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AbstractActinobacillus pleuropneumoniae infection causes a high mortality rate in porcine animals. Antimicrobial resistance poses global threats to public health. The current study aimed to determine the antimicrobial susceptibilities and probe the resistome of A. pleuropneumoniae in Taiwan. Herein, 133 isolates were retrospectively collected; upon initial screening, 38 samples were subjected to next-generation sequencing (NGS). Over the period 2017–2022, the lowest frequencies of resistant isolates were found for ceftiofur, cephalexin, cephalothin, and enrofloxacin, while the highest frequencies of resistant isolates were found for oxytetracycline, streptomycin, doxycycline, ampicillin, amoxicillin, kanamycin, and florfenicol. Furthermore, most isolates (71.4%) showed multiple drug resistance. NGS-based resistome analysis revealed aminoglycoside- and tetracycline-related genes at the highest prevalence, followed by genes related to beta-lactam, sulfamethoxazole, florphenicol, and macrolide. A plasmid replicon (repUS47) and insertion sequences (IS10R and ISVAp11) were identified in resistant isolates. Notably, the multiple resistance roles of the insertion sequence IS10R were widely proposed in human medicine; however, this is the first time IS10R has been reported in veterinary medicine. Concordance analysis revealed a high consistency of phenotypic and genotypic susceptibility to florphenicol, tilmicosin, doxycycline, and oxytetracycline. The current study reports the antimicrobial characterization of A. pleuropneumoniae for the first time in Taiwan using NGS.

Abstract Background Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD). Methods This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry. Results Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1β, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (−), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (−) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. Conclusion Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO.

This study investigated antimicrobial resistance in Salmonella enterica serovar Choleraesuis (S. Choleraesuis) isolates from diseased pigs in Taiwan (2015–2020). Among 272 isolates, florfenicol (96.7%), enrofloxacin (96.3%), doxycycline (91.2%), gentamicin (84.6%), and tiamulin (80.5%) exhibited high resistance. 99.3% of the isolates were resistant to at least one antibiotic, and 97.8% of the isolates were multidrug resistant. This study illustrated that S. Choleraesuis isolates exhibited high resistance to antimicrobials currently used in the Taiwanese swine industry.

The burden of respiratory syncytial virus (RSV) infection among older adults in Taiwan is not well understood due to a scarcity of published epidemiological data. Nonetheless, the increasing proportion of older adults is anticipated to translate to increased burden of RSV infection, presenting a challenge to the healthcare system. Thus, an expert meeting was convened among a panel of infectious disease specialists from Taiwan to evaluate the existing local evidence and data gaps related to RSV infection in older adults (aged ≥50 years), and propose steps to generating evidence on disease burden among this population. Overall, there are few studies on the clinical and economic burden of RSV infection in Taiwan, and existing data are limited by small sample sizes and highly selected populations. Inconsistent RSV testing practices among older adults contribute to under-diagnosis and under-reporting, driven by limitations to reimbursement policies that discourage proactive RSV testing in older adults, and the lack of appropriate, targeted RSV treatment. Crucially, the paucity of epidemiological data may perpetuate a lack of awareness of RSV among clinicians and the public, hinder investments into RSV testing at a policymaker level, and thereby impede implementation of consistent diagnostic practices, precluding a deeper understanding of RSV. To overcome these challenges, it is imperative to prioritize generation of epidemiological data to establish the burden of RSV infection among older adults in Taiwan. Such data would also support a multi-stakeholder group in assessing the impact of future RSV-related interventions, such as educational initiatives and preventative strategies including vaccines.

Background: The increasing prevalence of drug-resistant pathogens leads to delays in adequate antimicrobial treatment in intensive care units (ICU). The real-world influence of the BioFire FilmArray Blood Culture Identification 2 (BCID2) panel on pathogen identification, diagnostic concordance with conventional culture methods, and antimicrobial stewardship in the ICU remains unexplored. Methods: This retrospective observational study, conducted from July 2021 to August 2023, involved adult ICU patients with positive blood cultures who underwent BCID2 testing. The concordance between BCID2 and conventional culture results was examined, and its impact on antimicrobial stewardship was assessed through a comprehensive retrospective review of patient records by intensivists. Results: A total of 129 blood specimens from 113 patients were analysed. Among these patients, a high proportion of drug-resistant strains were noted, including carbapenem-resistant Klebsiella pneumoniae (CRKP) (57.1%), carbapenem-resistant Acinetobacter calcoaceticus-baumannii complex (100%), methicillin-resistant Staphylococcus aureus (MRSA) (70%), and vancomycin-resistant Enterococcus faecium (VRE) (100%). The time from blood culture collection to obtaining BCID2 results was significantly shorter than conventional culture (46.2 h vs. 86.9 h, p

Background: The optimal timing for applying the BioFire FilmArray Pneumonia Panel (FAPP) in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) remains undefined, and there are limited data on its impact on antimicrobial stewardship. Methods: This retrospective study was conducted at a referral hospital in Taiwan from November 2019 to October 2022. Adult ICU patients with HAP/VAP who underwent FAPP testing were enrolled. Patient data, FAPP results, conventional microbiological testing results, and the real-world impact of FAPP results on antimicrobial therapy adjustments were assessed. Logistic regression was used to determine the predictive factors for bacterial detection by FAPP. Results: Among 592 respiratory specimens, including 564 (95.3%) endotracheal aspirate specimens, 19 (3.2%) expectorated sputum specimens and 9 (1.5%) bronchoalveolar lavage specimens, from 467 patients with HAP/VAP, FAPP testing yielded 368 (62.2%) positive results. Independent predictors for positive bacterial detection by FAPP included prolonged hospital stay (odds ratio [OR], 3.14), recent admissions (OR, 1.59), elevated C-reactive protein levels (OR, 1.85), Acute Physiology and Chronic Health Evaluation II scores (OR, 1.58), and septic shock (OR, 1.79). Approximately 50% of antimicrobial therapy for infections caused by Gram-negative bacteria and 58.4% for Gram-positive bacteria were adjusted or confirmed after obtaining FAPP results. Conclusions: This study identified several factors predicting bacterial detection by FAPP in critically ill patients with HAP/VAP. More than 50% real-world clinical practices were adjusted or confirmed based on the FAPP results. Clinical algorithms for the use of FAPP and antimicrobial stewardship guidelines may further enhance its benefits.

