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Resveratrol, a naturally occurring dietary compound with chemopreventive properties has been reported to trigger a variety of cancer cell types to apoptosis. Whether resveratrol shows any activity on human nasopharyngeal carcinoma (NPC) cells remained to be determined. The aim of this study was to investigate the effect and mechanism of resveratrol on human NPC cells. Treatment of resveratrol resulted in significant decrease in cell viability of NPC cell lines in a dose- and time-dependent manner. A dose-dependent apoptotic cell death was also measured by flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled resveratrol treatment resulted in a significant loss of mitochondrial transmembrane potential, release of cytochrome c, enhanced expression of Fas ligand (FasL), and suppression of glucose-regulated protein 78 kDa (GRP78). These were followed by activation of caspases-9, -8, -4, and -3, subsequently leading to DNA fragmentation and cell apoptosis. Furthermore, up-regulation of proapoptotic Bax and down-regulation of antiapoptotic Bcl-2 protein were also observed. Taken together, resveratrol induces apoptosis in human NPC cells through regulation of multiple apoptotic pathways, including death receptor, mitochondria, and endoplasmic reticulum (ER) stress. Resveratrol can be developed as an effective compound for human NPC treatment. J. Cell. Physiol. 226: 720-728, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose: The presence of anti-interferon-γ autoantibodies (AutoAbs-IFN-γ) is not rare in patients suffering from persistent non-tuberculous mycobacterial (NTM) infections that are characteristic of adult-onset immunodeficiency syndrome. The immune disturbances in this distinct disorder remain to be elucidated. Methods: Patients with NTM infections but without effective response over 3 months' treatment were referred to our institute to quantify their level of AutoAbs-IFN-γ after excluding defective IL12/23-IFN-γ circuit and reactive oxygen species production. The AutoAbs-IFN-γ and percentage of lymphocyte subpopulations most relevant to T and B cell pools were assessed and compared with age-matched healthy controls. Results: A total of 31 patients were enrolled during the 15-year study period (2008–2022), 20 patients with > 50% suppression of IFN-γ detection at 1:100 serum dilution were classified into the Auto-NTM group. The remaining 11 with negligible suppression were assigned to the No Auto-NTM group. Mycobacterium chimaera-intracellulare group (MAC), M. kansasii, and M. abscessus were the most common pathogens. Pneumonia (19 vs 7), lymphadenitis (11 vs 5), Salmonella sepsis (6 vs 2), osteomyelitis (5 vs 1), and cutaneous herpes zoster (4 vs 4) were the main manifestations in both the Auto-NTM and No Auto-NTM groups who had similar onset-age (55.3 vs 53.6 years; p = 0.73) and follow-up duration (71.9 vs 54.6 months; p = 0.45). The Auto-NTM group had significantly higher transitional (IgM + + CD38 + +), CD19 + CD21-low, and plasmablast (IgM-CD38 + +) in the B cell pool, with higher effector memory (CD4 + /CD8 + CD45RO + CCR7 −), senescent CD8 + CD57 + , and Th17 cells, but lower naïve (CD4 + /CD8 + CD45RO − CCR7 +) and Treg cells in the T cell pool when compared to the No Auto-NTM and healthy groups. NTM patients with/without AutoAbs-IFN-γ had lower Th1-like Tfh (CD4 + CXCR5 + CXCR3 + CCR6 −) cells. All Auto-NTM patients still had non-remitted mycobacterial infections and higher AutoAbs-IFN-γ despite anti-CD20 therapy in 3 patients. Conclusion: In patients with suspected adult-onset immunodeficiency syndrome, two thirds (20/31) were recognized as having significantly inhibitory AutoAbs-IFN-γ with higher antibody-enhancing transitional, CD19 + CD21-low and plasmablast B cells; as well as higher effector memory, senescent CD8 + CD57 + and Th17 cells, but lower naïve T and Treg cells in contrast to those with negligible AutoAbs-IFN-γ. Such immunophenotyping disturbances might correlate with the presence of AutoAbs-IFN-γ. However, the mutual mechanisms need to be further clarified. [ABSTRACT FROM AUTHOR]

l COVID-19 vaccines impact interferon-γ release assay readouts l COVID-19 vaccines significantly change the Nil and Mitogen-Nil values l COVID-19 vaccines did not change interferon-γ release assay interpretation in most cases Interferon-γ release assays (IGRAs) are widely used in public health practice to diagnose latent tuberculosis. During the COVID-19 pandemic and rollout of COVID-19 vaccination, it has remained unclear whether COVID-19 vaccines interfere with IGRA readouts. We prospectively recruited healthcare workers during their annual occupational health examinations in 2021. Baseline IGRA readouts were compared with follow-up data after the participants had received two doses of COVID-19 vaccination. A total of 134 baseline IGRA-negative cases (92 with ChAdOx1 vaccine, 27 with mRNA-1273 vaccine, and 15 with heterologous vaccination) and seven baseline IGRA-positive cases were analyzed. Among the baseline IGRA-negative cases, there were decreased interferon-γ concentrations over the Nil (P = 0.005) and increased Mitogen-Nil (P < 0.001) values after vaccination. For TB2-Nil value, a similar trend (P = 0.057) of increase was observed. Compared with the 0.35 IU/ml threshold, the baseline and follow-up readout differences were less than |± 0.10| IU/ml over the TB1-Nil and TB2-Nil values in >90% baseline IGRA-negative cases. No significant readout difference was observed among baseline IGRA-positive cases. COVID-19 vaccination did not change IGRA interpretation in most cases. Cases showing conversion/borderline IGRA readouts should be given special consideration. [ABSTRACT FROM AUTHOR]

