Publications by authors named "Wen-Chien Ko"

453 Publications

In vitro activity of cefiderocol, cefepime/enmetazobactam, cefepime/zidebactam, eravacycline, omadacycline, and other comparative agents against carbapenem-non-susceptible Pseudomonas aeruginosa and Acinetobacter baumannii isolates associated from bloodstream infection in Taiwan between 2018-2020.

J Microbiol Immunol Infect 2021 Sep 4. Epub 2021 Sep 4.

Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Departments of Laboratory Medicine and Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan. Electronic address:

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, 0.25/1 mg/L; 100% of isolates were inhibited at ≤4 mg/L) and CNSAB (MIC, 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, 1/2 mg/L; 92.5% of CNSAB isolates were inhibited at ≤2 mg/L) and eravacycline (MIC, 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, 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.
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http://dx.doi.org/10.1016/j.jmii.2021.08.012DOI Listing
September 2021

Long-term neurological and healthcare burden of adults with Japanese encephalitis: A nationwide study 2000-2015.

PLoS Negl Trop Dis 2021 Sep 14;15(9):e0009703. Epub 2021 Sep 14.

Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Objective: To assess the healthcare utilization, economic burden, and long-term neurological complications and mortality of an adult population with Japanese encephalitis (JE).

Methods: This study utilized two nationwide datasets in Taiwan: the Notifiable Disease Dataset of confirmed cases from the Centers for Disease Control to identify JE patients, and the National Health Insurance Research Database to obtain patients' healthcare utilization. Survival analyses were performed to identify prognostic factors associated with the all-cause mortality of patients.

Results: This study included 352 adult cases with JE (aged≥20 years). The mean age of JE patients was 45 years. Stroke (event rate: 3.49/100 person-years) was the most common neurological complication, followed by epilepsy/convulsions (3.13/100 person-years), encephalopathy/delirium (2.20/100 person-years), and parkinsonism (1.97/100 person-years). Among the 336 hospitalized patients at JE diagnosis, 58.33% required intensive care. Among 79 patients who died following JE diagnosis, 48.84% of death events occurred within the year of diagnosis. The medical costs increased considerably at JE diagnosis and subsequent-year costs remained significantly higher than the costs before diagnosis (p<0.05). Having a four-dose JE vaccination (i.e., born after 1976) versus no JE vaccination history (i.e., born before 1963) was significantly associated with lower all-cause mortality (hazard ratio: 0.221 [95% confidence interval: 0.067, 0.725]). Comorbid diabetes and incident epilepsy/convulsion events significantly increased the mortality risk by 2.47- and 1.85-fold, respectively (p<0.05).

Conclusion: A considerable medical burden associated with JE was observed in affected adults, even in the years following JE diagnosis. Vaccination should be considered to prevent this sporadic, but lethal, viral infection.
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http://dx.doi.org/10.1371/journal.pntd.0009703DOI Listing
September 2021

Respiratory etiological surveillance among quarantined patients with suspected lower respiratory tract infection at a medical center in southern Taiwan during COVID-19 pandemic.

J Microbiol Immunol Infect 2021 Sep 1. Epub 2021 Sep 1.

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Infection Control Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:

Background: A comprehensive study of respiratory pathogens was conducted in an area with a low prevalence of COVID-19 among the adults quarantined at a tertiary hospital.

Methods: From March to May 2020, 201 patients suspected lower respiratory tract infection (LRTI) were surveyed for etiologies by multiplex polymerase chain reaction (PCR: FilmArray TM Respiratory Panel) test combination with cultural method, viral antigen detection and serologic surveys.

Results: Total 201 patients tested with FilmArray TM Respiratory Panel were enrolled, of which 68.2% had sputum bacterial culture, 86.1% had pneumococcus and Legionella urine antigen test. Their median age was 72.0 year-old with multiple comorbidities, and 11.4% were nursing home residents. Bacteria accounted for 59.7% of identified pathogens. Atypical pathogens were identified in 31.3% of total pathogens, of which viruses accounted for 23.9%. In comparison to patients with bacterial infection, patients with atypical pathogens were younger (median= 77.2 vs 67.1, years, P = 0.017) and had shorter length of hospital (8.0 vs 4.5, days, P = 0.007).

Conclusions: Patients with LRTI caused by atypical pathogens was indistinguishable from those with bacterial pathogens by clinical manifestations or biomarkers. Multiplex PCR providing rapid diagnosis of atypical pathogens enhance patient care and decision making when rate of sputum culture sampling was low in quarantine ward during pandemic.
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http://dx.doi.org/10.1016/j.jmii.2021.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423990PMC
September 2021

Multicenter surveillance of antimicrobial susceptibilities and resistance mechanisms among Enterobacterales species and non-fermenting Gram-negative bacteria from different infection sources in Taiwan from 2016 to 2018.

J Microbiol Immunol Infect 2021 Sep 3. Epub 2021 Sep 3.

Departments of Laboratory Medicine and Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan; Departments of Laboratory Medicine and Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jmii.2021.07.015DOI Listing
September 2021

Gut Dysbiosis during COVID-19 and Potential Effect of Probiotics.

Microorganisms 2021 Jul 28;9(8). Epub 2021 Jul 28.

Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 704, Taiwan.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus of the family , causes coronavirus disease 2019 (COVID-19), an influenza-like disease that chiefly infects the lungs through respiratory transmission. The spike protein of SARS-CoV-2, a transmembrane protein in its outer portion, targets angiotensin-converting enzyme 2 (ACE2) as the binding receptor for the cell entry. As ACE2 is highly expressed in the gut and pulmonary tissues, SARS-CoV-2 infections frequently result in gastrointestinal inflammation, with presentations ordinarily ranging from intestinal cramps to complications with intestinal perforations. However, the evidence detailing successful therapy for gastrointestinal involvement in COVID-19 patients is currently limited. A significant change in fecal microbiomes, namely dysbiosis, was characterized by the enrichment of opportunistic pathogens and the depletion of beneficial commensals and their crucial association to COVID-19 severity has been evidenced. Oral probiotics had been evidenced to improve gut health in achieving homeostasis by exhibiting their antiviral effects via the gut-lung axis. Although numerous commercial probiotics have been effective against coronavirus, their efficacies in treating COVID-19 patients remain debated. In ClinicalTrials.gov, 19 clinical trials regarding the dietary supplement of probiotics, in terms of and mixtures of and , for treating COVID-19 cases are ongoing. Accordingly, the preventive or therapeutic role of probiotics for COVID-19 patients can be elucidated in the near future.
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http://dx.doi.org/10.3390/microorganisms9081605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402052PMC
July 2021

infection: an emerging zoonosis?

Expert Rev Anti Infect Ther 2021 Aug 23:1-10. Epub 2021 Aug 23.

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Introduction: infection (CDI) is the most common cause of antibiotic-associated diarrhea and one of the common infections in healthcare facilities. In recent decades, there has been an emerging threat of community-acquired CDI (CA-CDI). Environmental transmission of in the community setting has become a major concern, and animals are an important reservoir for causing human diseases.

Areas Covered: In this article, the molecular epidemiology of in animals and recent evidences of zoonotic transfer to humans are reviewed based on an electronic search in the databases of PubMed and Google Scholar.

Expert Opinion: can be found in stool from diarrheal dogs and cats; therefore, household pets could be a potential source. will threaten human health because hypervirulent ribotype 078 strains have been found in retail chickens, pig farms, and slaughterhouses. Risk factors for fecal carriage in animals include young age, dietary changes, and antibiotic abuse in domestic animals. With the advent of whole genome sequencing techniques, there will be more solid evidence indicating zoonotic transfer of from animals to humans.
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http://dx.doi.org/10.1080/14787210.2021.1967746DOI Listing
August 2021

Blood Cultures and Appropriate Antimicrobial Administration after Achieving Sustained Return of Spontaneous Circulation in Adults with Nontraumatic Out-of-Hospital Cardiac Arrest.

Antibiotics (Basel) 2021 Jul 19;10(7). Epub 2021 Jul 19.

Department of Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

We aimed to determine the incidence of bacteremia and prognostic effects of prompt administration of appropriate antimicrobial therapy (AAT) on nontraumatic out-of-hospital cardiac arrest (OHCA) patients achieving a sustained return of spontaneous circulation (sROSC), compared with non-OHCA patients. In the multicenter case-control study, nontraumatic OHCA adults with bacteremia episodes after achieving sROSC were defined as case patients, and non-OHCA patients with community-onset bacteremia in the emergency department were regarded as control patients. Initially, case patients had a higher bacteremia incidence than non-OHCA visits (231/2171, 10.6% vs. 10,430/314,620, 3.3%; < 0.001). Compared with the matched control (2288) patients, case (231) patients experienced more bacteremic episodes due to low respiratory tract infections, fewer urosepsis events, fewer bacteremia, and more streptococcal and anaerobes bacteremia. Antimicrobial-resistant organisms, such as methicillin-resistant and extended-spectrum beta-lactamase-producing , were frequently evident in case patients. Notably, each hour delay in AAT administration was associated with an average increase of 10.6% in crude 30-day mortality rates in case patients, 0.7% in critically ill control patients, and 0.3% in less critically ill control patients. Conclusively, the incidence and characteristics of bacteremia differed between the nontraumatic OHCA and non-OHCA patients. The incorporation of blood culture samplings and rapid AAT administration as first-aids is essential for nontraumatic OHCA patients after achieving sROSC.
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http://dx.doi.org/10.3390/antibiotics10070876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300804PMC
July 2021

The Role of Toll-Like Receptor-2 in Infection: Evidence From a Mouse Model and Clinical Patients.

Front Immunol 2021 12;12:691039. Epub 2021 Jul 12.

Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.

Background: is the leading cause of nosocomial infectious diarrhea. Toll-like receptors (TLRs) are the major components of innate immunity that sense pathogens. The relationship between TLRs and infection (CDI) was analyzed in clinical patients and a mouse model.

Materials And Methods: A prospective investigation was conducted in medical wards of Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan, from January 2011 to January 2013. Adult patients were followed up for the development of CDI. Single nucleotide polymorphisms (SNPs) of TLR2 and TLR4 were analyzed to assess the relationship between genetic polymorphisms and the development of CDI. A mouse model of CDI was used to investigate the pathogenic role of TLRs in CDI, TLR2 and TLR4 knockout (Tlr2-/- and Tlr4-/-) mice.

Results: In the prospective study, 556 patients were enrolled, and 6.5% (36) of patients, accounting for 3.59 episodes per 1000 patient-days, developed CDI. Of 539 patients with available blood samples, the TLR2 rs3804099 polymorphism was more often noted in those with CDI than in those without CDI (64.5% 46.1%; = 0.046) but was not significant in multivariate analysis. Because the TLR2 rs3804099 polymorphism was moderately associated with CDI, the role of TLR2 and TLR4 was further evaluated in a mouse model. Both Tlr2-/- and Tlr4-/- mice showed more severe CDI disease than wild-type mice in terms of body weight change and fecal content five days after oral challenge with . Furthermore, Tlr2-/- mice suffered from more severe disease than Tlr4-/- mice, as evidenced by stool consistency, cecum weight, and survival rate.