Background: The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales. Methods: This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and β-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018–2019) and during the COVID-19 pandemic (2020–2021). Results: A total of 1231 Enterobacterales isolates were collected, predominantly Escherichia coli (55.6%) and Klebsiella pneumoniae (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, p

Background: There is a lack of information regarding outcomes of elderly patients hospitalized with COVID-19 following the widespread use of COVID-19 vaccines and antiviral agents. Methods: A retrospective study was conducted between January and August 2022, enrolling patients aged 65 years or older. Patients were categorized into two groups: ‘old’ (65–79 years) and ‘oldest-old’ (80 years or more). Multivariate regression was employed to identify independent prognostic factors for in-hospital mortality. Results: A total of 797 patients were enrolled, including 428 old and 369 oldest-old patients. In each subgroup, 66.6 % and 59.6 % of patients received at least one dose of the COVID-19 vaccine, respectively. Approximately 40 % of the patients received oral antiviral agents either before or upon hospital admission. A greater percentage of the oldest-old patients received remdesivir (53.4 % versus 39.7 %, p

Background: Liver dysfunction is common during coronavirus disease 2019 (COVID-19), while its clinical impact and association with chronic hepatitis B (CHB) remain uncertain. We aimed to investigate liver dysfunction in COVID-19 patients and its impacts on those with/without CHB. Methods: We conducted a retrospective cohort study of COVID-19 patients at National Taiwan University Hospital, stratified according to hepatitis B surface antigen (HBsAg) serostatus, with demographics, laboratory data, and hospitalization course reviewed, and clinical outcomes compared through multivariable analyses. Results: We enrolled 109 COVID-19 patients unvaccinated against SARS-CoV-2 by August 2021. The HBsAg-positive group (n = 34) had significantly higher alanine aminotransferase (ALT) (26 vs. 16 U/L, P = 0.034), platelet (224 vs. 183 k/μL, P = 0.010) and longer hospitalizations (17 vs. 13 days, P = 0.012) compared with HBsAg-negative group (n = 75), while percentages of hepatitis (2-fold ALT elevation), oxygen supplementation, ventilators usage, COVID-specific treatment, intensive care unit (ICU) admission and mortality were comparable. Older age (odds ratio [OR]: 1.04, 95 % confidence interval [CI]: 1.00–1.08, P = 0.032) and higher aspartate aminotransferase (AST) (OR: 1.08, 95 % CI: 1.004–1.16, P = 0.038) were associated with oxygen supplementation according to multivariable analyses. Higher AST predicted ICU admission (OR: 1.11, 95 % CI: 1.03–1.19, P = 0.008). Oxygen usage (OR: 5.64, 95 % CI: 1.67–19.09, P = 0.005) and shock (OR: 5.12, 95 % CI: 1.14–22.91, P = 0.033) were associated with liver dysfunction. Conclusions: CHB patients had higher ALT levels and longer hospitalizations during COVID-19. Higher AST levels predict severe COVID-19 and ICU admission.

Among the 14 patients with respiratory syncytial virus pneumonia, the majority (n = 8, 57.1 %) were older than 65 years and had health care-associated pneumonia (57.1 %). Over 70 % (n = 10) of them exhibited bacterial co-infection, with a high proportion (64.3 %) requiring mechanical ventilation. The hospital mortality rate was 50 %.

Objectives: The FilmArray gastrointestinal panel (FAGIP) is widely used to detect infectious diarrhoea due to its outstanding sensitivity compared to conventional methods, but there is geographic variation, such as in the distribution of pathogens, among populations. Methods: This was a retrospective study that analysed patients with acute diarrhoea who underwent FAGIP tests from all age groups during 2022. We compared positive rates of FAGIP between paediatric (n = 245) and adult patients (n = 242) of different origins. The targeted therapy rate and antimicrobial agent use rate were also analysed. Results: Among the 487 stool samples evaluated, the overall, community-origin (CO), and nosocomial (NC) positivity rates of paediatric patients were significantly higher than those of adults (73.9 % vs. 43.0 %, p = 0.000; 76.2 % vs. 51.7 %, p = 0.000; 50.0 % vs. 19.7 %, p = 0.000). Salmonella was the most frequently detected pathogen (35.9 %) in children, while the predominant pathogen in adult patients was toxin A/B-genic Clostridioides difficile (13.2 %). There was a significantly lower antimicrobial agent use rate after FAGIP results were available (79.1 % vs. 64.5 %, p = 0.000) and a higher rate of targeted therapy towards C. difficile infection in adults than in children (84.4 % vs. 69.0 %, p = 0.011). Conclusion: Paediatric diarrhoea patients showed higher positivity rates than adult patients. Application of FAGIP for acute diarrhoea might lower unnecessary antimicrobial use.

Abstract Background To date, most countries lifted the restriction requirement and coexisted with SARS-CoV-2. Thus, dietary behavior for preventing SARS-CoV-2 infection becomes an interesting issue on a daily basis. Coffee consumption is connected with reduced COVID-19 risk and correlated to COVID-19 severity. However, the mechanisms of coffee for the reduction of COVID-19 risk are still unclear. Results Here, we identified that coffee can inhibit multiple variants of the SARS-CoV-2 infection by restraining the binding of the SARS-CoV-2 spike protein to human angiotensin-converting enzyme 2 (ACE2), and reducing transmembrane serine protease 2 (TMPRSS2) and cathepsin L (CTSL) activity. Then, we used the method of "Here" (HRMS-exploring-recombination-examining) and found that isochlorogenic acid A, B, and C of coffee ingredients showed their potential to inhibit SARS-CoV-2 infection (inhibitory efficiency 43–54%). In addition, decaffeinated coffee still preserves inhibitory activity against SARS-CoV-2. Finally, in a human trial of 64 subjects, we identified that coffee consumption (approximately 1–2 cups/day) is sufficient to inhibit infection of multiple variants of SARS-CoV-2 entry, suggesting coffee could be a dietary strategy to prevent SARS-CoV2 infection. Conclusions This study verified moderate coffee consumption, including decaffeination, can provide a new guideline for the prevention of SARS-CoV-2. Based on the results, we also suggest a coffee-drinking plan for people to prevent infection in the post-COVID-19 era.

Background: Patients with chronic kidney disease are at high risk for coronavirus disease 2019. Little is known about immune response to severe acute respiratory syndrome coronavirus 2 vaccination in patients on peritoneal dialysis (PD). Method: We prospectively enrolled 306 PD patients receiving two doses of vaccines (ChAdOx1-S: 283, mRNA-1273: 23) from July 2021 at a medical center. Humeral and cellular immune responses were assessed by anti-spike IgG concentration and blood T cell interferon-γ production 30 days after vaccination. Antibody ≥0.8 U/mL and interferon-γ ≥ 100 mIU/mL were defined as positive. Antibody was also measured in 604 non-dialysis volunteers (ChAdOx1-S: 244, mRNA-1273: 360) for comparison. Result: PD patients had less adverse events after vaccinations than volunteers. After the first dose of vaccine, the median antibody concentrations were 8.5 U/mL and 50.4 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 66.6 U/mL and 195.3 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. And after the second dose of vaccine, the median antibody concentrations were 344.8 U/mL and 9941.0 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 620.3 U/mL and 3845.0 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. The median IFN-γ concentration was 182.8 mIU/mL in ChAdOx1-S group, which was substantially lower than the median concentration 476.8 mIU/mL in mRNA-1273 group of PD patients. Conclusion: Both vaccines were safe and resulted in comparable antibody seroconversion in PD patients when compared with volunteers. However, mRNA-1273 vaccine induced significantly higher antibody and T cell response than ChAdOx1-S in PD patients. Booster doses are recommended for PD patients after two doses of ChAdOx1-S vaccination.

