Publications by authors named "Po-Ren Hsueh"

764 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

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

Animal Coronavirus Diseases: Parallels with COVID-19 in Humans.

Viruses 2021 07 30;13(8). Epub 2021 Jul 30.

Faculty of Veterinary Medicine, Universiti Putra Malaysia, UPM, Serdang 43400, Selangor, Malaysia.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus in humans, has expanded globally over the past year. COVID-19 remains an important subject of intensive research owing to its huge impact on economic and public health globally. Based on historical archives, the first coronavirus-related disease recorded was possibly animal-related, a case of feline infectious peritonitis described as early as 1912. Despite over a century of documented coronaviruses in animals, the global animal industry still suffers from outbreaks. Knowledge and experience handling animal coronaviruses provide a valuable tool to complement our understanding of the ongoing COVID-19 pandemic. In this review, we present an overview of coronaviruses, clinical signs, COVID-19 in animals, genome organization and recombination, immunopathogenesis, transmission, viral shedding, diagnosis, treatment, and prevention. By drawing parallels between COVID-19 in animals and humans, we provide perspectives on the pathophysiological mechanisms by which coronaviruses cause diseases in both animals and humans, providing a critical basis for the development of effective vaccines and therapeutics against these deadly viruses.
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http://dx.doi.org/10.3390/v13081507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402828PMC
July 2021

Global guideline for the diagnosis and management of rare yeast infections: an initiative of the ECMM in cooperation with ISHAM and ASM.

Lancet Infect Dis 2021 Aug 19. Epub 2021 Aug 19.

Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Uncommon, or rare, yeast infections are on the rise given increasing numbers of patients who are immunocompromised or seriously ill. The major pathogens include those of the genera Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon (ie, basidiomycetes) and Kodamaea, Malassezia, Pseudozyma (ie, now Moesziomyces or Dirkmeia), Rhodotorula, Saccharomyces, and Sporobolomyces (ie, ascomycetes). A considered approach to the complex, multidisciplinary management of infections that are caused by these pathogens is essential to optimising patient outcomes; however, management guidelines are either region-specific or require updating. In alignment with the One World-One Guideline initiative to incorporate regional differences, experts from diverse geographical regions analysed publications describing the epidemiology and management of the previously mentioned rare yeasts. This guideline summarises the consensus recommendations with regards to the diagnostic and therapeutic options for patients with these rare yeast infections, with the intent of providing practical assistance in clinical decision making. Because there is less clinical experience of patients with rare yeast infections and studies on these patients were not randomised, nor were groups compared, most recommendations are not robust in their validation but represent insights by use of expert opinions and in-vitro susceptibility results. In this Review, we report the key features of the epidemiology, diagnosis, antifungal susceptibility, and treatment outcomes of patients with Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon spp infections.
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http://dx.doi.org/10.1016/S1473-3099(21)00203-6DOI Listing
August 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

Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) Analysis for the Identification of Pathogenic Microorganisms: A Review.

Microorganisms 2021 Jul 19;9(7). Epub 2021 Jul 19.

Departments of Laboratory Medicine and Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung 40447, Taiwan.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been used in the field of clinical microbiology since 2010. Compared with the traditional technique of biochemical identification, MALDI-TOF MS has many advantages, including convenience, speed, accuracy, and low cost. The accuracy and speed of identification using MALDI-TOF MS have been increasing with the development of sample preparation, database enrichment, and algorithm optimization. MALDI-TOF MS has shown promising results in identifying cultured colonies and rapidly detecting samples. MALDI-TOF MS has critical research applications for the rapid detection of highly virulent and drug-resistant pathogens. Here we present a scientific review that evaluates the performance of MALDI-TOF MS in identifying clinical pathogenic microorganisms. MALDI-TOF MS is a promising tool in identifying clinical microorganisms, although some aspects still require improvement.
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http://dx.doi.org/10.3390/microorganisms9071536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304613PMC
July 2021

Comparison of Etest and broth microdilution for evaluating the susceptibility of Staphylococcus aureus and Streptococcus pneumoniae to ceftaroline and of carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa to ceftazidime/avibactam.

J Glob Antimicrob Resist 2021 Jul 22;26:301-307. Epub 2021 Jul 22.

Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal 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: Decreased susceptibility to ceftazidime/avibactam (CZA) and ceftaroline (CPT) has been reported during antimicrobial resistance surveillance and therapy. Conventional laboratories are unable to provide timely susceptibility testing for CZA and CPT because these antimicrobial agents are not incorporated in automated susceptibility testing systems.

Methods: We evaluated Etest and the Sensititre broth microdilution (BMD) method for testing CZA against carbapenem-resistant Gram-negative bacilli and CPT against important Gram-positive cocci bloodstream isolates. Genotypes of carbapenemases in Enterobacterales were also determined using the Xpert® Carba-R assay.

Results: Etest showed ≥90% agreement with Sensititre BMD for carbapenem-resistant Klebsiella pneumoniae (CRKP) (n = 187), carbapenem-resistant Escherichia coli (CREC) (n = 28) and Streptococcus pneumoniae (n = 35); however, the very major error rate exceeded 3%. Agreement between Etest and Sensititre BMD was <90% for carbapenem-resistant Pseudomonas aeruginosa (CRPA) (n = 81), methicillin-susceptible Staphylococcus aureus (MSSA) (n = 92) and methicillin-resistant S. aureus (MRSA) (n = 170). Both agents remained potent with a high susceptibility rate by Sensititre BMD as follows: CZA against CRKP (95.0%), CREC (89.3%) and CRPA (84.5%); and CPT against MSSA (100.0%), MRSA (95.3%) and S. pneumoniae (94.3%). CZA was active against bla-carrying CRKP (98.5% susceptible), and resistance in the majority of CZA-resistant Enterobacterales isolates (6 of 10 CRKP and 2 of 3 CREC) was due to the presence of a metallo-β-lactamase gene.

Conclusion: Our results suggest that interpretation of susceptibility results obtained by Etest for both agents should be undertaken cautiously and remains challenging.
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http://dx.doi.org/10.1016/j.jgar.2021.06.016DOI Listing
July 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 Jul 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
July 2021

Clinical efficacy of antiviral agents against coronavirus disease 2019: A systematic review of randomized controlled trials.

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

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

Despite aggressive efforts on containment measures for the coronavirus disease 2019 (COVID-19) pandemic around the world, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously spreading. Therefore, there is an urgent need for an effective antiviral agent. To date, considerable research has been conducted to develop different approaches to COVID-19 therapy. In addition to early observational studies, which could be limited by study design, small sample size, non-randomized design, or different timings of treatment, an increasing number of randomized controlled trials (RCTs) investigating the clinical efficacy and safety of antiviral agents are being carried out. This study reviews the updated findings of RCTs regarding the clinical efficacy of eight antiviral agents against COVID-19, including remdesivir, lopinavir/ritonavir, favipiravir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, baloxavir, umifenovir, darunavir/cobicistat, and their combinations. Treatment with remdesivir could accelerate clinical improvement; however, it lacked additional survival benefits. Moreover, 5-day regimen of remdesivir might show adequate effectiveness in patients with mild to moderate COVID-19. Favipiravir was only marginally effective regarding clinical improvement and virological assessment based on the results of small RCTs. The present evidence suggests that sofosbuvir/daclatasvir may improve survival and clinical outcomes in patients with COVID-19. However, the sample sizes for analysis were relatively small, and all studies were exclusively conducted in Iran. Further larger RCTs in other countries are warranted to support these findings. In contrast, the present findings of limited RCTs did not indicate the use of lopinavir/ritonavir, sofosbuvir/ledipasvir, baloxavir, umifenovir, and darunavir/cobicistat in the treatment of patients hospitalized for COVID-19.
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http://dx.doi.org/10.1016/j.jmii.2021.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233451PMC
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

Scrub typhus and antibiotic-resistant .

Expert Rev Anti Infect Ther 2021 Jun 21:1-9. Epub 2021 Jun 21.