• For HIV genotyping, the undetected minority populations by standard Sanger sequencing (SS) were not always minor. • 9–15% of cases with treatment failure/interruption had underestimated drug resistant variants accounting for ≥15–25% total viral population. • The study suggested that 10-15% threshold deep sequencing may be considered a suitable substitute for SS on HIV drug resistant mutation detection. The clinical utilisation of deep sequencing in HIV treatment has been hindered due to its unknown correlation with standard Sanger genotyping and the undetermined value of minority drug resistance mutation (DRM) detection. To compare deep sequencing performance to standard Sanger genotyping with clinical samples, in an effort to delineate the correlation between the results from the two methods and to find the optimal deep sequencing threshold for clinical utilisation. We conducted a retrospective study using stored plasma collected from August 2014 to March 2018 for HIV genotyping with the commercial Sanger genotyping kit. Samples with available Sanger genotyping reports were further deep sequenced. Drug resistance was interpreted according to the Stanford HIV drug resistance database algorithm. At 15–25% minority detection thresholds, 9–15% cases had underestimated DRMs by Sanger sequencing. The concordance between the Sanger and deep sequencing reports was 68–82% in protease-reverse transcriptase region and 88–97% in integrase region at 5–25% thresholds. The undetected drug resistant minority variants by Sanger sequencing contributed to the lower negative predictive value of Sanger genotyping in cases harbouring DRMs. Use of deep sequencing improved detection of antiretroviral resistance mutations especially in cases with virological failure or previous treatment interruption. Deep sequencing with 10–15% detection thresholds may be considered a suitable substitute for Sanger sequencing on antiretroviral DRM detection. [ABSTRACT FROM AUTHOR]

• Multicentre surveillance of antimicrobial susceptibility among clinically important Gram-negative bacteria (GNB) in Taiwan. • Increasing carbapenem resistance among clinically important GNB, especially among nosocomial isolates. • bla KPC , especially the bla KPC-2 variant, was detected in 48.4% of carbapenem-resistant Klebsiella pneumoniae isolates. • Low prevalence of the mcr-1 gene. • mcr-1 was detected in different Enterobacteriaceae species, raising concern of potential dissemination. Multicentre surveillance of antimicrobial susceptibility of clinically important Gram-negative bacteria (GNB) from 16 Taiwanese hospitals was performed. Escherichia coli (n = 398), Klebsiella pneumoniae (n = 346), Pseudomonas aeruginosa (n = 252) and Acinetobacter baumannii complex (ABC) (n = 188) bloodstream isolates, non-typhoidal Salmonella (n = 230) and Shigella flexneri (n = 18) from various sources were collected. Antimicrobial MICs were determined using broth microdilution. Genes encoding K. pneumoniae carbapenemases (KPCs), New Delhi metallo-β-lactamases (NDMs), Verona integron-encoded metallo-β-lactamase (VIM), OXA-48-like carbapenemase (OXA-48) as well as mcr-1–5 genes were detected by molecular methods. Rates of carbapenem non-susceptibility were 2.8%, 9.0%, 0.4%, 0%, 10.3% and 48.8% for E. coli, K. pneumoniae, Salmonella, Shigella, P. aeruginosa and ABC, respectively. For carbapenemases, one (0.3%) E. coli harboured bla NDM-1. Fifteen (4.3%), two (0.6%) and two (0.6%) K. pneumoniae contained bla KPC , bla OXA-48 and bla VIM , respectively. Two (0.5%) E. coli and fourteen (4.0%) K. pneumoniae were non-wild-type according to the colistin MIC. Among Enterobacteriaceae with a colistin MIC ≥ 2 mg/L, mcr-1 was detected in one E. coli , two K. pneumoniae and three Salmonella spp. All three mcr-1 -positive Salmonella isolates were collected from community-acquired infections; none of the six mcr-1 -positive Enterobacteriaceae were carbapenem-resistant. Carbapenem resistance has increased among clinically important GNB, especially among hospital-acquired infections. bla KPC , especially the bla KPC-2 variant, was detected in approximately one-half of the carbapenem-resistant K. pneumoniae isolates in this study. Although resistance rates to colistin remained low among Enterobacteriaceae, the finding of mcr-1 from different species raises concern of potential dissemination. [ABSTRACT FROM AUTHOR]