Background and purpose: Early laboratory identification of group B Streptococcus (GBS, Streptococcus agalactiae) in the birth canal of pregnant women is critical for prompt administration of antimicrobial therapy and may further reduce the mortality rate due to GBS neonatal infection. Methods: A total of 164 vaginal/rectal swab specimens collected from pregnant women at 35–37 weeks of gestation were screened for GBS vaginal colonization. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS, Bruker Biotyper, Bruker Daltonik GmbH, Bremen, Germany) system was used to detect GBS from Carrot broth and LIM broth enrichment using an in-house extraction protocol. The results were compared to those by conventional broth-enriched culture/identification methods as the gold standard. BD MAX™ GBS assay (Becton Dickinson, Sparks, MD, USA) was also performed for Carrot broth-enriched specimen. Discordant results were investigated using the GeneXpert® GBS PCR assay (Cepheid Inc., Sunnyvale, CA, USA). Results: Using the extraction protocol, 33 (20.1%) of the 164 specimens were positive in Carrot broth, and 19 (11.6%) were positive in LIM broth. Using the culture protocol, 38 (23.2%) samples in Carrot broth and 35 (21.3%) in LIM broth were positive. The sensitivity, specificity, and positive and negative predictive values using the extraction protocol in Carrot broth and LIM broth compared to the gold standard conventional culture/identification method were 86.8% and 50.0%, 100% and 100%, 100% and 100%, and 96.2% and 86.9%, respectively. Conclusions: The extraction protocol with MALDI-TOF MS from Carrot broth-enriched samples provides a more rapid turnaround time, lower cost, and acceptable sensitivity and specificity to correctly identify pathogens when compared to conventional culture/identification methods.

Background: Bacteremia is a life-threatening complication of infectious diseases. Bacteremia can be predicted using machine learning (ML) models, but these models have not utilized cell population data (CPD). Methods: The derivation cohort from emergency department (ED) of China Medical University Hospital (CMUH) was used to develop the model and was prospectively validated in the same hospital. External validation was performed using cohorts from ED of Wei-Gong Memorial Hospital (WMH) and Tainan Municipal An-Nan Hospital (ANH). Adult patients who underwent complete blood count (CBC), differential count (DC), and blood culture tests were enrolled in the present study. The ML model was developed using CBC, DC, and CPD to predict bacteremia from positive blood cultures obtained within 4 h before or after the acquisition of CBC/DC blood samples. Results: This study included 20,636 patients from CMUH, 664 from WMH, and 1622 patients from ANH. Another 3143 patients were included in the prospective validation cohort of CMUH. The CatBoost model achieved an area under the receiver operating characteristic curve of 0.844 in the derivation cross-validation, 0.812 in the prospective validation, 0.844 in the WMH external validation, and 0.847 in the ANH external validation. The most valuable predictors of bacteremia in the CatBoost model were the mean conductivity of lymphocytes, nucleated red blood cell count, mean conductivity of monocytes, and neutrophil-to-lymphocyte ratio. Conclusions: ML model that incorporated CBC, DC, and CPD showed excellent performance in predicting bacteremia among adult patients with suspected bacterial infections and blood culture sampling in emergency departments.

Objectives: The aim of this study was to investigate the prognostic value of reclassified new type III monomicrobial gram-negative necrotizing fasciitis (NF) and the microbial factors associated with an increased risk of mortality. Methods: This study included 235 NF cases treated at National Taiwan University Hospital. We compared the mortality risk of NF caused by different causal microorganisms and examined the bacterial virulence genes profile and antimicrobial susceptibility pattern associated with an increase in mortality risk. Results: Type III NF (n = 68) had a mortality risk two-fold higher than type I (polymicrobial, n = 64) or type II (monomicrobial gram-positive, n = 79) NF (42.6% vs 23.4% or 19.0%, P = 0.019 and 0.002, respectively). Mortality differed by causal microorganism (Escherichia coli [61.5%], Klebsiella pneumoniae [40.0%], Aeromonas hydrophila [37.5%], Vibrio vulnificus [25.0%], polymicrobial [23.4%], group A streptococci [16.7%], and Staphylococcus aureus [16.2%], in decreasing rank, P

Background: Streptococcus gallolyticus subsp. pasteurianus (SGSP) is a commensal in the intestinal tract and a potential pathogen of neonatal sepsis. During an 11-month period, four consecutive cases of SGSP sepsis were identified in one postnatal care unit (unit A) without evidence of vertical transmission. Therefore, we initiated this study to investigate the reservoir and mode of transmission of SGSP. Method: We performed cultures of stool samples from healthcare workers in unit A and unit B (another unit without SGSP sepsis). If SGSP was positive in feces, we performed isolate pulsotyping and genotyping by using pulsed-field gel electrophoresis (PFGE) and analyzing random amplified polymorphic DNA (RAPD) patterns, respectively. Results: Five staff members in unit A showed positivity for SGSP. All samples from unit B were negative. We identified two major pulsogroups (groups C and D) by PFGE. In group D, the strains isolated from 3 consecutive sepsis patients (P1, P2 and P3) were closely related and clustered together as those from 2 staff members (C1/C2, C6). One staff (staff 4) had a direct contact history with patient (P1) confirmed to have the same clone. The last isolate of the patient in our study (P4) belonged to a distinct clone. Conclusion: We found prolonged gut colonization of SGSP in healthcare workers and its epidemiological relatedness to neonatal sepsis. Fecal-oral or contact transmission is a possible route of SGSP infection. Fecal shedding among staff may be associated with neonatal sepsis in healthcare facilities.

From January 2020 to December 2022, there was a total of 8,872,955 confirmed COVID-19 cases in Taiwan. In addition, a total of 15,253 COVID-19 related deaths were reported. During these three years, the government and health authority did many efforts to response this pandemic. In the early pandemic, Taiwan Central Epidemic Command Center was established in the early 2020 to organize associated resource, develop effective policy and implement strict intervention. In response to COVID-19 pandemic, many infection control policy and interventions, including universal mask wearing with increasing production of face mask, hand hygiene, border control, introduce of digital technology incorporating big data, quarantine of COVID-19 cases, travel and gathering restriction, were implemented. In the meanwhile, two COVID-19 vaccines, namely MVC-COV1901 and UB-612, have been developed under the support of government. Furthermore, MVC-COV1901 was taken into clinical practice after received emergency use approval. In addition, two traditional Chinese medicines, including NRICM101 and NRICM102 showed their promising effect against SARS-CoV-2 infection and were recommended as potential therapeutic options for COVID-19. During the pandemic, the nonpharmacologic intervention help reduce many infectious diseases, especially for airborne/droplet-transmitted diseases. However, COVID-19 exhibited some adverse impacts on the healthcare systems, such as emergency medical service on out of hospital cardiac arrest, cancer screening, HIV screening and prevention services, and public health, namely the psychosocial status of healthcare workers. Although the outbreak of SARS-CoV-2 infections may gradually subsided, we should keep monitoring its associated impact and appropriately response to this pandemic.