Conclusion: The TLR2 rs3804099 polymorphism is marginally associated with the development of CDI, and the pathogenic role of TLR2 is further supported by a mouse model.
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http://dx.doi.org/10.3389/fimmu.2021.691039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313301PMC
July 2021

The Prevalence of Post-traumatic Stress Disorder Symptoms, Sleep Problems, and Psychological Distress Among COVID-19 Frontline Healthcare Workers in Taiwan.

Front Psychiatry 2021 12;12:705657. Epub 2021 Jul 12.

Department of Internal Medicine, Center for Infection Control, National Cheng Kung University Hospital, Tainan, Taiwan.

The adverse effect of COVID-19 pandemic among individuals has been very disturbing especially among healthcare workers. This study aims to examine the prevalence of post-traumatic stress disorder (PTSD) symptoms, sleep problems, and psychological distress among COVID-19 frontline healthcare workers in Taiwan. Hence, a total of 500 frontline healthcare workers were recruited to participate in this cross-sectional study. They responded to measures on fear of COVID-19, depression, anxiety, stress, insomnia, PTSD, perceived stigma, and self-stigma. The results indicated a prevalence rate of 15.4% for PTSD symptoms, 44.6% for insomnia, 25.6% for depressive symptoms, 30.6% for anxiety symptoms, and 23.4% for stress among the participants. There were significantly positive interrelationships between all these variables. Anxiety symptoms and fear of COVID-19 predicted PTSD whereas symptoms of anxiety, fear of COVID-19, and stress predicted insomnia. The prevalence rates of the psychological problems reveal a worrying view of mental health challenges among Taiwanese frontline healthcare workers. Anxiety symptoms and fear of COVID-19 are the common predictive factors of PTSD and sleep problems suggesting that mental healthcare services for them may help prevent future occurrence of psychological problems by allaying fears of healthcare workers. Therefore, there should be mental healthcare services for healthcare workers during the COVID-19 pandemic.
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http://dx.doi.org/10.3389/fpsyt.2021.705657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312888PMC
July 2021

Risk of non-typhoidal Salmonella vascular infections is increased with degree of atherosclerosis and inflammation: A multicenter study in southern Taiwan.

J Microbiol Immunol Infect 2021 Jun 21. Epub 2021 Jun 21.

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Infection Control Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Diagnostic Microbiology and Antimicrobial Resistance Laboratory, National Cheng Kung University Hospital, Tainan, Taiwan; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:

Background: Atherosclerosis and vascular inflammatory response have been considered as risk factors for non-typhoidal Salmonella (NTS) vascular infection. The study aims to assess the risk of vascular infection by measuring atherosclerosis severity, NTS vascular infection (NTSVI) score, and serum levels of inflammatory markers in people with NTS bacteremia.

Methods: A prospective observational study was conducted in two medical centers and two regional hospitals. Adults aged ≥50 years with NTS bacteremia who underwent computed tomography (CT) scan for revealing vascular infections were enrolled. The degree of atherosclerosis was scaled by a calcium score determined by a CT scan. Serum concentrations of inflammatory biomarkers were determined in the patients enrolled in a medical center.

Results: Fourteen (20.3%) of 69 patients with NTS bacteremia had vascular infections. Calcium scores over the thoracic (12,540 vs. 3,261, P = 0.0005) and abdominal (9755 vs. 3,461, P = 0.0006) aorta of those with vascular infections were higher than those without vascular infection. All vascular infections were present in the high-risk group (NTSVI score ≥1), yielding a sensitivity of 100% and specificity of 30.9%. Among 17 low-risk patients (NTSVI score <1), none had vascular infections, resulting in a negative predictive value of 100%. Higher plasma concentrations of IL-1β were detected in the cases of vascular infection than those in the control group (23.6 vs. 1.06 pg/mL, P = 0.001).

Conclusion: Atherosclerosis of the aorta which is associated with a positive NTSVI score can predict the occurrence of vascular infections and serum IL-1β could be a biomarker for vascular infection in patients with NTS bacteremia.
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http://dx.doi.org/10.1016/j.jmii.2021.04.007DOI Listing
June 2021

National surveillance of antimicrobial susceptibilities to dalbavancin, telavancin, tedizolid, eravacycline, omadacycline and other comparator antibiotics and serotype distribution of invasive Streptococcus pneumoniae isolates in adults: results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) programme in 2017-2020.

J Glob Antimicrob Resist 2021 Sep 18;26:308-316. Epub 2021 Jul 18.

Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Departments of Laboratory Medicine and Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan. Electronic address:

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 and MIC 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 and MIC values of dalbavancin, telavancin, tedizolid, eravacycline, omadacycline were generally low for S. pneumoniae causing adult IPD.
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http://dx.doi.org/10.1016/j.jgar.2021.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437679PMC
September 2021

Risk factors and clinical impact of bacteremia due to carbapenem-nonsusceptible Enterobacteriaceae: A multicenter study in southern Taiwan.

J Microbiol Immunol Infect 2021 Jun 25. Epub 2021 Jun 25.

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:

Background: The emergence of carbapenem-non-susceptible Enterobacteriaceae (CnSE) infections is a public health threat. This study investigated the risk factors and clinical impact of bacteremia due to CnSE.

Material And Methods: The study was conducted at three hospitals in southern Taiwan between January 1, 2017, and October 31, 2019. Only the first episode of CnSE bacteremia from each adult was included. For one episode of CnSE bacteremia, two subsequent bacteremic episodes due to carbapenem-susceptible Enterobacteriaceae isolates in each hospital were included as the controls.