Background: Infections caused by Klebsiella pneumoniae are common and result in high mortality rates. In vitro studies demonstrated the potency of cefoperazone/sulbactam (CPZ/SUL) against Klebsiella pneumoniae. However, the clinical efficacy of CPZ/SUL for the treatment of K. pneumoniae bacteremia has not been studied., Objectives: This study aimed to associate the clinical outcomes of patients with bacteremia with the minimal inhibitory concentrations (MICs) of CPZ/SUL against the causative K. pneumoniae isolates., Methods: This multicenter, retrospective study was conducted in Taiwan between July 2017 and April 2021. Patients with K. pneumoniae bacteremia treated with CPZ/SUL were enrolled in this study. CPZ/SUL MICs were determined using the agar dilution method. Data on the patients' clinical outcomes and characteristics were collected and analyzed., Results: In total, 201 patients were enrolled. Among the causative K. pneumoniae isolates, 180 (89.5%) were susceptible to CPZ/SUL. Most patients (n = 156, 77.6%) had favorable outcomes. The 30-day mortality rate was 11.9% (n = 24). Multivariate risk analyses showed that higher APACHE II score (Odds Ratio [OR], 1.14; Confidence Interval [CI], 1.07-1.21; p < 0.001), metastatic tumors (OR, 5.76; CI, 2.31-14.40; p < 0.001), and causative K. pneumoniae CPZ/SUL MICs > 16 µg/ml (OR, 4.30; CI, 1.50-12.27; p = 0.006) were independently associated with unfavorable outcomes., Conclusion: Patients with K. pneumoniae bacteremia treated with CPZ/SUL at a ratio 1:1 had favorable outcomes when the CPZ/SUL MICs were ≤ 16 µg/ml. Patients with higher APACHE II scores and metastatic tumors had unfavorable outcomes., (© 2024. The Author(s).)

We conducted a comprehensive metabolomic analysis of plasma samples obtained from pregnant women who displayed varying post-vaccination antibody titers after receiving mRNA-1273-SARS-CoV-2 vaccines. The study involved 62 pregnant women, all of whom had been vaccinated after reaching 24 weeks of gestation. To quantify post-vaccination plasma antibody titers, we employed binding antibody units (BAU) in accordance with the World Health Organization International Standard. Subsequently, we classified the study participants into three distinct BAU/mL categories: those with high titers (above 2000), medium titers (ranging from 1000 to 2000), and low titers (below 1000). Plasma metabolomic profiling was conducted using 1 H nuclear magnetic resonance spectroscopy, and the obtained data were correlated with the categorized antibody titers. Notably, in pregnant women exhibiting elevated anti-SARS-CoV-2 antibody titers, reduced plasma concentrations of acetate and urea were observed. A significant negative correlation between these compounds and antibody titers was also evident. An analysis of metabolomics pathways revealed significant inverse associations between antibody titers and four distinct amino acid metabolic pathways: (1) biosynthesis of phenylalanine, tyrosine, and tryptophan; (2) biosynthesis of valine, leucine, and isoleucine; (3) phenylalanine metabolism; and (4) degradation of valine, leucine, and isoleucine. Additionally, an association between the synthesis and degradation pathways of ketone bodies was evident. In conclusion, we identified different metabolic pathways that underlie the diverse humoral responses triggered by COVID-19 mRNA vaccines during pregnancy. Our data hold significant implications for refining COVID-19 vaccination approaches in expectant mothers. KEY MESSAGES : Anti-SARS-CoV-2 antibody titers decline as the number of days since COVID-19 vaccination increases. Anti-SARS-CoV-2 antibody titers are inversely associated with acetate, a microbial-derived metabolite, and urea. Amino acid metabolism is significantly associated with SARS-CoV-2 antibody titers., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota dysbiosis in patients with NTM-LD. Reduced abundance of Prevotella copri was significantly associated with NTM-LD and its disease severity. Compromised TLR2 activation activity in feces and plasma in the NTM-LD patients was highlighted. In the antibiotics-treated mice as a study model, gut microbiota dysbiosis with reduction of TLR2 activation activity in feces, sera, and lung tissue occurred. Transcriptomic analysis demonstrated immunocompromised in lung which were closely associated with increased NTM-LD susceptibility. Oral administration of P. copri or its capsular polysaccharides enhanced TLR2 signaling, restored immune response, and ameliorated NTM-LD susceptibility. Our data highlighted the association of gut microbiota dysbiosis, systematically compromised immunity and NTM-LD development. TLR2 activation by P. copri or its capsular polysaccharides might help prevent NTM-LD.

Hepatitis C virus (HCV) infection causes many cancers, including intrahepatic cholangiocarcinoma. Whether it increases the risk of extrahepatic cholangiocarcinoma (ECC) is unknown. A 10-year nationwide population-based cohort study of the Taiwan National Health Insurance Research Database (TNHIRD) was conducted. ECC was defined by ICD-9-CM code 156 or ICD-O-3 code C23-24. Risk factors and HCV core protein expression were surveyed in patients with ECC from a tertiary-care center. Out of 11,892,067 patients, three propensity score-matched TNHIRD cohorts were matched at a 1:4:4 ratio: HCV-treated (8,331 patients with interferon-based therapy >6 months), HCV-untreated (n=33,324), and HCV-uninfected cohorts (n=33,324). The cumulative incidence of ECC [HCV-treated: 0.088%, 95% confidence interval (CI): 0.035-0.198%; HCV-untreated: 0.095%, 0.047-0.179%; HCV-uninfected: 0.048%, 0.017-0.119%] was lowest in the HCV-uninfected cohort ( P =0.0285) but was not different between the treated and untreated cohorts ( P =0.5436). HCV infection [HCV-treated cohort: hazard ratio (HR): 3.618, 95% CI HR: 1.253-10.451; HCV-untreated cohort: 2.593, 95% CI HR: 1.077-6.241; reference: HCV-uninfected cohort] and age ≥49 years (HR: 5.139, 95% CI HR: 1.613-16.369) were associated with ECC development. Among the 855 hospitalized ECC patients (males: 57%; baseline age: 63.09±11.75 years, 2008-2018), the HCV Ab-positive rate was 8.4%. The HCV Ab-positive patients were more frequently female than their counterparts (66.7% vs. 40.8%, P =0.009). No HCV core-positive cells were found in the ECC tissues. In conclusion, HCV infection and age ≥49 years are potential risk factors for ECC. The HCV-associated ECC risk might not be reversed by interferon-based anti-HCV therapy nor associated with in situ HCV core-related carcinogenesis., Competing Interests: None., (AJCR Copyright © 2023.)