ABSTRACT Viral load quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a critical measure for monitoring clinical responses of patients with COVID-19. The cobas SARS-CoV-2 Duo (Roche Molecular Systems, Inc.) uses the cobas 6800/8800 platform and is an automated real-time reverse transcription PCR (RT-PCR) assay for the qualitative detection of SARS-CoV-2 RNA (ORF1a and ORF1a/b non-structural regions) in nasal and nasopharyngeal specimens. This assay also performs quantitation of the SARS-CoV-2 RNA level in the collected specimen. The precision, accuracy, and linearity of the cobas SARS-CoV-2 Duo test were assessed and correlated with the cycle threshold (Ct) value of the cobas SARS-CoV-2 assay, and the cobas Liat SARS-CoV-2 and influenza A/B assay (Inf A/B) (cobas Liat) in 201 clinical nasopharyngeal swab specimens. The analytical measurement range of the cobas SARS-CoV-2 Duo has been verified to be 1.0E + 02 IU/mL to 1.0E + 09 IU/mL. The between- and within-run precision evaluation and the linearity results (R 2 = 0.9961) of the cobas SARS-CoV-2 Duo were acceptable based on the verification criteria. A total of 201 nasopharyngeal specimens were evaluated. The positive, negative, and total agreements between the cobas SARS-CoV-2 Duo and the cobas SARS-CoV-2 assay were 93.5% (157 of 168), 75% (33 of 44), and 92.5% (186 of 201), respectively. The qualitative results (Ct values) from the cobas SARS-CoV-2 and the cobas Liat demonstrated good agreement with the quantitative results from the cobas SARS-CoV-2 Duo assay. In conclusion, the diagnostic performance of the cobas SARS-CoV-2 Duo assay is appropriate. It is a precise, accurate, and sensitive method for the detection of SARS-CoV-2 RNA and is comparable to two qualitative assays. IMPORTANCE Quantitative SARS-CoV-2 tests for viral load are necessary to guide patient treatment, as well as to determine infection control measures and policies. Although the real-time RT-PCR assays can report the Ct value to estimate the viral load, there are several serious concerns regarding the use of Ct values. Importantly, Ct values can vary significantly among between- and within-run methods. The diagnostic performance of the cobas SARS-CoV-2 Duo is appropriate. It is a precise, accurate, and sensitive method for the detection of SARS-CoV-2 RNA and is comparable to two qualitative assays (the cobas SARS-CoV-2 and the Liat cobas SARS-CoV-2 and Inf A/B). In contrast, using the Ct value to estimate viral load is not reliable, and utilization of a quantitative detection test, such as the cobas SARS-CoV-2 Duo, to accurately measure the viral load is needed.

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.

Multisystem inflammatory syndrome in children (MIS-C) is a dysregulated autoimmune-mediated illness in genetically susceptible patients following COVID-19 with an interval of 2–6 weeks. The median age of patients with MIS-C is 6–11 years. Most common manifestations are involvement of gastrointestinal tract, cardiovascular system, hematological system, and mucocutaneous system. Respiratory tract, neurological system, musculoskeletal system, and kidney are less frequently affected. Mucocutaneous manifestations and coronary artery abnormalities characteristic for Kawasaki disease (KD) may be observed in a significant proportion of MIS-C patients that may make the differential diagnosis be difficult for some patients, especially in the post-pandemic era. The mortality rate is 1–3%. Management and prognosis of MIS-C are similar to that of KD. MIS-C and KD may share a common pathogenic process. Based on the observation of MIS-C-like illness in uninfected neonates, i.e. multisystem inflammatory syndrome in neonates, both MIS-C and KD may be a consequence of dysregulated, over-exaggerated humoral immune responses triggered by a specific infectious agent.

ABSTRACT The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain. This retrospective study was conducted in Taiwan between 2011 and 2020. A microbiological cure was defined as the requirement for a minimum of three consecutive negative cultures following culture conversion that continued until the completion of anti-MAC treatment. A total of 97 patients with MAC-PD were enrolled in this study. The sputum smear-negative conversion rate was 40% (19/47). Thirty (31%) patients achieved sputum culture-negative conversion rates within 3 years after treatment initiation. All patients with negative sputum culture conversion rates achieved microbiological cure. Patients treated with a macrolide + rifamycin + ethambutol (M + R + EMB)-based regimen had a higher microbiological cure rate than the other patients (39% vs 17%, P = 0.023). Patients with persistently positive sputum smears after 6 months of treatment had a lower microbiological cure rate than those with negative sputum smears (6% vs 44%, P < 0.001). Among 30 patients with microbiological cure, the median time from sputum culture conversion to treatment completion was 221.5 (0–483) days, and the 1-year relapse rate was 17%. Treatment with the M + R + EMB-based regimen was associated with a higher microbiological cure rate, and patients with persistently positive sputum smears after 6 months of treatment had a lower microbiological cure rate. IMPORTANCE The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain. In this study, patients with MAC-PD treated with a macrolide + rifamycin + ethambutol (M + R + EMB)-based regimen had a higher microbiological cure rate than those treated with other regimens. After 6 months of treatment, patients with persistently positive sputum smears had a lower microbiological cure rate than those with negative sputum smears. Among patients with microbiological cure, the median time from sputum culture conversion to treatment completion was 221.5 days (range, 0–483), and the 1-year relapse rate was 17%.

Background and purpose: This study aimed to investigate the etiologies of sexually transmitted infections (STIs) among men who have sex with men (MSM) in Taiwan. Methods: Two commercial assays, the BD MAX Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC), and Trichomonas vaginalis (TV) panel and the Allplex™ STI Essential assay (CT, GC, Mycoplasma genitalium [MG], Mycoplasma hominis [MH], Ureaplasma urealyticum [UU], Ureaplasma parvum [UP], and TV) were evaluated. During the first stage, urine and rectal swab samples from 168 patients were evaluated using the BD MAX assay, and the multiplex RT-PCR Allplex™ STI Essential assay was applied only to the patients with positive results on the BD MAX asay (n = 49). During the second stage, urine and rectal swab samples from 90 patients were evaluated using the BD MAX assay and the Allplex™ qPCR. Results: The Allplex qPCR identified all CT, missed one and additionally one TV from the positive samples (n = 49) by the BD MAX assay in the first stage. At the second stage, both commercial assays showed similar detection rate of CT, NG or CT/NG coinfection (11.1%, 1.1% and 4.4% by the BD MAX assay; 10.0%, 1.1% and 2.2% by the Allplex qPCR). The positivity rates of MG, MH, and UU by the Allplex qPCR were 4.4%, 2.2%, and 12.2%, respectively, for urine samples and 10%, 13.3%, and 22.2%, respectively, for anal swab samples. Conclusions: High rates of STI-associated etiologies were observed in MSM. The positive rates were higher in rectal swabs than in urine samples.

At present, there are more than 560 million confirmed cases of the coronavirus disease 2019 (COVID-19) worldwide. Although more than 98% of patients with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection can survive acute COVID, a significant portion of survivors can develop residual health problems, which is termed as long COVID. Although severe COVID-19 is generally associated with a high risk of long COVID, patients with asymptomatic or mild disease can also show long COVID. The definition of long COVID is inconsistent and its clinical manifestations are protean. In addition to general symptoms, such as fatigue, long COVID can affect many organ systems, including the respiratory, neurological, psychosocial, cardiovascular, gastrointestinal, and metabolic systems. Moreover, patients with long COVID may experience exercise intolerance and impaired daily function and quality of life. Long COVID may be caused by SARS-CoV-2 direct injury or its associated immune/inflammatory response. Assessment of patients with long COVID requires comprehensive evaluation, including history taking, physical examination, laboratory tests, radiography, and functional tests. However, there is no known effective treatment for long COVID. Based on the limited evidence, vaccines may help to prevent the development of long COVID. As long COVID is a new clinical entity that is constantly evolving, there are still many unknowns, and further investigation is warranted to enhance our understanding of this disease.