Results: Among a total of 641 episodes of monomicrobial Enterobacteriaceae bacteremia were noted, 47 (7.3%) of which were of CnSE bacteremia. Ninety-four episodes of carbapenem-susceptible Enterobacteriaceae (CSE) bacteremia were selected as the controls for further analyses. In the multivariate analysis, hypertension (odds ratio [OR], 4.21; P = 0.005), Pitt bacteremia score (OR, 1.61; P = 0.002), and nosocomial bacteremia (OR, 3.30; P = 0.01) were associated with carbapenem nonsusceptibility among Enterobacteriaceae bacteremia. The most abundant CnSE isolate was Klebsiella pneumoniae (91.5%), followed by Klebsiella oxytoca (6.4%) and Escherichia coli (2.1%). Patients with CnSE bacteremia had a higher overall in-hospital mortality rate than those with CSE bacteremia (53.2% vs. 23.4%, P = 0.001). Moreover, in the multivariate analysis, the in-hospital mortality was significantly associated with higher Pitt bacteremia score (OR, 1.38; P = 0.02) and marginally associated with CnSE infections (OR, 2.44; P = 0.06).

Conclusion: Among adults with Enterobacteriaceae bacteremia, carbapenem nonsusceptibility, male sex, and the presence of hypertension or chronic kidney disease indicate a poor prognosis during hospitalization.
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http://dx.doi.org/10.1016/j.jmii.2021.05.005DOI Listing
June 2021

Inhibition of spores to prevent the recurrence of Clostridioides difficile infection - A possibility or an improbability?

J Microbiol Immunol Infect 2021 Jun 26. Epub 2021 Jun 26.

Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung Univeristy, Tainan, Taiwan. Electronic address:

Clostridioides difficile is one of the most common nosocomial gastrointestinal pathogens, and recurrence is a problematic issue because approximately 20-30% of patients experience at least one episode of recurrence, even after treatment with a therapeutic drug of choice for C. difficile infection (CDI), such as vancomycin. CDI recurrence has a multifactorial complex mechanism, in which gut microbiota disruption coincident with viable C. difficile spores, is considered the most important factor. The effectiveness of an anti-C. difficile antimicrobial agent against CDI cannot guarantee its inhibitory effect on C. difficile spores and vice versa. However, an antimicrobial agent, such as fidaxomicin, which has a good inhibitory effect on both C. difficile vegetative cells and spores is assumed to not only treat CDI but also prevent its recurrence. Prolonged adherence to the exosporium has been proposed as a possible mechanism of inhibiting spores, and as a result, redesigning anti-C. difficile antimicrobial agents with the ability to adhere to the exosporium may provide another pathway for the development of anti-C. difficile spore agents. For example, vancomycin lacks an inhibitory effect against C. difficile spores, but a vancomycin-loaded spore-targeting iron oxide nanoparticle that selectively binds to C. difficile spores has been developed to successfully delay spore germination. Some new antimicrobial agents in phase II clinical trials, including cadazolid and ridinilazole, have shown exceptional anti-C. difficile and spore-inhibiting effects that can be expected to not only treat CDI but also prevent its recurrence in the future.
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http://dx.doi.org/10.1016/j.jmii.2021.06.002DOI Listing
June 2021

Nationwide surveillance of antimicrobial resistance in invasive isolates of Streptococcus pneumoniae in Taiwan from 2017 to 2019.

J Microbiol Immunol Infect 2021 Jun 21. Epub 2021 Jun 21.

Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jmii.2021.05.008DOI Listing
June 2021

COVID-19 vaccines: concerns beyond protective efficacy and safety.

Expert Rev Vaccines 2021 08 5;20(8):1013-1025. Epub 2021 Jul 5.

Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

Introduction: Several vaccine candidates have been developed using different platforms, including nucleic acids (DNA and RNA), viral vectors (replicating and non-replicating), virus-like particles, peptide-based, recombinant proteins, live attenuated, and inactivated virus modalities. Although many of these vaccines are undergoing pre-clinical trials, several large clinical trials investigating the clinical efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines have produced promising findings.

Areas Covered: In this review, we provide a status update on COVID-19 vaccines currently undergoing clinical trials and discuss issues of concern beyond vaccine efficacy and safety, including dosing regimens, the mixed vaccine strategy, prior severe acute respiratory syndrome coronavirus-2 infection, antibody levels, cellular immunity and protection, variants of concern, COVID-19 vaccine distribution, vaccination willingness, herd immunity, immunity passports, and vaccine indications.

Expert Opinion: Four vaccines have obtained emergency use authorization, 87 are at the clinical development stage, and 186 are in pre-clinical development. While the knowledge and development of COVID-19 vaccines is rapidly expanding, the benefits of COVID-19 vaccines must outweigh the potential risks of adverse events. To combat the COVID-19 pandemic, clinicians should consistently update COVID-19-associated information, and healthcare authorities and manufacturers should work together to provide adequate and appropriate vaccinations for the prevention of COVID-19.

Plain Language Summary: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic: the coronavirus disease 2019 (COVID-19) outbreak. The development and implementation of the COVID-19 vaccine could be an important measure to control the COVID-19 pandemic.Several phase 3 clinical trials have demonstrated the effectiveness and safety of COVID-19 vaccines for the prevention of SARS-CoV-2 infections. Several COVID-19 vaccines have obtained emergency use authorization and been implemented in many countries. Although concerns regarding unusual blood clots and low platelet counts have been raised, the benefits of COVID-19 vaccines outweigh the potential risks of adverse events.Except for children, the COVID-19 vaccine is recommended for all people, including those pregnant or immunocompromised. Healthcare authorities should advise people receiving the vaccine that they must seek medical attention if they have associated thromboembolism and thrombocytopenia symptoms. More studies are necessary to determine the appropriate vaccine dose and regimen strategy, as well as the effectiveness of COVID-19 vaccines against variants of concerns. A global effort must be made to achieve widespread vaccination and herd immunity.
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http://dx.doi.org/10.1080/14760584.2021.1949293DOI Listing
August 2021

COVID-19 vaccines and thrombosis with thrombocytopenia syndrome.