Background: The study aimed to assess the clinical characteristics of patients with nocardiosis, to evaluate the in vitro susceptibility of antimicrobial agents against Nocardia species, and to explore changes in antimicrobial susceptibilities in this era of multidrug resistance., Methods: Nocardia isolates were identified to the species level using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA, hsp65, and secA1 gene sequencing, and minimum inhibitory concentrations (MICs) of 15 antimicrobial agents were assessed with the broth microdilution method., Results: Eighty-nine isolates from 68 patients were identified to species level. The most common species were Nocardia brasiliensis (n = 28, 31.5%), followed by N. farcinica (n = 24, 27%) and N. cyriacigeorgica (n = 16, 18%). Skin and soft tissue were the most common sites of nocardiosis. In multivariate analysis, cutaneous infection (OR, 0.052; p = 0.009), immunosuppressant use (OR, 16.006; p = 0.013) and Charlson combidity index (OR, 1.522; p = 0.029) were significant predictors for death. In total, 98.9% isolates were susceptible to trimethoprim-sulfamethoxazole and linezolid. Further, the MIC range and resistance rate of all Nocardia species to ceftriaxone, imipenem, and amoxicillin-clavulanic acid were found to generally increase over time., Conclusion: Considering that trimethoprim-sulfamethoxazole is effective against most Nocardia species, it is the antibiotic of choice in Taiwan. Besides, amikacin, tigecycline, and linezolid showed high activity against Nocardia species and are thus good alternatives or additional therapies to treat nocardiosis, depending on patient's underlying conditions and site of infection., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Introduction: The clinical efficiency of cefoperazone/sulbactam (CPZ/SUL) against Escherichia coli bacteremia was unknown. This study aimed to explore the relationship between CPZ/SUL MIC values and clinical outcomes in Escherichia coli bacteremia., Methods: A multicenter, retrospective, observational cohort study was conducted in Taiwan between January 2015 and December 2020. Patients treated with CPZ/SUL for E. coli bacteremia were enrolled in the analysis. The CPZ/SUL MICs were determined by using the agar dilution method. The primary outcome was 30-day mortality., Results: Among 247 isolates, 160 (64.8%) isolates were susceptible, 8 (3.2%) were intermediate, and 79 (32.0%) were resistant to cefoperazone. The activity of cefoperazone against cefoperazone-non-susceptible E. coli (n = 87) was restored upon combination with sulbactam, with susceptibility ranging from 0% to 97.7%. The 30-day mortality was 4.5% (11/247) and overall clinical success rate was 91.9% (227/247). Multivariate Cox proportional-hazards model revealed that heart failure [adjusted relative risk (ARR), 5.49; 95% confidence interval (CI) 1.31-23.02; p = 0.020], malignancy (ARR 7.50; 95% CI 2.02-27.80; p = 0.003), SOFA score (ARR 1.29; 95% CI 1.09-1.52; p = 0.003), and CPZ/SUL MIC ≥ 64 mg/L (ARR 11.31; 95% CI 1.34-95.52; p = 0.026) were independently associated with 30-day mortality. No statistically significant differences in 30-day mortality were found between groups with or without cefoperazone susceptibility (3.4% vs. 5.0%, p = 0.751, respectively)., Conclusions: Patients with E. coli bacteremia who were treated with CPZ/SUL had a favorable outcome when the MICs of the isolates were ≤ 16 mg/L and a high risk of mortality with MICs ≥ 64 mg/L., (© 2022. The Author(s).)