Background: Multi-drug resistant Enterobacterales is a growing health threat. Imipenem/relebactam and meropenem/vaborbactam, are not clinically used in Taiwan and the susceptibility is lack from routine laboratory tests. Methods: Broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) breakpoints criteria. Isolates that were not susceptible to imipenem (MIC ≥ 2 mg/L), imipenem/relebactam (MIC ≥ 2 mg/L), or ceftolozane-tazobactam (MIC ≥ 4 mg/L) were selected for further molecular testing for genes encoding extended-spectrum beta-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases by multiplex PCR assays. Results: A total of 290 Enterobacterales isolates from 9 participating hospitals were collected in 2020. Escherichia coli (n = 135, 46.6%) and Klebsiella pneumoniae (n = 88, 30.3%) were two leading pathogens of all Enterobacterales isolates. The antimicrobial agents with susceptibility rates more than 90% included amikacin (99.3%, 288/290), ertapenem (90.0%, 261/290), meropenem (97.2%, 282/290), imipenem/relebactam (94.8%, 275/290) and meropenem/vaborbactam (99.3%, 288/290). K. pneumoniae isolates were less susceptible to ertapenem, imipenem, meropenem, piperacillin-tazobactam and ceftozolane/tazobactam than E. coli (all p

ABSTRACT: Objectives: This study aimed to investigate the geographic distribution of carbapenem-resistant Acinetobacter baumannii (CR-AB) isolates in the Asia-Pacific region. Methods: We collected A. baumannii isolates using the Antimicrobial Testing Leadership and Surveillance program from 2012 to 2019. The minimum inhibitory concentrations (MICs) of the isolates were determined using the broth microdilution method. The major carbapenemase genes were identified using multiplex polymerase chain reaction assays for the isolates collected between 2012 and 2014. CR-AB was defined as isolates with meropenem MICs ≥8 mg/l. Results: In total, 2674 A. baumannii isolates were collected from 13 countries, of which 1918 (71.7%) were CR-AB. The carbapenem resistance rates among A. baumannii isolates were as low as 2.8% and 6.5% in Japan and Australia, respectively, but as high as 88% and 87.2% in South Korea and India, respectively. Of the 232 CR-AB isolates that underwent carbapenemase gene screening, 224 (96.6%) harbored at least one carbapenemase gene. A total of 226 carbapenemase genes were detected, with blaOXA-23 (94.7%, 214/226) being the most dominant, followed by blaOXA-72 (2.7%, 6/226), blaOXA-58 (2.2%, 5/226), and blaNDM-1 (0.4%, 1/226). CR-AB isolates had >80% resistance to amikacin, ampicillin/sulbactam, cefepime, ceftazidime, ciprofloxacin, levofloxacin, and piperacillin/tazobactam. The rates of CR-AB resistance to minocycline and colistin were 7.2% (31/429) and 1.7% (23/1368). For cefoperazone/sulbactam and tigecycline, 50.2% (527/1049) and 93.3% (1789/1918) of CR-AB isolates had an MIC ≤16 mg/l and ≤2 mg/l, respectively. Conclusion: The prevalence of carbapenem resistance in A. baumannii showed significant differences among countries in the Asia-Pacific region, and the treatment options were limited.

Abstract An efficient host immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2, COVID‐19) appears to be crucial for controlling and resolving this viral infection. However, many studies have reported autoimmune characteristics in severe COVID‐19 patients. Moreover, clinical observations have revealed that COVID‐19‐associated acute distress respiratory syndrome shares many features in common with inflammatory myopathy including interstitial lung disease (ILD), most particularly rapidly progressive (RP)‐ILD. This study explored this phenomenon by seeking to identify and characterize myositis‐specific and related autoantibodies in 25 COVID‐19 patients with mild or severe symptoms. Line blot analysis with the EUROLINE Myopathies Ag kit identified 9 (36%) patients with COVID‐19 with one or more autoantibodies against several myositis‐related antigens (Jo‐1, Ku, Mi‐2β, PL‐7, PL‐12, PM‐Scl 75, PM‐Scl 100, Ro‐52, and SRP); no anti‐MDA5 antibodies were detected. As the presence of antibodies identified by line blots was unrelated to disease severity, we further characterized the autoantibodies by radioimmunoassay, in which [35S]methionine‐labeled K562 cellular antigens were precipitated and visualized by gel electrophoresis. This result was confirmed by an immunoprecipitation assay and immunoblotting; 2 patients exhibited anti‐Ku70 and anti‐Ku80 antibodies. Our data suggest that it is necessary to use more than one method to characterize and evaluate autoantibodies in people recovered from COVID‐19, in order to avoid misinterpreting those autoantibodies as diagnostic markers for autoimmune diseases.

Background: Patients with invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA), especially those with an elevated minimal inhibitory concentration (MIC) of vancomycin (VA), are likely to have treatment failure and poor outcomes. The aim of this study was to delineate and correlate the genotypes and phenotypes of clinical VA-intermediate S. aureus (VISA) from invasive infections in Taiwan. Methods: Between 2006 and 2010, a total of 670 non-duplicate MRSA isolates were collected from patients with invasive infections, mostly from blood, as part of a nationwide antimicrobial surveillance program named Tigecycline in vitro Surveillance in Taiwan. Among them, 10 (1.5%) VISA (VA MIC = 4 mg/L) isolates were identified. Molecular typing with staphylococcal cassette chromosome mec (SCCmec), multilocus sequence typing, staphylococcal protein A (spa), mec-associated hypervariable region (dru), accessory gene regulator (agr), and pulse-field gel electrophoresis, and phenotypic analysis including antibiotic susceptibility testing, gene encoding Panton-Valentine leukocidin (pvl), and superantigenic toxin profiles, were analyzed. Results: All but one isolate was defined as molecular health-care-associated MRSA: 6 as SCCmecIII-ST239-spa t037-agrI-dru7 (1 isolate) and dru14 (5 isolates), 2 as SCCmecII-ST5-spa t586-agrII-dru4, and one as SCCmecII-ST89-spa t3520-agrIII-dru7. One isolate was defined as SCCmecIV-ST59-spa t437-agrI-dru8, which was categorized as molecular community-associated MRSA. Five pulsotypes were identified; only one had a positive D-test and 3 were insusceptible to daptomycin (MIC ≧1 mg/L). Five isolates possessed sea-selk-selq, among them 4 belonged to SCCmecIII-ST239-spa t037-agrI. Conclusion: In this study, VISA was rarely isolated from invasive MRSA infections, and most cases harbored limited genotypes and corresponding phenotypes.

The rapid identification method, the Rapid Sepsityper protocol with a specific MBT-Sepsityper module (Bruker Daltonics), based on the MALDI Biotyper platform, accurately identified 93.5% (116/124) of microorganisms at the species level in the 124 flagged blood culture samples from patients with monomicrobial bloodstream infections. Gram-negative bacilli (95.6%, 43/45) had a higher identification rate than Gram-positive cocci (93.3%, 70/75) and yeasts (75%, 3/4). The Rapid Sepsityper protocol displayed poor identification performance for polymicrobial samples.