Expert Rev Vaccines 2021 08 8;20(8):1027-1035. Epub 2021 Jul 8.

Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

Introduction: To combat COVID-19, scientists all over the world have expedited the process of vaccine development. Although interim analyses of clinical trials have demonstrated the efficacy and safety of COVID-19 vaccines, a serious but rare adverse event, thrombosis with thrombocytopenia syndrome (TTS), has been reported following COVID-19 vaccination.

Areas Covered: This review, using data from both peer-reviewed and non-peer-reviewed studies, aimed to provide updated information about the critical issue of COVID-19 vaccine-related TTS.

Expert Opinion: : The exact epidemiological characteristics and possible pathogenesis of this adverse event remain unclear. Most cases of TTS developed in women within 2 weeks of the first dose of vaccine on the receipt of the ChAdOx1 nCoV-19 and Ad26.COV2.S vaccines. In countries with mass vaccination against COVID-19, clinicians should be aware of the relevant clinical features of this rare adverse event and perform related laboratory and imaging studies for early diagnosis. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) and intravenous immunoglobulins are recommended for the treatment of TTS. However, further studies are required to explore the underlying mechanisms of this rare clinical entity.

Plain Language Summary: Thrombosis with thrombocytopenia syndrome (TTS) usually develops within 2 weeks of the first doses of the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines.TTS mainly occurs in patients aged < 55 years and is associated with high morbidity and mortality.TTS mimics autoimmune heparin-induced thrombocytopenia and can be mediated by platelet-activating antibodies against platelet factor 4. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) should be considered as the treatment of choice if the platelet count is > 50 × 10/L and there is no serious bleeding. Intravenous immunoglobulins and glucocorticoids may help increase the platelet count within days and reduce the risk of hemorrhagic transformation when anticoagulation is initiated.TTS should be a serious concern during the implementation of mass COVID-19 vaccination, and patients should be educated about this complication along with its symptoms such as severe headache, blurred vision, seizure, severe and persistent abdominal pain, painful swelling of the lower leg, and chest pain or dyspnea. The incidence of TTS is low; therefore, maintenance of high vaccination coverage against COVID-19 should be continued.
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http://dx.doi.org/10.1080/14760584.2021.1949294DOI Listing
August 2021

In-vitro activity of cefiderocol, cefepime/zidebactam, cefepime/enmetazobactam, omadacycline, eravacycline and other comparative agents against carbapenem-nonsusceptible Enterobacterales: results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) in 2017-2020.

Int J Antimicrob Agents 2021 Sep 21;58(3):106377. Epub 2021 Jun 21.

Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address:

This study examined the susceptibility of carbapenem-nonsusceptible Enterobacterales (CNSE) to cefiderocol, cefepime/zidebactam, cefepime/enmetazobactam, omadacycline, eravacycline and other comparative agents. Non-duplicate Enterobacterales isolates from 16 Taiwanese hospitals were evaluated. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibility results were interpreted based on relevant guidelines. In total, 201 CNSE isolates were investigated, including 26 Escherichia coli isolates and 175 Klebsiella pneumoniae isolates. Carbapenemase genes were detected in 15.4% (n=4) of E. coli isolates and 47.4% (n=83) of K. pneumoniae isolates, with the most common being bla (79.3%, 69/87), followed by bla (13.8%, 12/87). Cefiderocol was the most active agent against CNSE; only 3.8% (n=1) of E. coli isolates and 4.6% (n=8) of K. pneumoniae isolates were not susceptible to cefiderocol. Among the carbapenem-resistant E. coli and K. pneumoniae isolates, 88.5% (n=23) and 93.7% (n=164), respectively, were susceptible to ceftazidime/avibactam. For cefepime/zidebactam, 23 (88.5%) E. coli isolates and 155 (88.6%) K. pneumoniae isolates had MICs ≤2/2 mg/L. For cefepime/enmetazobactam, 22 (84.6%) E. coli isolates and 85 (48.6%) K. pneumoniae isolates had MICs ≤2/8 mg/L. The higher MICs of K. pneumoniae against cefepime/enmetazobactam were due to only one (1.5%) of the 67 bla-carrying isolates being susceptible. MICs of omadacycline were significantly higher than those of eravacycline and tigecycline. In summary, cefiderocol, ceftazidime/avibactam and cefepime/zidebactam were more effective against carbapenem-nonsusceptible E. coli and K. pneumoniae than other drugs, highlighting their potential as valuable therapeutics.
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http://dx.doi.org/10.1016/j.ijantimicag.2021.106377DOI Listing
September 2021

Community-onset Clostridioides difficile infection in a pregnant woman without traditional risk factors.

J Microbiol Immunol Infect 2021 May 29. Epub 2021 May 29.

Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Centre for Infection Control, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jmii.2021.03.023DOI Listing
May 2021

Clostridioides difficile spores stimulate inflammatory cytokine responses and induce cytotoxicity in macrophages.

Anaerobe 2021 Aug 31;70:102381. Epub 2021 May 31.

Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA; Oklahoma State University College of Osteopathic Medicine at Cherokee Nation, Tahlequah, OK, USA. Electronic address:

Clostridioides difficile is a gram-positive, spore-forming anaerobic bacterium, and the leading cause of antibiotic-associated diarrhea worldwide. During C. difficile infection, spores germinate in the presence of bile acids into vegetative cells that subsequently colonize the large intestine and produce toxins. In this study, we demonstrated that C. difficile spores can universally adhere to, and be phagocytosed by, murine macrophages. Only spores from toxigenic strains were able to significantly stimulate the production of inflammatory cytokines by macrophages and subsequently induce significant cytotoxicity. Spores from the isogenic TcdA and TcdB double mutant induced significantly lower inflammatory cytokines and cytotoxicity in macrophages, and these activities were restored by pre-exposure of the spores to either toxins. These findings suggest that during sporulation, spores might be coated with C. difficile toxins from the environment, which could affect C. difficile pathogenesis in vivo.
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http://dx.doi.org/10.1016/j.anaerobe.2021.102381DOI Listing
August 2021

Application of Microbiome Management in Therapy for Infections: From Fecal Microbiota Transplantation to Probiotics to Microbiota-Preserving Antimicrobial Agents.

Pathogens 2021 May 24;10(6). Epub 2021 May 24.

Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan 700, Taiwan.

Oral vancomycin and metronidazole, though they are the therapeutic choice for infections (CDIs), also markedly disturb microbiota, leading to a prolonged loss of colonization resistance to after therapy; as a result, their use is associated with a high treatment failure rate and high recurrent rate. An alternative for CDIs therapy contains the delivery of beneficial (probiotic) microorganisms into the intestinal tract to restore the microbial balance. Recently, mixture regimens containing species, , or have been extensively studied for the prophylaxis of CDIs. Fecal microbiota transplantation (FMT), the transfer of (processed) fecal material from healthy donors to patients for treating CDIs, combined with vancomycin was recommended as the primary therapy for multiple recurrent CDIs (rCDIs). Either probiotics or FMT have been utilized extensively in preventing or treating CDIs, aiming at less disturbance in the microbiota to prevent rCDIs after therapy cessation. Otherwise, many newly developed therapeutic agents have been developed and aim to preserve microbiota during CDI treatment to prevent disease recurrence and might be useful in clinical patients with rCDIs in the future.
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http://dx.doi.org/10.3390/pathogens10060649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225043PMC
May 2021

Screening for Cryptococcal Antigenemia and Burden of Cryptococcosis at the Time of HIV Diagnosis: A Retrospective Multicenter Study.

Infect Dis Ther 2021 Sep 29;10(3):1363-1377. Epub 2021 May 29.

Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan.

Introduction: Screening for cryptococcal antigen (CrAg) is recommended for people living with HIV (PLWH) who present with low CD4 lymphocyte counts. Real-world experience is important to identify gaps between the guidelines and clinical practice. We investigated the trends of CrAg testing and prevalence of cryptococcal antigenemia among PLWH at the time of HIV diagnosis and the related mortality in Taiwan from 2009 to 2018.

Methods: Medical records of newly diagnosed PLWH seeking care at six medical centers around Taiwan between 2009 and 2018 were reviewed. The annual trends of PLWH who had CrAg testing and cryptococcal antigenemia were examined by Cochran-Armitage test. Among PLWH with CD4 < 200 cells/µl, timing of CrAg testing was analyzed for association with 12-month all-cause mortality in Kaplan-Meier plots and in a Cox proportional hazards model after adjustments.

Results: Among 5372 included PLWH, 1150 (21.4%) presented with baseline CD4 < 100 cells/µl, and this proportion had decreased during the study period [from 108 (29.3%) in 2009 to 93 (22.3%) in 2018 (P = 0.039)]. The overall prevalence of cryptococcal antigenemia was 7.8% among PLWH with CD4 < 100 cells/µl, which remained stable during the 10-year study period (P = 0.356) and was 2.6% among PLWH with CD4 100-199 cells/µl. The uptake of CrAg testing had increased from 65.7% in 2009 to 78.0% in 2018 (P = 0.002) among PLWH with CD4 < 100 cells/µl. Late CrAg testing, defined by 14 days or later after HIV diagnosis, was associated with increased risk of 12-month mortality compared to early CrAg testing (adjusted hazard ratio 2.028, 95% CI 1.109-3.708).

Conclusions: Burden of cryptococcosis remained high among PLWH with low CD4 lymphocyte counts in Taiwan. Uptake of CrAg screening among late HIV presenters was still suboptimal and delayed. Late CrAg testing was associated with a higher mortality.
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http://dx.doi.org/10.1007/s40121-021-00451-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322196PMC
September 2021

Carbapenem-Resistant Enterobacterales in Long-Term Care Facilities: A Global and Narrative Review.

Front Cell Infect Microbiol 2021 23;11:601968. Epub 2021 Apr 23.

Division of Infectious Disease, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

The emergence of carbapenem-resistant Enterobacterales (CRE) has become a major public health concern. Moreover, its colonization among residents of long-term care facilities (LTCFs) is associated with subsequent infections and mortality. To further explore the various aspects concerning CRE in LTCFs, we conducted a literature review on CRE colonization and/or infections in long-term care facilities. The prevalence and incidence of CRE acquisition among residents of LTCFs, especially in California, central Italy, Spain, Japan, and Taiwan, were determined. There was a significant predominance of CRE in LTCFs, especially in high-acuity LTCFs with mechanical ventilation, and thus may serve as outbreak centers. The prevalence rate of CRE in LTCFs was significantly higher than that in acute care settings and the community, which indicated that LTCFs are a vital reservoir for CRE. The detailed species and genomic analyses of CRE among LTCFs reported that is the primary species in the LTCFs in the United States, Spain, and Taiwan. KPC-2-containing strains with sequence type 258 is the most common sequence type of KPC-producing in the LTCFs in the United States. IMP-11- and IMP-6-producing CRE were commonly reported among LTCFs in Japan. OXA-48 was the predominant carbapenemase among LTCFs in Spain. Multiple risk factors associated with the increased risk for CRE acquisition in LTCFs were found, such as comorbidities, immunosuppressive status, dependent functional status, usage of gastrointestinal devices or indwelling catheters, mechanical ventilation, prior antibiotic exposures, and previous culture reports. A high CRE acquisition rate and prolonged CRE carriage duration after colonization were found among residents in LTCFs. Moreover, the patients from LTCFs who were colonized or infected with CRE had poor clinical outcomes, with a mortality rate of up to 75% in infected patients. Infection prevention and control measures to reduce CRE in LTCFs is important, and could possibly be controlled active surveillance, contact precautions, cohort staffing, daily chlorhexidine bathing, healthcare-worker education, and hand-hygiene adherence.
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http://dx.doi.org/10.3389/fcimb.2021.601968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102866PMC
June 2021