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 (MIC 50/90 , 0.25/1 mg/L; 100% of isolates were inhibited at ≤4 mg/L) and CNSAB (MIC 50/90 , 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 (MIC 50/90 , 1/2 mg/L; 92.5% of CNSAB isolates were inhibited at ≤2 mg/L) and eravacycline (MIC 50/90 , 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 (MIC 50/90 , 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., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Whether hepatitis C virus (HCV) infection is associated with breast cancer risk remains elusive, and we aimed to elucidate it. A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database (TNHIRD) was conducted. Additionally, breast cancer risk factors, and HCV core expression were surveyed in breast cancer patients of a tertiary care center. Three TNHIRD cohorts (1:4:4, propensity score-matched, 2003-2012), including HCV-treated (3646 HCV-infected females with interferon-based therapy ≥6 months), HCV-untreated (n = 14,584) and HCV-uninfected (n = 14,584) cohorts, were enrolled. The HCV-untreated cohort had the highest 9-year breast cancer cumulative incidence (2.017%; 95% confidence interval [CI]: 1.382%-2.846%), while the HCV-treated (1.073%; 0.414%-2.356%), and HCV-uninfected (1.453%; 0.785%-2.486%) cohorts showed no difference. Untreated HCV infection (hazard ratio [HR]: 1.701; 95% CI: 1.205%-2.400), urban residency (1.658, 1.183-2.323), and baseline cardiovascular events (1.920; 1.005-3.668) were associated with incident breast cancers. The interaction analysis showed that particularly among patients <49 years, HCV infection was associated with breast cancer development (2.193; 1.097-4.384). Of 12,170 hospitalized breast cancer patients, 4.90% were HCV Ab-positive. HCV Ab-positive patients were older (60.92+/-10.82 vs 53.91+/-11.38 years, P < 0.0001) and had a higher body mass index (25.39+/-5.1 vs 24.5+/-4.3 kg/m 2 , P = 0.007), rates of diabetes (30.60 vs 19.98%, P < 0.0001), hypertension (46.9 vs 30.39%, P < 0.0001), dyslipidemia (25.52 vs 20.28%, P = 0.031), and hyperuricemia (11.38 vs 5.52%, P < 0.0001) than their counterparts. No HCV core-positive cells were demonstrated in breast cancer tissues. Conclusions: Untreated HCV infection, urbanization, and cardiovascular events were potential risk factors for breast cancer. The HCV-associated risk was most prominent among patients <49 years, might not be associated with in situ HCV core-related oncogenesis but with metabolic alterations, and was reversed by anti-HCV therapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background/purpose: Superspreading events (SSEs) are pivotal in the spread of SARS-CoV-2. This study aimed to investigate an SSE of COVID-19 in a hospital and explore the transmission dynamics and heterogeneity of SSE., Methods: We performed contact tracing for all close contacts in a cluster. We did nasopharyngeal or throat swabbing for SARS-CoV-2 by real-time RT-PCR. Environmental survey was performed. The epidemiological and clinical characteristics of the SSE were studied., Results: Patient 1 with congestive heart failure and cellulitis, who had onset of COVID-19 two weeks after hospitalization, was the index case. Patient 1 led to 8 confirmed cases, including four health care workers (HCW). Persons tested positive for SARS-CoV-2 were HCW (n = 4), patient 1's family (n = 2), an accompanying person of an un-infected in-patient (n = 1), and an in-patient admitted before the SSE (n = 1). The attack rate among the HCW was 3.2 % (4/127). Environmental survey confirmed contamination at the bed rails, mattresses, and sink in the room patient 1 stayed, suggesting fomite transmission. The index case's sputum remained positive on illness day 35. Except one asymptomatic patient, at least three patients acquired the infection from the index case at the pre-symptomatic period. The effective reproduction number (R t ) was 0.9 (8/9)., Conclusion: The host factor (heart failure, longer viral shedding), transmissibility of SARS-CoV-2 (R t , pre-symptomatic transmission), and possible multiple modes of transmission altogether contributed to the SSE. Rapid response and advance deployment of multi-level protection in hospitals could mitigate COVID-19 transmission to one generation, thereby reducing its impact on the healthcare system., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

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., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021. Published by Elsevier B.V.)