Background/Purpose: Although metronidazole is not recommended to treat Clostridioides difficile infection (CDI) in Western countries, it was still to be recommended for the treatment of non-severe CDI among Taiwanese adults in 2020. This controversy in the clinical role of metronidazole therapy for CDI was examined in a prospective clinical study. Methods: The study was conducted from January 2015 to December 2016 in three hospitals in Taiwan. Metronidazole treatment failure (MTF) was defined as the persistence of diarrhea after six days of treatment, medication modification (shifting to oral vancomycin), or death after five days of therapy. Results: Overall, 325 patients receiving metronidazole for CDI were included. The overall MTF rate was 48.6% (158 patients). Leukocyte counts of >15,000 cells/mL in peripheral blood (odd ratio [OR] 1.81; P = 0.04) and congestive heart failure (OR 3.26; P = 0.02) were independently associated with MTF. The MTF rate for patients with leukocyte counts of ≤15,000 cells/mL and no congestive heart failure, leukocyte counts of >15,000 cells/mL and no congestive heart failure, leukocyte counts of ≤15,000 cells/mL and congestive heart failure, and leukocyte counts of >15,000 cells/mL and congestive heart failure were 44.2%, 51.8%, 73.3%, and 66.7%, respectively. Of note, patients who experienced MTF had a higher recurrence rate of CDI than those with metronidazole treatment success (13.9% vs. 6.0%, P = 0.02). Conclusion: For Taiwanese adults with CDI, the failure rate of metronidazole therapy approached 50%, which suggests the reappraisal of the therapeutic role of metronidazole therapy, especially for patients with leukocytosis or underlying congestive heart failure.

Background/purpose: This study aimed to investigate the in vitro susceptibilities of carbapenem-non-susceptible Pseudomonas aeruginosa (CNSPA) and Acinetobacter baumannii (CNSAB) isolates to cefiderocol, novel β-lactamase inhibitor (BLI) combinations, new tetracycline analogues, and other comparative antibiotics. Methods: In total, 405 non-duplicate bacteremic CNSPA (n = 150) and CNSAB (n = 255) isolates were collected from 16 hospitals in Taiwan between 2018 and 2020. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibilities were interpreted according to the relevant guidelines or in accordance with results of previous studies and non-species-related pharmacokinetic/pharmacodynamic data. Results: Among the isolates tested, cefiderocol demonstrated potent in vitro activity against CNSPA (MIC50/90, 0.25/1 mg/L; 100% of isolates were inhibited at ≤4 mg/L) and CNSAB (MIC50/90, 0.5/2 mg/L; 94.9% of isolates were inhibited at ≤4 mg/L) isolates. More than 80% of CNSPA isolates were susceptible to cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and amikacin, based on breakpoints established by the Clinical and Laboratory Standards Institute. Activities of new BLI combinations varied significantly. Tetracycline analogues, including tigecycline (MIC50/90, 1/2 mg/L; 92.5% of CNSAB isolates were inhibited at ≤2 mg/L) and eravacycline (MIC50/90, 0.5/1 mg/L; 99.6% of CNSAB isolates were inhibited at ≤2 mg/L) exhibited more potent in vitro activity against CNSAB than omadacycline (MIC50/90, 4/8 mg/L). Conclusions: The spread of CNSPA and CNSAB poses a major challenge to global health. Significant resistance be developed even before a novel agent becomes commercially available. The development of on-site antimicrobial susceptibility tests for these novel agents is of great clinical importance.

Background/purpose: Streptococcus pneumoniae is an important human pathogen that causes invasive infections in adults and children. Accurate serotyping is important to study its epidemiological distribution and to assess vaccine efficacy. Methods: Invasive S. pneumoniae isolates (n = 300) from 27 teaching hospitals in China were studied. The Quellung reaction was used as the gold standard to identify the S. pneumoniae serotypes. Subsequently, multiplex PCR and cpsB gene-based sequetyping methods were used to identify the serotypes. Results: Based on the Quellung reaction, 299 S. pneumoniae isolates were accurately identified to the serotype level and 40 different serotypes were detected. Only one strain was non-typeable, and five most common serotypes were identified: 23F (43, 14.3%), 19A (41, 13.7%), 19F (41, 13.7%), 3 (31, 10.3%), and 14 (27, 9.0%). Overall, the multiplex PCR method identified 73.3 and 20.7% of the isolates to the serotype and cluster levels, respectively, with 1.7% of the isolates misidentified. In contrast, the cpsB sequetyping method identified 59.0 and 30.3% of the isolates to the serotype and cluster levels, respectively, and 7% were misidentified. Conclusions: The cpsB gene sequetyping method combined with multiplex PCR, can greatly improve the accuracy and efficiency of serotyping, besides reducing the associated costs.

The emergence of the monkeypox outbreak in early 2022 has posed a new global health threat. As of July 8, 2022, 9069 laboratory-confirmed cases have been reported, and most of them are from non-endemic countries. The monkeypox virus is an enveloped double-stranded DNA virus, and preliminary genetic data suggest that the 2022 monkeypox virus belongs to the West African clade. In the current outbreak, human-to-human transmission has been the primary transmission mode. Although direct skin-to-skin contact with lesions during sexual activities can spread the virus, it remains unclear whether monkeypox can spread through sexual contact, specifically through contaminated body fluids. The typical presentation of monkeypox includes prodromal symptoms, followed by a rash that usually begins within 1–3 days of symptom onset, and the skin lesions can last for 2–4 weeks and then gradually resolve. However, the monkeypox outbreak in 2022 may exhibit atypical features. A definite diagnosis of monkeypox virus infection requires nucleic acid amplification testing via the polymerase chain reaction method. Supportive care is essential, and antiviral therapy is not considered for all affected patients, but recommended for those at highrisk for severe diseases. The mitigation of monkeypox outbreaks include enhanced case detection, case isolation, contact tracing, and post-exposure vaccination. In conclusion, the current monkeypox outbreak is a new threat during the COVID-19 pandemic. Clinicians should be aware of this new situation, which presents a different scenario from those of prior outbreaks. Global health systems should develop effective strategies to mitigate the spread of monkeypox.

Monkeypox virus (MPXV), genetic closely linked to the notorious variola (smallpox) virus, currently causes several clusters and outbreaks in the areas outside Africa and is noted to be phylogenetically related to the West African clade. To prepare for the upsurge of the cases of monkeypox in the Europe and North America, two vaccines, Jynneos® in the U.S. (Imvamune® in Canada or Imvanex® in the Europe) and ACAM2000® (Acambis, Inc.) initially developed in the smallpox eradication program, can provide protective immunity to monkeypox, and their production and availability are rapidly scaled up in the response to the emerging threat. So far, these two vaccines are recommended for people at a high risk for monkeypox, instead of universal vaccination. Tecovirimat, an inhibitor of extracellular virus formation, and brincidofovir, a lipid conjugate of cidofovir, both are in vitro and in vivo active against MPXV, and are suggested for immunocompromised persons, who are at risk to develop severe diseases. However, current general consensus in the response to the monkeypox outbreak among public health systems is early identification and isolation of infected patients to prevent its spread.