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

: Scrub typhus is one of the most underdiagnosed and under-reported febrile illnesses requiring hospitalization, mainly occurring in Southeast and East Asia and the Pacific Islands, in an area referred to as the 'Tsutsugamushi Triangle.' Scrub typhus is a zoonotic rickettsial disease that is transmitted to humans by trombiculid mites.: A MEDLINE/PubMed search of the available literature was performed to describe the role of antibiotic-resistant scrub typhus in therapy failure.: Scrub typhus is characterized by an eschar that may appear 2-3 days before sudden-onset fever with chills, headache, backache, myalgia, profuse sweating, vomiting, and enlarged lymph nodes. A macular or maculopapular skin rash can develop within 3-8 days after the onset of fever. Various antibiotics, such as chloramphenicol, tetracycline, doxycycline, macrolides, quinolones, and rifampicin, have been used to treat scrub typhus. Resistance to tetracycline has been proposed to underlie delayed clinical improvement since 1996, but recent reports have questioned the existence of doxycycline resistance. Nevertheless, the existence and importance of antibiotic-resistant scrub typhus remain uncertain and require further study.
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http://dx.doi.org/10.1080/14787210.2021.1941869DOI Listing
June 2021

Learning from the past: Taiwan's responses to COVID-19 versus SARS.

Int J Infect Dis 2021 Jun 5. Epub 2021 Jun 5.

Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address:

Objectives: To evaluate the prevalence of infection prevention behaviors in Taiwan-wearing facemasks and alcohol-based hand hygiene (AHH)-and compare their practice rates during SARS and COVID-19.

Methods: We surveyed 2328 Taiwanese from July 29 to August 6, 2020, assessing demographics, information sources, and preventive behaviors during the 2003 SARS outbreaks, 2009 pandemic influenza H1N1, COVID-19, and with post-survey intentions. Characteristics associated with the practice of preventive behaviors in 2020 were identified through logistic regression.

Results: Preventive behaviors were conscientiously practiced by 70.2% of participants. Compared with 2003 SARS/2009 H1N1, the percentages of facemask use (66.6% vs 99.2% [indoors], P < 0.001) and on-person AHH (44.2% vs 65.4% [hand sanitizers], P < 0.001) significantly increasedduring 2020 COVID-19. Highest adherence to preventive behaviors in 2020 was among females (adjusted odds ratio [aOR], 1.72), those receiving government COVID-19 information (aOR, 1.52), participants recruited from primary-care clinics (aOR, 1.43), and those who practiced AHH during 2003 SARS/2009 H1N1 (aOR, 1.37).

Conclusions: Government leadership, healthcare providers risk communication, and public cooperation rapidly mitigated the spread of COVID-19 in Taiwan even before vaccination. Future global efforts must implement such population-based preventive behaviors at a level above the viral-transmission-threshold, particularly in areas with fast-spreading SARS-CoV-2 variants.
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http://dx.doi.org/10.1016/j.ijid.2021.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178059PMC
June 2021

Seroprevalence Surveys for Anti-SARS-CoV-2 Antibody in Different Populations in Taiwan With Low Incidence of COVID-19 in 2020 and Severe Outbreaks of SARS in 2003.

Front Immunol 2021 18;12:626609. Epub 2021 May 18.

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

Accurate detection of anti-SARS-CoV-2 antibodies provides a more accurate estimation of incident cases, epidemic dynamics, and risk of community transmission. We conducted a cross-sectional seroprevalence study specifically targeting different populations to examine the performance of pandemic control in Taiwan: symptomatic patients with epidemiological risk and negative qRT-PCR test (Group P), frontline healthcare workers (Group H), healthy adult citizens (Group C), and participants with prior virologically-confirmed severe acute respiratory syndrome (SARS) infection in 2003 (Group S). The presence of anti-SARS-CoV-2 total and IgG antibodies in all participants were determined by Roche Elecsys Anti-SARS-CoV-2 test and Abbott SARS-CoV-2 IgG assay, respectively. Sera that showed positive results by the two chemiluminescent immunoassays were further tested by three anti-SARS-CoV-2 lateral flow immunoassays and line immunoassay (MIKROGEN Line SARS-CoV-2 IgG). Between June 29 and July 25, 2020, sera of 2,115 participates, including 499 Group P participants, 464 Group H participants, 1,142 Group C participants, and 10 Group S participants, were tested. After excluding six false-positive samples, SARS-CoV-2 seroprevalence were 0.4, 0, and 0% in Groups P, H, and C, respectively. Cross-reactivity with SARS-CoV-2 antibodies was observed in 80.0% of recovered SARS participants. Our study showed that rigorous exclusion of false-positive testing results is imperative for an accurate estimate of seroprevalence in countries with previous SARS outbreak and low COVID-19 prevalence. The overall SARS-CoV-2 seroprevalence was extremely low among populations of different exposure risk of contracting SARS-CoV-2 in Taiwan, supporting the importance of integrated countermeasures in containing the spread of SARS-CoV-2 before effective COVID-19 vaccines available.
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http://dx.doi.org/10.3389/fimmu.2021.626609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167053PMC
June 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