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) is highly contagious, with a potential to cause large nosocomial outbreaks in the hospital setting. We report the advance deployment of comprehensive, multi-level infection control measures in a 3,700-bed large hospital to prevent nosocomial outbreaks of COVID-19 during the pandemic., Methods: We implemented a series of dynamic infection control policies during the pandemic. A confirmed COVID-19 case was defined by positive real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. All healthcare worker (HCW) having symptoms or close contact with the confirmed case received the RT-PCR test., Results: A total of 5,722 patients were tested in our hospital from January to May 2020. Twenty-five patients were confirmed COVID-19, including two inpatients. A cluster of 4 HCWs with COVID-19 associated with the 2nd inpatient was identified in the early stage of epidemic. Our enhanced traffic control bundling, mask wearing, hand hygiene and environmental cleaning were reinforced after the outbreak. All other confirmed cases were identified at our outdoor quarantine station or epidemic clinic afterwards, and the results of testing for 146 symptomatic HCWs were all negative., Conclusions: Integrated teamwork, advance deployment of infection control measures and efficient diagnostic testing and response protected HCW and facilities from large SARS-CoV-2 outbreaks and preserved the capacity and function of the health care system during the pandemic., Competing Interests: Conflicts of interest All authors report no conflicts of interest relevant to this article., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to investigate the trends in serotypes and in vitro antimicrobial susceptibility of Streptococcus pneumoniae causing adult invasive pneumococcal disease (IPD) to dalbavancin, telavancin, tedizolid, eravacycline, omadacycline and other comparator antibiotics from 2017-2020 following implementation of the 13-valent pneumococcal conjugate vaccine (PCV-13) and during the COVID-19 (coronavirus disease 2019) pandemic., Methods: During the study period, 237 S. pneumoniae isolates were collected from non-duplicate patients, covering 15.0% of IPD cases in Taiwan. Antimicrobial susceptibility testing was performed using a Sensititre® system. A latex agglutination method (ImmuLex™ Pneumotest Kit) was used to determine serotypes., Results: Susceptibility rates were high for vancomycin (100%), teicoplanin (100%) and linezolid (100%), followed by ceftaroline (non-meningitis) (98.3%), moxifloxacin (94.9%) and quinupristin/dalfopristin (89.9%). MIC 50 and MIC 90 values of dalbavancin, telavancin, tedizolid, eravacycline and omadacycline were generally low. Non-vaccine serotype 23A was the leading cause of IPD across the adult age range. Isolates of serotype 15B were slightly fewer than those of PCV-13 serotypes in patients aged ≥65 years. The overall case fatality rate was 15.2% (36/237) but was especially high for non-PCV-13 serotype 15B (21.4%; 3/14). Vaccine coverage was 44.7% for PCV-13 and 49.4% for the 23-valent pneumococcal polysaccharide vaccine (PPSV-23), but was 57% for both PCV-13 and PPSV-23., Conclusion: The incidence of IPD was stationary after PCV-13 introduction and only dramatically decreased in the COVID-19 pandemic in 2020. The MIC 50 and MIC 90 values of dalbavancin, telavancin, tedizolid, eravacycline, omadacycline were generally low for S. pneumoniae causing adult IPD., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have high mortality rates. Disseminated intravascular coagulation has been reported in SJS/TEN patients. The influence of this lethal complication in patients with SJS/TEN is not well known., Objective: This study aimed to investigate the risk and outcomes of disseminated intravascular coagulation in patients with SJS/TEN., Methods: We analyzed the disseminated intravascular coagulation profiles of patients receiving a diagnosis of SJS/TEN between 2010 and 2019., Results: We analyzed 150 patients with SJS/TEN (75 with SJS, 22 with overlapping SJS/TEN, and 53 with TEN) and their complete disseminated intravascular coagulation profiles. Disseminated intravascular coagulation was diagnosed in 32 patients (21.3%), primarily those with TEN. It was significantly associated with systemic complications, including gastrointestinal bleeding, respiratory failure, renal failure, liver failure, infection, and bacteremia. Additionally, SJS/TEN patients with disseminated intravascular coagulation had elevated procalcitonin levels. Among patients with SJS/TEN, disseminated intravascular coagulation was associated with a greater than 10-fold increase in mortality (78.1% vs 7%)., Limitations: The study limitations include small sample size and a single hospital system., Conclusion: Disseminated intravascular coagulation is a potential complication of SJS/TEN and associated with higher mortality. Early recognition and appropriate management of this critical complication are important for patients with SJS/TEN., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Traditional Chinese Medicine (TCM) has been extensively used to ameliorate diseases in Asia for over thousands of years. However, owing to a lack of formal scientific validation, the absence of information regarding the mechanisms underlying TCMs restricts their application. After oral administration, TCM herbal ingredients frequently are not directly absorbed by the host, but rather enter the intestine to be transformed by gut microbiota. The gut microbiota is a microbial community living in animal intestines, and functions to maintain host homeostasis and health. Increasing evidences indicate that TCM herbs closely affect gut microbiota composition, which is associated with the conversion of herbal components into active metabolites. These may significantly affect the therapeutic activity of TCMs. Microbiota analyses, in conjunction with modern multiomics platforms, can together identify novel functional metabolites and form the basis of future TCM research.

Nontuberculous mycobacterial lung disease (NTM-LD) prevalence has been increasing over the recent decades. Numerous host factors are associated with NTM-LD development, including susceptible phenotypes such as ciliary defect and lung structural change, pulmonary clearance defect with poor clearance of secretions, and immune suppression. Specifically, regarding the susceptible host phenotypes without clear pathogenesis, a slender body, pectus excavatum, and postmenopausal female status are common. Also, decreased host immunity to NTM, especially T helper 1 cell responses is frequently observed. Even so, the underlying mechanisms remain unclear and relevant large-scale studies are lacking. Infections due to host genetics associated defects are mostly untreatable but rare in Asia, particularly Taiwan. Nevertheless, some risks for NTM-LD are controllable over disease progression. We suggest that clinicians first manage host factors and deal with the controllable characteristics of NTM-LD, followed by optimizing anti-NTM treatment. Further researches focusing on NTM-LD pathogenesis, especially the host-NTM interaction may advance understanding the nature of the disease and develop efficient therapeutic regimens., Competing Interests: Declaration of Competing Interest The authors do not have any conflicts of interest to declare., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Genitourinary tuberculosis (GUTB) is rare but fatal if not diagnosed early. The purpose of this study was to investigate the outcomes of GUTB in Taiwan., Methods: We retrospectively reviewed medical records of 57 patients who were diagnosed as GUTB from January 2002 to December 2016, over a 15-year period. Demographic data and clinical manifestations were recorded for analysis., Results: There were 37 males and 20 females with a median age of 71 years. Kidney (24.6%) was the most involved organ. Fever (56.1%) was the major presentation. Sixteen (28.1%) patients presented unfavorable outcome. Compared with the favorable outcome group, the unfavorable outcome group had more malignancy (p = 0.013), fever (p = 0.020), anemia (p = 0007), thrombocytopenia (p = 0.003), and hypoalbuminemia (p = 0.015). In a multivariate analysis, fever (odds ratio: 42.716, 95% confidence interval: 1.032-1767.569; p = 0.048) was identified as prognostic factors for unfavorable outcome., Conclusion: GUTB is often in advanced stages with a high mortality in Taiwan. Establishing a diagnosis is difficult and requires thorough investigation. Fever is associated with unfavorable outcome., (Copyright © 2018. Published by Elsevier B.V.)