Antimicrobial susceptibility of bacteremic vancomycin-resistant Enterococcus faecium to eravacycline, omadacycline, lipoglycopeptides, and other comparator antibiotics: Results from the 2019-2020 Nationwide Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART).

Int J Antimicrob Agents 2021 Jul 5;58(1):106353. Epub 2021 May 5.

Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address:

Multicenter surveillance of antimicrobial susceptibility was performed for 235 vancomycin-resistant Enterococcus faecium (VREfm) isolates from 18 Taiwanese hospitals. The minimum inhibitory concentrations (MICs) of eravacycline, omadacycline, lipoglycopeptides, and other comparator antibiotics were determined using the broth microdilution method. Nearly all isolates of VREfm were not susceptible to teicoplanin, dalbavancin, and telavancin, with susceptibility rates of 0.5%, 1.7% and 0.5%, respectively. Tigecycline and eravacycline were active against 93.2% and 89.7% of the VREfm isolates, respectively. Moreover, the susceptibility rates of quinupristin/dalfopristin, tedizolid, and linezolid were 59.1%, 84.2%, and 77.4%, respectively. Additionally, 94% of the VREfm isolates were classified as susceptible to daptomycin, and the MICs of omadacycline required to inhibit VREfm growth by 50% and 90% were 0.12 and 0.5 mg/L, respectively. Susceptibility rates of VREfm isolates to synthetic tetracyclines and daptomycin were slightly lower and to oxazolidinone-class antibiotics were much lower in Taiwan than those in other parts of the world. Continuous monitoring of VREfm resistance to novel antibiotics, including synthetic tetracyclines, oxazolidinone-class antibiotics, and daptomycin, is needed in Taiwan.
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http://dx.doi.org/10.1016/j.ijantimicag.2021.106353DOI Listing
July 2021

Temporal Trend of ST131 Clone among Urinary Isolates in the Community: A Taiwan National Surveillance from 2002 to 2016.

Microorganisms 2021 Apr 29;9(5). Epub 2021 Apr 29.

National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 350, Taiwan.

Sequence type (ST) 131 is a multidrug-resistant pandemic lineage of responsible for extraintestinal infections. Few surveillance data of ST131 included all antimicrobial-susceptible and -resistant isolates or focused on community-acquired urinary tract infection (UTI). From a population-based surveillance pool of 2997 outpatient urine isolates, 542 were selected for detection of ST131 based on ciprofloxacin and/or cefotaxime resistance. Pulsed-field gel electrophoresis (PFGE) was performed on all ST131 isolates to further determine their relatedness. The estimated overall ST131 prevalence in this community UTI cohort increased from 11.2% (in 2002-2004), 12.2% (in 2006-2008), 13.6% (in 2010-2012), to 17.4% in 2014-2016 ( < 0.01). In the ciprofloxacin-resistant/cefotaxime-resistant group, ST131 increased from 33.3% in 2002-2004 to 72.1% in 2014-2016 ( < 0.01). In the ciprofloxacin-resistant/cefotaxime-susceptible group, ST131 was found in 24.3% overall without significant increase in its prevalence over time. PFGE showed emergence of a cluster of ciprofloxacin-resistant/cefotaxime-resistant ST131 carrying Gr. 1 CTX-M ESBL in 2014-2016, especially 2016. Multivariate analysis revealed that age (≥65 y.o) and ciprofloxacin resistance were independent factors associated with ST131. This longitudinal surveillance showed that ciprofloxacin-resistant/cefotaxime-susceptible ST131 has been circulating in the community since 2002 but ciprofloxacin-resistant/cefotaxime-resistant ST131 increased rapidly in the later years.
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http://dx.doi.org/10.3390/microorganisms9050963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145988PMC
April 2021

Causes of death among dengue patients causes of death among hospitalized adults with dengue fever in Tainan, 2015: Emphasis on cardiac events and bacterial infections.

J Microbiol Immunol Infect 2021 Apr 9. Epub 2021 Apr 9.

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan; Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:

Introduction: The 2015 dengue outbreak in southern Taiwan caused substantial mortality. We analyzed the causes of death among these patients.

Materials And Methods: This retrospective study was conducted at a medical center in Tainan from August 2015 to December 2015. Dengue was diagnosed based on the detection of serum dengue NS1 antigen, IgM, or viral RNA in the blood. Causes of death were retrieved from chart reviews by three clinicians.

Results: There were 4488 cases of dengue in the study hospital, with an in-hospital fatality rate of 1.3% (60 cases). The mean age of the 60 fatal cases was 73 years, among whom 90% were aged ≥65 years. Twenty-eight (46.7%) patients died of severe dengue, and 29 (48.3%) deaths were possibly related to dengue. Of the latter, 24 (40%) died of secondary infections. Thirteen cardiac arrest events, including out-of-hospital (5 events) and in-hospital (8) cardiac arrests in the emergency department, occurred during the dengue epidemic. Seven (53.8%) patients did not receive medical aid before the event. Of the 40 deaths that occurred within one week after hospitalization, 60% died of severe dengue. In contrast, 50% of 20 deaths that occurred one week after hospitalization were related to hospital-acquired infections, mainly pneumonia.

