with CRAB pneumonia, tigecycline monotherapy (84, 35.3%) was the most common antibiotic strategy, followed by tigecycline with colistin (43, 18.1%), colistin monotherapy (34, 14.3%), colistin combination without tigecycline (33, 13.9%), tigecycline combination without colistin (32, 13.4%), and sulbactam-based therapy without tigecycline and colistin (12, 5.0%). In multivariate analysis, tigecycline-based therapy was associated with higher ICU mortality than non-tigecycline therapy (adjusted OR 2.30, 95% CI 1.19-4.46). There was no difference between colistin-based therapy and non-colistin therapy. Compared with tigecycline monotherapy, colistin monotherapy was associated with lower ICU mortality (aOR 0.30, 95% CI 0.10-0.88). Treatment failure analyses showed similar trends. Tigecycline-based therapy was associated with higher treatment failure rate than non-tigecycline therapy (aOR 2.51, 95% CI 1.39-4.54), whereas colistin-based therapy was associated with lower treatment failure rate than non-colistin-based therapy (aOR 0.48, 95% CI 0.27-0.86)., Conclusions: Tigecycline was commonly prescribed for CRAB pneumonia. However, tigecycline-based therapy was associated with higher ICU mortality and treatment failure. Our study suggests that colistin monotherapy may be a better antibiotic strategy for CRAB pneumonia., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)