Background: This multicenter retrospective cohort study aimed to compare the clinical presentations and evolution of acute hepatitis A (AHA) between human immunodeficiency virus (HIV)-infected patients and HIV-uninfected counterparts during the AHA outbreak., Methods: Clinical and laboratory data were collected from the medical records of the patients with AHA at the 14 hospitals around Taiwan between May 2015 and May 2017., Results: A total of 297 adult patients with AHA were included during the study period. Their mean age was 31.4 years (range, 19.0-76.1 years); 93.4% were men and 58.6% were men who have sex with men. Of 265 patients with known HIV serostatus, 166 (62.6%) were HIV infected. Compared with HIV-uninfected patients, HIV-infected patients had a lower peak alanine aminotransferase (ALT) level (median, 1312 vs 2014 IU/L, P = .003), less coagulopathy (6.0% vs 16.2%, P = .007), and less hepatomegaly or splenomegaly on imaging studies, but a higher rate of delayed resolution of hepatitis (38.8% vs 21.3%, P = .009). HIV-infected patients with plasma RNA load <1000 copies/mL while receiving combination antiretroviral therapy (cART) had a higher peak ALT level (median, 1420 vs 978 IU/L, P = .006) and less delay in resolution of hepatitis (30.6% vs 48.8%, P = .047) than patients without cART or with plasma RNA load ≥1000 copies/mL., Conclusions: During an AHA outbreak, HIV-infected patients had a lower severity, but delayed resolution, of AHA than HIV-uninfected patients. Better viral suppression by cART alleviated the impact of HIV infection on the disease course of AHA in HIV-infected patients.

Iron availability affects swarming and biofilm formation in various bacterial species. However, how bacteria sense iron and coordinate swarming and biofilm formation remains unclear. Using Serratia marcescens as a model organism, we identify here a stage-specific iron-regulatory machinery comprising a two-component system (TCS) and the TCS-regulated iron chelator 2-isocyano-6,7-dihydroxycoumarin (ICDH-Coumarin) that directly senses and modulates environmental ferric iron (Fe 3+ ) availability to determine swarming initiation and biofilm formation. We demonstrate that the two-component system RssA-RssB (RssAB) directly senses environmental ferric iron (Fe 3+ ) and transcriptionally modulates biosynthesis of flagella and the iron chelator ICDH-Coumarin whose production requires the pvc cluster. Addition of Fe 3+ , or loss of ICDH-Coumarin due to pvc deletion results in prolonged RssAB signaling activation, leading to delayed swarming initiation and increased biofilm formation. We further show that ICDH-Coumarin is able to chelate Fe 3+ to switch off RssAB signaling, triggering swarming initiation and biofilm reduction. Our findings reveal a novel cellular system that senses iron levels to regulate bacterial surface lifestyle.

Background and Purpose: Bacteroides fragilis is a virulent anaerobic pathogen, resulting in considerable mortality. This study was conducted to investigate the clinical characteristics, significance of polymicrobial bacteremia, and treatment outcomes of B. fragilis bacteremia., Methods: This retrospective analysis enrolled 199 adult patients with B. fragilis bacteremia, who were admitted to hospital between January 2004 and May 2007. Chi-squared and Fisher's exact tests were used for comparison. A p value of <0.05 was considered statistically significant., Results: 142 patients with B. fragilis bacteremia (71.4%) had at least 1 underlying disease. Malignancy was the commonest comorbidity (n = 62; 31.2%). Intra-abdominal infection accounted for 49.3% of the infection sources. Seventy seven patients (38.7%) had polymicrobial bacteremia and Escherichia coli was the most common concurrent isolate (n = 24). There was no significant difference in septic shock incidence and clinical outcome between the monomicrobial and polymicrobial groups. The overall 30-day crude mortality rate was 30.7%. Inappropriate early antimicrobial therapy did not affect outcome, but a higher mortality rate was noted for patients who never received appropriate antimicrobial therapy (55.2% vs 26.5%; p = 0.002). Independent risk factors for mortality were age 65 years and older (p = 0.010), malignancy (p = 0.001), shock (p < 0.001), thrombocytopenia (p = 0.026), and lack of surgical intervention (p = 0.035)., Conclusions: B. fragilis bacteremia causes a high mortality rate, especially for elderly people and patients with cancer. Clinicians should be alert to the infectious focus, and appropriate surgical intervention may be necessary to improve outcomes.