Conclusion: Of 60 fatal cases, with a predominance of elderly patients, deaths were related to severe dengue within the first week after admission and secondary infections thereafter. The absence of medical care before cardiac arrest events highlights the importance of health education for warning signs of dengue.
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http://dx.doi.org/10.1016/j.jmii.2021.03.010DOI Listing
April 2021

A seroprevalence study of COVID-19 at a campus in southern Taiwan.

J Microbiol Immunol Infect 2021 Apr 8. Epub 2021 Apr 8.

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jmii.2021.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028599PMC
April 2021

Willingness of Taiwan's Healthcare Workers and Outpatients to Vaccinate against COVID-19 during a Period without Community Outbreaks.

Vaccines (Basel) 2021 Mar 12;9(3). Epub 2021 Mar 12.

Center for Infection Control, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

To control the spread of the novel coronavirus disease 2019 (COVID-19), COVID-19 vaccination has been quickly developed. However, the COVID-19 pandemic will not be controlled if the COVID-19 vaccination uptake willingness is low. Therefore, the study aim was to explore the COVID-19 vaccination uptake willingness among the outpatient population and healthcare workers in Taiwan during the worldwide pandemic period without community outbreaks. A cross-sectional survey was conducted among healthcare workers (HCWs; = 500; mean age = 32.96 years) of National Cheng Kung University Hospital (NCKUH) and outpatients ( = 238; mean age = 34.43 years) arriving at NCKUH. We used an online survey conducted between September 24 and 21 November 2020, for healthcare workers, and between 27 October and 31 December 2020, for the outpatient sample. Information regarding willingness to receive vaccination, willingness to rapid test, fear of COVID-19, risk perception, and preventive behaviors was collected in both samples; information regarding willingness to care for patients was collected in healthcare workers. Willingness to receive vaccination was the main variable in the present study; willingness to rapid test, willingness to care for patients, fear of COVID-19, risk perception, and preventive behaviors were the secondary variables in the study. The factors associated with vaccination willingness were identified through logistic regression analysis. The participants' willingness to receive vaccination was low for both healthcare workers (23.4%) and the outpatient sample (30.7%). Similarly, their willingness to take rapid tests was low (23.6% for healthcare workers and 28.6% for outpatient sample). Risk perception (crude odds ratio (COR) = 1.29; 95% confidence interval (CI) = 1.03, 1.63), willingness to take rapid test (COR = 9.24; 95% CI = 5.76, 14.83), and preventive COVID-19 infection behaviors (COR = 2.32; 95% CI = 1.52, 3.56) were significant factors explaining the healthcare workers' willingness to receive vaccination. Willingness to take a rapid test (COR = 8.91; 95% CI = 4.71, 16.87) and preventive COVID-19 infection behaviors (COR = 1.69; 95% CI = 1.09, 2.60) were significant factors explaining the outpatient sample's willingness to receive vaccination. Willingness to vaccinate against COVID-19 among HCWs and outpatients is low due to the relatively safe status of COVID-19 infection in Taiwan. These findings can help policymakers advocate for the effectiveness of and provide transparent information on COVID-19 vaccination uptake in a country/region with a relatively safe COVID-19 outbreak status.
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http://dx.doi.org/10.3390/vaccines9030246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000386PMC
March 2021

A Large Spatial Survey of Colistin-Resistant Gene -Carrying in Rivers across Taiwan.

Microorganisms 2021 Mar 31;9(4). Epub 2021 Mar 31.

Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan.

Background: Colistin is one of the last-line antimicrobial agents against life-threatening infections. The distribution of the colistin resistance gene has been reported worldwide. However, most studies have focused on the distribution of -positive bacteria in humans, animals, food, and sewage; few have focused on their distribution in natural environments.

Method: We conducted a large spatial survey of -positive at 119 sites in 48 rivers, covering the entire island of Taiwan. We investigated the relationship between the livestock or poultry density in the surveyed riverine area and the number of -positive in the river water. We then sequenced and characterized the isolated -positive plasmids.

Results: Seven positive were isolated from 5.9% of the sampling sites. The -positive sites correlated with high chicken and pig stocking densities but not human population density or other river parameters. Four of the -positive strains harbored epidemic IncX4 plasmids, and three of them exhibited identical sequences with a size of 33,309 bp. One of the plasmids contained identical 33,309 bp sequences but carried an additional 5711-bp transposon (Tn3 family). To our knowledge, this is the first demonstration that -carrying IncX4 plasmids can contain an insertion of such transposons. All -positive isolates belonged to phylogenetic group A and harbored few known virulence genes.

Conclusion: This study showed a positive relationship between the number of -positive sites and high livestock and poultry density. The sequencing analyses indicated that the epidemic plasmid in the isolates circulates not only in humans, animals, and food but also in the associated environments or natural habitats in Taiwan, suggesting that the surveillance of antibiotics-resistance genes for livestock or poultry farm quality control should include their associated environments.
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http://dx.doi.org/10.3390/microorganisms9040722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066897PMC
March 2021

Association of fluoroquinolones use with the risk of aortic aneurysm or aortic dissection: Facts and myths.

J Microbiol Immunol Infect 2021 Apr 14;54(2):182-184. Epub 2021 Mar 14.

Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jmii.2021.03.002DOI Listing
April 2021
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