Species distribution and antifungal susceptibilities of clinical isolates of Penicillium and Talaromyces species in China.

Int J Antimicrob Agents 2021 Jul 24;58(1):106349. Epub 2021 Apr 24.

Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China; Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases (BZ0447), Beijing, China. Electronic address:

Morphologically identified Penicillium (n = 103) and Talaromyces marneffei (n = 8) isolates were collected from various clinical sources between 2016 and 2017 at a medical centre in Beijing, China. Identification to species level was confirmed by sequencing of the internal transcribed spacer (ITS) region, β-tubulin gene (benA) and RNA polymerase II second largest subunit (RPB2) gene. Of the 111 isolates, 56 (50.5%) were identified as Penicillium spp. and 55 (49.5%) as Talaromyces spp. Eleven species of Penicillium were detected, of which Penicillium oxalicum was the commonest, accounting for 51.8% (29/56), followed by Penicillium rubens (10.7%; 6/56) and Penicillium citrinum (10.7%; 6/56). Among the 55 Talaromyces isolates, nine species were identified, with Talaromyces funiculosus (36.4%; 20/55), Talaromyces stollii (27.3%; 15/55) and Talaromyces marneffei (14.5%; 8/55) being the most common. Of note, 89.3% (50/56) of the Penicillium isolates and 98.2% (54/55) of the Talaromyces isolates exhibited growth at 37°C. The isolates were mainly recovered from patients with pulmonary disorders (56.8%; 63/111), autoimmune disease (12.6%; 14/111) and AIDS (5.4%; 6/111). The azoles and amphotericin B exhibited potent activity against T. marneffei, while various levels of activity were observed against Penicillium and other Talaromyces species The echinocandins had the lowest MECs (MEC ≤0.12 mg/L) against most Penicillium and Talaromyces species, with the exception of T. marneffei whose MEC (4 mg/L) was five or more dilutions higher than that of the other species tested. These data on the species distribution and antifungal susceptibility expand the current clinical knowledge of Penicillium and Talaromyces species.
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http://dx.doi.org/10.1016/j.ijantimicag.2021.106349DOI Listing
July 2021

Potentially conjugative plasmids harboring Tn6636, a multidrug-resistant and composite mobile element, in Staphylococcus aureus.

J Microbiol Immunol Infect 2021 Mar 30. Epub 2021 Mar 30.

Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan UniversityCollege of Medicine, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address:

Objectives: This study aimed to provide detailed genetic characterization of Tn6636, a multidrug-resistant and composite mobile element, in clinical isolates of Staphylococcus aureus.

Methods: A total of 112 ermB-positive methicillin-susceptible S. aureus (MSSA) and 224 ermB-positive methicillin-resistant S. aureus (MRSA) isolates collected from 2000 to 2015 were tested for the presence of Tn6636. Detection of the plasmids harboring Tn6636 was performed by S1 nuclease digestion pulsed-field gel electrophoresis (PFGE) analysis, conjugation test, and whole genome sequencing (WGS).

Results: Prevalence of Tn6636 in MSSA is higher than that in MRSA. Ten MSSA isolates and 10 MRSA isolates carried Tn6636. The 10 MSSA isolates belonged to three sequence types (ST), including ST7 (n = 6), ST5 (n = 3), and ST59 (n = 1). The 10 MRSA isolates belonged to ST188 (n = 8) and ST965 (n = 2). Analysis of plasmid sequences revealed that Tn6636 was harbored by six different mosaic plasmids. In addition to resistance genes, some plasmids also harbored toxin genes.