Background and Purpose: Diagnosis of renal or perinephric abscess is still a challenge for physicians. This study investigated the effect of location and size of abscess and the time of diagnosis on treatment outcomes., Methods: This retrospective analysis enrolled 159 adult patients with renal, perinephric or mixed-type (renal plus perinephric) abscess hospitalized between June 2001 and June 2006. The outcomes of these patients were classified into "poor" and "success" in order to elucidate associated risk factors. 106 patients had clear information of the timing of diagnosis and were categorized into "early" and "delayed" diagnosis groups, depending on whether the diagnosis was made within or after 5 days of admission., Results: Compared with the early diagnosis group (n = 78), the delayed diagnosis group (n = 28) were older (59.9 +/- 15.9 vs 50.9 +/- 14.9 years, p=0.005) and had less costovertebral angle knocking pain (85.7% vs 51.3%, p=0.021), a higher rate of renal insufficiency (57.1% vs 15.4%, p<0.001) and hospital stay over 22 days (71.4% vs 24.4%, p<0.001). There was no significant difference between these two groups in clinical outcomes. Compared with renal abscess, both perinephric and mixed-type abscess had higher rates of larger abscess (>5 cm in diameter) [84.1% vs 25.6%, p<0.001; and 55.6% vs 25.6%, p=0.012, respectively] and lower rates of Escherichia coli infection (24.4% vs 59.4%, p<0.001; and 26.7% vs 59.4%, p=0.021, respectively). Among all culture-positive patients, the proportion of Klebsiella pneumoniae was 25.6%. Perinephric abscess had higher rates of percutaneous (56.3% vs 31.5%; p=0.005) and surgical drainage (29.2% vs 7.6%; p=0.001) than renal abscess. In multivariate analysis, age > or =65 years (p=0.006; odds ratio [OR], 7.008; 95% confidence interval [CI], 1.75-28.141), thrombocytopenia (p=0.002; OR [95% CI], 10.434 [2.344-46.444]), and abscess without drainage (p=0.001; OR [95% CI], 9.984 [2.640-37.758]) were independent factors for poor outcome (mortality or nephrectomy)., Conclusion: Old age, renal insufficiency and lack of costovertebral angle knocking pain may contribute to delayed diagnosis of renal or perinephric abscess, and prolonged hospital stay. The location and size of abscess did not affect clinical outcome in this study, which might be due to adequate abscess drainage. K. pneumoniae is not uncommon in renal or perinephric abscess in Taiwan.

Background and Purpose: To characterize the clinical and microbiological features of tuberculous arthritis and to clarify the factors affecting treatment outcome., Methods: We retrospectively reviewed 51 adult patients with a diagnosis of tuberculous arthritis at Chang Gung Memorial Hospital-Linkou over a 14-year period., Results: There were 35 males and 16 females with a mean age of 58.9 years (range, 32 to 89 years). The mean duration of symptoms and signs before diagnosis was 25.4 months (range, 0.25 to 180 months). Joint pain (96.1%) and swelling (90.2%) were two major presentations. Forty five (88.2%) patients had monoarthritis. Knee (26.7%) was the most frequently involved one. Twenty six (51.0%) patients had roentgenologic evidence of pulmonary tuberculosis (TB). Forty three patients (84.3%) had positive TB culture of synovial fluid and/or tissue. Of which, 27 (63%) had positive acid-fast bacillus smear. Twenty five patients had sputum for mycobacterial smear and culture, and 17 of them had positive TB culture. Thirty six patients received post-treatment follow-up for 3 to 110 months. Among them, 8 had relapses and 28 had treatment success. Compared the relapse to the success, the former had a higher ratio of drug resistant strains (odds ratio, 7.8; 95% confidence interval, 1.025-59.337; p=0.047) and had a longer treatment duration (22.0 +/- 4.4 vs 13.2 +/- 4.1 months; p=0.001)., Conclusions: Tuberculous arthritis often occurred in elderly people with male predominance. Drug resistant strain may cause a relapse of tuberculous arthritis, which may result in longer treatment duration. Routine chest X-ray and sputum for mycobacterial smear and culture could be necessary to find concurrent pulmonary TB.

Background and Purpose: To investigate factors that might affect the sputum conversion and treatment outcome of Mycobacterium avium-intracellulare complex (MAC) pulmonary disease., Methods: This retrospective study reviewed 46 patients diagnosed with MAC pulmonary disease at the Chang Gung Memorial Hospital at Linkou between July 1998 and February 2005. The diagnosis was based on the American Thoracic Society criteria for diagnosis of disease due to non-tuberculous mycobacteria of 1997., Results: Of the 46 patients reviewed, 30 were men and 16 women, with a mean age of 64.39 years (range, 28-87 years). Thirty one patients had preexisting lung diseases, including history of pulmonary tuberculosis in 23 patients. Follow-up of sputum cultures could be traced in 28 patients, and sputum conversion was found in 17 patients. Of the 28 patients, 9 were treated with anti-MAC drugs for <5 months or with a regimen not containing at least 2 anti-MAC drugs. These treatment regimens were significantly associated with failure of sputum conversion to culture negativity (adjusted odds ratio [OR], 16.83; 95% confidence interval [CI], 1.16-245.06; p=0.039). Eleven of the remaining 19 patients were treated with an anti-MAC regimen containing clarithromycin for >5 months. However, there was no statistically significant association between sputum conversion and clarithromycin-containing anti-MAC regimens (OR, 0.42; 95% CI, 0.08-2.16; p=0.435)., Conclusions: MAC pulmonary disease often occurs in the context of preexisting lung disease, especially pulmonary tuberculosis. Patients tend to be older. Inappropriate treatment might lead to failure of sputum conversion. Treatment with rational combination regimens for at least 5 months could be necessary for sputum conversion.