ABSTRACT: Objectives: To investigate the clinical outcomes and risk factors of mortality in patients with rheumatic diseases complicated by Pneumocystis pneumonia (PCP). Methods: Between November 2015 and April 2021, patients with rheumatic diseases with PCP in a tertiary referral hospital were retrospectively enrolled. The diagnosis of PCP requires the fulfillment of clinical, radiographic, and microbiological criteria. Factors associated with in-hospital, 30-day, and 90-day mortality were evaluated. Results: A total of 128 patients with rheumatic diseases who had a positive quantitative polymerase chain reaction assay for Pneumocystis jirovecii were screened, and 72 patients were included in the final analysis. The median (interquartile range [IQR]) pneumonia severity index (PSI) was 101.5 (77.0-132.0). The median (IQR) adjunctive corticosteroid dosage was 0.6 (0.4-0.9) mg/kg/day prednisolone equivalent. The receiver operating characteristic curve analysis showed that the optimal cutoff point of median adjunctive corticosteroid dosage was 0.6 mg/kg/day to predict in-hospital, 30-day, and 90-day mortality. In the multivariable logistic regression analysis, median adjunctive corticosteroid dosage ≥0.6 mg/kg/day and PSI >90 were independent factors of in-hospital, 30-day, and 90-day mortality. Conclusion: A median adjunctive corticosteroid dosage of ≥0.6 mg/kg/day might be associated with mortality in patients with rheumatic diseases complicated by PCP.

The Coronavirus Disease 2019 (COVID-19) pandemic continues to infect people worldwide. While the vaccinated population has been increasing, the rising breakthrough infection persists in the vaccinated population. For living with the virus, the dietary guidelines to prevent virus infection are worthy of and timely to develop further. Tannic acid has been demonstrated to be an effective inhibitor of coronavirus and is under clinical trial. Here we found that two other members of the tannins family, oligomeric proanthocyanidins (OPCs) and punicalagin, are also potent inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with different mechanisms. OPCs and punicalagin showed inhibitory activity against omicron variants of SARS-CoV-2 infection. The water extractant of the grape seed was rich in OPCs and also exhibited the strongest inhibitory activities for viral entry of wild-type and other variants in vitro. Moreover, we evaluated the inhibitory activity of grape seed extractants (GSE) supplementation against SARS-CoV-2 viral entry in vivo and observed that serum samples from the healthy human subjects had suppressive activity against different variants of SARS-CoV-2 Vpp infection after taking GSE capsules. Our results suggest that natural tannins acted as potent inhibitors against SARS-CoV-2 infection, and GSE supplementation could serve as healthy food for infection prevention.

Abstract Lung cancer remains a major health problem despite the considerable research into prevention and treatment methods. Through a deeper understanding of tumors, patient‐specific ex vivo spheroid models with high specificity can be used to accurately investigate the cause, metastasis, and treatment strategies for lung cancer. Biofabricate lung tumors are presented, consisting of patient‐derived tumor spheroids, endothelial cells, and lung decellularized extracellular matrix, which maintain a radial oxygen gradient, as well as biophysicochemical behaviors of the native tumors for precision medicine. It is also demonstrated that the developed lung‐cancer spheroid model reproduces patient responses to chemotherapeutics and targeted therapy in a co‐clinical trial, with 85% accuracy, 86.7% sensitivity, and 80% specificity. RNA sequencing analysis validates that the gene expression in the spheroids replicates that in the patient's primary tumor. This model can be used as an ex vivo predictive model for personalized cancer therapy and to improve the quality of clinical care.

This paper provides a comprehensive summary of evidence to explore and position the role of serology testing in the context of coronavirus disease 19 (COVID-19) immunization and policy response in the Asia-Pacific (APAC) region. The document builds on a review of academic literature and existing policies followed by a process of discussion, validation, and feedback by a group of six experts. Six countries and territories—Australia, Hong Kong, India, Indonesia, Thailand, and Taiwan—were sampled to highlight the differing contexts and scenarios in the region. The review includes an overview of (1) the impact of the COVID-19 pandemic, including the emergence of Variants of Concern (VOCs), especially Omicron, (2) the introduction of immunization, (3) the available testing options and potential use of serology testing, (4) the landscape of guidelines and recommendations for their use, and (5) the barriers and challenges to implementing serology testing as a tool to support COVID-19 immunization. Based on the findings, the co-authors propose a set of recommendations to resolve knowledge gaps, to include the use of serology testing as part of the policy response, and to ensure adequate means of implementation. This paper’s target audience includes members of the academic community, medical societies, health providers and practitioners, and decision-makers.

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.

Background/Purpose: There are limited studies on species distribution and susceptibility profiles of Aspergillus strains isolated from patients with otomycosis in China. Methods: A total of 69 confirmed Aspergillus species isolates were obtained from ear swabs of patients diagnosed with otomycosis from 2017 to 2018 in northern China. Identification of these Aspergillus isolates at the species level was performed using conventional morphological methods and MALDI-TOF MS in combination with molecular sequencing, and in vitro susceptibility to nine antifungal agents was evaluated using the Sensititre YeastOne system. Results: The Aspergillus section Nigri had the greatest distribution of Aspergillus isolates. A. welwitschiae (n = 25) was the most predominant isolate in section Nigri, followed by A. tubingensis (n = 12) and A. niger (n = 11). Other Aspergillus species were also isolated, including A. terreus (n = 11), A. flavus/A. oryzae (n = 8), and A. fumigatus (n = 2). Amphotericin B, posaconazole, and echinocandins were highly in vitro active against all the isolates tested. 2.9% (2/69) of the isolates were resistant to azoles in our study, including one A. niger isolate with a high MIC value for itraconazole (ITR) (16 mg/L) and one A. tubingensis isolate cross-resistant to both voriconazole (VOR) (MIC >8 mg/L) and ITR (MIC >16 mg/L). One A. welwitschiae and one A. niger isolate both had increased MIC values of 4 mg/L against VOR. Conclusions: A. welwitschiae was the most prevalent Aspergillus species isolated from patients with otomycosis. Our findings also indicated that the azole-resistant Aspergillus section Nigri should be utilized to guide clinical medication for Otomycosis.

Objectives: This study aimed to provide detailed genetic characterization of Tn6636, a multidrug-resistant and composite mobile element, in clinical isolates of Staphylococcus aureus. Methods: A total of 112 ermB-positive methicillin-susceptible S. aureus (MSSA) and 224 ermB-positive methicillin-resistant S. aureus (MRSA) isolates collected from 2000 to 2015 were tested for the presence of Tn6636. Detection of the plasmids harboring Tn6636 was performed by S1 nuclease digestion pulsed-field gel electrophoresis (PFGE) analysis, conjugation test, and whole genome sequencing (WGS). Results: Prevalence of Tn6636 in MSSA is higher than that in MRSA. Ten MSSA isolates and 10 MRSA isolates carried Tn6636. The 10 MSSA isolates belonged to three sequence types (ST), including ST7 (n = 6), ST5 (n = 3), and ST59 (n = 1). The 10 MRSA isolates belonged to ST188 (n = 8) and ST965 (n = 2). Analysis of plasmid sequences revealed that Tn6636 was harbored by six different mosaic plasmids. In addition to resistance genes, some plasmids also harbored toxin genes. Conclusion: The presence of multi-resistant Tn6636 in plasmids of both MSSA and MRSA with various STs suggests its broad dissemination. Results indicate that Tn6636 has existed for at least 16 years in Taiwan. The mosaic plasmids harboring Tn6636 can be transferred by conjugation. Ongoing surveillance of Tn6636 is essential to avoid continued spreading of resistant plasmids.