Conclusion: The presence of multi-resistant Tn6636 in plasmids of both MSSA and MRSA with various STs suggests its broad dissemination. Results indicate that Tn6636 has existed for at least 16 years in Taiwan. The mosaic plasmids harboring Tn6636 can be transferred by conjugation. Ongoing surveillance of Tn6636 is essential to avoid continued spreading of resistant plasmids.
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http://dx.doi.org/10.1016/j.jmii.2021.03.003DOI Listing
March 2021

Species identification and antifungal susceptibility testing of Aspergillus strains isolated from patients with otomycosis in northern China.

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

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

Background/purpose: There are limited studies on species distribution and susceptibility profiles of Aspergillus strains isolated from patients with otomycosis in China.

Methods: A total of 69 confirmed Aspergillus species isolates were obtained from ear swabs of patients diagnosed with otomycosis from 2017 to 2018 in northern China. Identification of these Aspergillus isolates at the species level was performed using conventional morphological methods and MALDI-TOF MS in combination with molecular sequencing, and in vitro susceptibility to nine antifungal agents was evaluated using the Sensititre YeastOne system.

Results: The Aspergillus section Nigri had the greatest distribution of Aspergillus isolates. A. welwitschiae (n = 25) was the most predominant isolate in section Nigri, followed by A. tubingensis (n = 12) and A. niger (n = 11). Other Aspergillus species were also isolated, including A. terreus (n = 11), A. flavus/A. oryzae (n = 8), and A. fumigatus (n = 2). Amphotericin B, posaconazole, and echinocandins were highly in vitro active against all the isolates tested. 2.9% (2/69) of the isolates were resistant to azoles in our study, including one A. niger isolate with a high MIC value for itraconazole (ITR) (16 mg/L) and one A. tubingensis isolate cross-resistant to both voriconazole (VOR) (MIC >8 mg/L) and ITR (MIC >16 mg/L). One A. welwitschiae and one A. niger isolate both had increased MIC values of 4 mg/L against VOR.

Conclusions: A. welwitschiae was the most prevalent Aspergillus species isolated from patients with otomycosis. Our findings also indicated that the azole-resistant Aspergillus section Nigri should be utilized to guide clinical medication for Otomycosis.
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http://dx.doi.org/10.1016/j.jmii.2021.03.011DOI Listing
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

Clinical efficacy and safety of remdesivir in patients with COVID-19: a systematic review and network meta-analysis of randomized controlled trials.

J Antimicrob Chemother 2021 07;76(8):1962-1968

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

Objectives: We performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) to provide updated information regarding the clinical efficacy of remdesivir in treating coronavirus disease 2019 (COVID-19).

Methods: PubMed, Embase, Cochrane Library, clinical trial registries of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched for relevant articles published up to 18 November 2020.

Results: Five RCTs, including 13 544 patients, were included in this meta-analysis. Among them, 3839 and 391 patients were assigned to the 10 day and 5 day remdesivir regimens, respectively. Patients receiving 5 day remdesivir therapy presented greater clinical improvement than those in the control group [OR = 1.68 (95% CI 1.18-2.40)], with no significant difference observed between the 10 day and placebo groups [OR = 1.23 (95% CI 0.90-1.68)]. Patients receiving remdesivir revealed a greater likelihood of discharge [10 day remdesivir versus control: OR = 1.32 (95% CI 1.09-1.60); 5 day remdesivir versus control: OR = 1.73 (95% CI 1.28-2.35)] and recovery [10 day remdesivir versus control: OR = 1.29 (95% CI 1.03-1.60); 5 day remdesivir versus control: OR = 1.80 (95% CI 1.31-2.48)] than those in the control group. In contrast, no mortality benefit was observed following remdesivir therapy. Furthermore, no significant association was observed between remdesivir treatment and an increased risk of adverse events.

Conclusions: Remdesivir can help improve the clinical outcome of hospitalized patients with COVID-19 and a 5 day regimen, instead of a 10 day regimen, may be sufficient for treatment. Moreover, remdesivir appears as tolerable as other comparators or placebo.
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http://dx.doi.org/10.1093/jac/dkab093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083728PMC
July 2021

Increased antimicrobial resistance during the COVID-19 pandemic.