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

ABSTRACT: Objectives: Cefiderocol (CFDC), a siderophore cephalosporin, is active against Gram-negative bacteria including carbapenem-resistant Acinetobacter baumannii (CRAB). In this study, 100 CRAB isolates from patients with bacteraemia in Taiwan were characterised, among which 21 CFDC-non-susceptible isolates were identified with a minimum inhibitory concentration (MIC) of ≥8 mg/L. Methods: The effect of avibactam on CFDC activity was evaluated using broth microdilution methods according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Whole-genome sequencing (WGS) was performed on all CFDC-non-susceptible isolates (MIC ≥ 8 mg/L) for multilocus sequence typing (MLST) analysis, possession of β-lactamase genes and identification of possible variations in the PiuA iron transporter. Results: Addition of avibactam, a diazabicyclooctane inhibitor for serine-type β-lactamases, resulted in a ≥8-fold decrease in the CFDC MIC for 15 of 21 CFDC-non-susceptible isolates compared with only 1 of 79 CFDC-susceptible isolates (MIC ≤ 4 mg/L). WGS analysis confirmed that all CFDC-non-susceptible isolates harboured multiple β-lactamases including ADC-30 homologues, OXA-23 and OXA-66. One isolate with a high MIC (>32 mg/L) had a PER-type extended-spectrum β-lactamase (ESBL) gene. Twenty other isolates belonged to ST455, ST473 and ST787. Among these, thirteen ST455 isolates were deficient in PiuA, a siderophore uptake receptor that may be required for optimal penetration of CFDC. Conclusion: MICs of CFDC-non-susceptible CRAB isolates from Taiwan could be significantly decreased to susceptible levels by the addition of avibactam, suggesting the involvement of β-lactamases in resistance. Among the 21 CFDC-non-susceptible isolates, 1 isolate had a PER-type ESBL gene and 13 isolates lacked a PiuA iron siderophore transporter.

Objectives. Acute respiratory distress syndrome (ARDS) is a critical complication in severe COVID-19 patients. The intravenous infusion (IVF) of umbilical cord- (UC-) mesenchymal stem cells (MSCs), validated to substantially reduce the release of several inflammatory cytokines in vivo, was also shown to exhibit benefits in improving hypoxemia among severe COVID-19 patients. A single dose of IVF-UC-MSCs therapy for severe COVID-19 patients was shown to alleviate the initial ARDS severity, but have 50%–67% case-fatality rates. In Taiwan, few adult patients with severe COVID-19-induced ARDS receiving compassionate adjuvant treatment consisting of either a single dose (1–10 × 106 cells/kg body weight (kg BW)) or three doses (5 × 106 cells/kg BW in each dose) of IVF-UC-MSCs had good outcomes. However, the optimal dosage and rounds of IVF-UC-MSCs administration for the treatment of severe COVID-19 patients with ARDS are undetermined. Methods. We reviewed the 2020–2022 PubMed literature database concerning the clinical efficacy of IVF-UC-MSCs among severe COVID-19 patients. Results. The data of COVID-19 case series in the PubMed literature revealed a notable heterogeneity in the therapeutic dosage (a single dose: 1–10 × 106 cells/kg BW; and three doses: 50–200 × 106 cells/kg BW in each dose) and the post-ARDS days of IVF-UC-MSCs administration (a single dose: 1–12; and multiple doses: 5–14) for the treatment of severe COVID-19-associated ARDS. The survival rates among these severe COVID-19 patients ranged from 50% to 76%. However, an overall rate of 93.1% of significant improvement in hypoxemia was observed for the COVID-19 survivors receiving IVF-UC-MSCs at the initial ARDS stage. Conclusions. According to our analysis, the ideal treatment dosage of IVF-UC-MSCs for severe COVID-19-induced ARDS is likely 5 × 106 cells/kg BW for three cycles within 5 days of ARDS onset in severe COVID-19 patients.

Background: Among the individuals with hematological malignancy (HM) complicated with Clostridioides difficile infection (CDI), the variables associated with in-hospital mortality and recurrence of CDI were investigated. Material and methods: Including adults with HM and those without malignancy suffering from CDI from January 2015 to December 2016 in three hospitals in Taiwan. Results: Totally 314 patients including 77 with HM and 237 patients without malignancy were included. HM patients more often had low leukocyte counts (

Background/purpose: Although Streptococcus gallolyticus subspecies pasteurianus (SGSP) is a rare pathogen in children, it can cause invasive infections among neonates and infants. Herein, we report bacteremia/meningitis caused by SGSP in three neonates and review the literature on bacteremia and/or meningitis caused by this organism. Methods: Three neonates, referred from an obstetrics clinic within a 2-month period, presented with invasive SGSP infections. The bacterial isolates were analyzed using Bruker Biotyper MALDI-TOF, sequencing of 16S rRNA and sodA genes (encoding manganese dependent superoxide dismutase), and PCR restriction fragment length polymorphism assay of groESL gene. Molecular typing was performed to evaluate the genetic relatedness. Results: The median onset age of infection in the three neonates was 3 days (range 2–5 days). They were delivered through cesarean section in the same operation room under different doctors, and were cared for by different nurses. Patient A presented with bacteremia, patient B with bacteremia and meningitis, and patient C with meningitis. Four isolates were identified as SGSP and were susceptible to penicillin G, cefotaxime, and vancomycin. All patients were treated with ampicillin plus cefotaxime for 14 days, and no complications were observed. The molecular typing results suggested that all isolates belonged to a single clone, which indicated the possibility of an outbreak in the obstetrics clinic. Conclusion: Infection by a rare pathogen such as SGSP in multiple patients belonging to a single healthcare unit indicates that detailed investigation and stringent infection control policy are necessary for preventing further outbreaks of such diseases.

Background/purpose: This study aimed to investigate the clinical characteristics and outcomes of bacteremia caused by Haemophilus and Aggregatibacter species in patients who were treated at a medical center between 2006 and 2018. Methods: Haemophilus and Aggregatibacter isolates were identified up to the species level using Bruker Biotyper MALDI-TOF analysis and ancillary 16S rRNA gene sequencing analysis (in case of ambiguity). Clinical characteristics and outcomes of patients with bacteremia caused by these organisms were evaluated. Results: Sixty-five Haemophilus and Aggregatibacter species isolates causing bacteremia were identified from nonduplicated patients, including 51 (78.5%) Haemophilus influenzae, 6 (9.2%) Haemophilus parainfluenzae, 1 (1.5%) Haemophilus haemolyticus, 3 (4.6%) A. aphrophilus, and 4 (6.2%) A. segnis. Hospital mortality was observed in 18 (28.1%) of 64 patients with bacteremia caused by Haemophilus (n = 57) and Aggregatibacter species (n = 7). The majority of patients with bacteremia had community-acquired disease with low severity. The average Sequential Organ Failure Assessment (SOFA) score was low (4.4 ± 4.7). But, a higher SOFA score (adjusted odds ratio 2.5, 95% confidence interval 1.22–5.12; P = 0.01) was an independent factor predicting poor 7-day clinical outcomes in patients with community-acquired H. influenzae bacteremia (n = 39). Conclusions: The overall hospital mortality of 28.1% was observed among patients with bacteremia due to Haemophilus and Aggregatibacter species. A higher SOFA score was and independent predictor of poor 7-day clinical outcomes in patients with community-acquired H. influenzae bacteremia.