Int J Antimicrob Agents 2021 Apr 19;57(4):106324. Epub 2021 Mar 19.

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

In addition to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection itself, an increase in the incidence of antimicrobial resistance poses collateral damage to the current status of the COVID-19 (coronavirus disease 2019) pandemic. There has been a rapid increase in multidrug-resistant organisms (MDROs), including extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae, carbapenem-resistant New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales, Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), pan-echinocandin-resistant Candida glabrata and multi-triazole-resistant Aspergillus fumigatus. The cause is multifactorial and is particularly related to high rates of antimicrobial agent utilisation in COVID-19 patients with a relatively low rate of co- or secondary infection. Appropriate prescription and optimised use of antimicrobials according to the principles of antimicrobial stewardship as well as quality diagnosis and aggressive infection control measures may help prevent the occurrence of MDROs during this pandemic.
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http://dx.doi.org/10.1016/j.ijantimicag.2021.106324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972869PMC
April 2021

Clostridioides difficile infection in patients with hematological malignancy: A multicenter study in Taiwan.

J Microbiol Immunol Infect 2021 Feb 20. Epub 2021 Feb 20.

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: Among the individuals with hematological malignancy (HM) complicated with Clostridioides difficile infection (CDI), the variables associated with in-hospital mortality and recurrence of CDI were investigated.

Material And Methods: Including adults with HM and those without malignancy suffering from CDI from January 2015 to December 2016 in three hospitals in Taiwan.

Results: Totally 314 patients including 77 with HM and 237 patients without malignancy were included. HM patients more often had low leukocyte counts (<500 cells/mL: 28.6% vs. 2.1%) than those without malignancy and more patients without malignancy had severe CDI than patients with HM (31.6% vs. 14.3%, P = .003), according to the severity score of IDSA/SHEA. Patients with HM had a higher recurrence rate of CDI (14.3%, 11/77 vs. 7.2%, 17/237; P = .07) and longer hospital stay (47.2 ± 40.8 days vs. 33.3 ± 37.3 days; P = .006) than those without malignancy. In the multivariate analyses for those with HM and CDI, the in-hospital mortality was associated with vancomycin-resistant Enterococcus (VRE) colonization or infection (odds ratio [OR] 7.72; P = .01), and C. difficile ribotype 078 complex infection (OR 9.22; P = .03). Moreover underlying hematological malignancy (OR 2.74; P = .04) and VRE colonization/infection (OR 2.71; P = .02) were independently associated with CDI recurrence.

Conclusion: Patients with HM complicated with CDI were often regarded as non-severe infection, but had a similar in-hospital mortality rate as those without malignancy. CDI due to ribotype 078 complex isolates heralded a poor prognosis among HM patients.
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http://dx.doi.org/10.1016/j.jmii.2021.02.002DOI Listing
February 2021

Multicenter evaluation of four immunoassays for the performance of early diagnosis of COVID-19 and assessment of antibody responses of patients with pneumonia in Taiwan.

J Microbiol Immunol Infect 2021 Feb 23. Epub 2021 Feb 23.

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

Background/purpose: Our study goals were to evaluate the diagnostic performance of four anti-SARS-CoV-2 antibodies tests and the differences in dynamic immune responses between COVID-19 patients with and without pneumonia.

Methods: We collected 184 serum samples from 70 consecutively qRT-PCR-confirmed COVID-19 patients at four participating hospitals from 23 January 2020 to 30 September 2020. COVID-19 pneumonia was defined as the presence of new pulmonary infiltration. Serum samples were grouped by the duration after symptom onset on a weekly basis for antibody testing and analysis. The four immunoassays: Beckman SARS-CoV-2 IgG/IgM (Beckman Test), Siemens (ADVIA Centaur®) SARS-CoV-2 Total (COV2T) (Siemens Test), SBC COVID-19 IgG ELISA (SBC Test) and EliA SARS-CoV-2-Sp1 IgG/IgM/IgA P2 Research (EliA Test) were used for detecting the SARS-CoV-2 specific antibodies.

Results: The sensitivity of all tests reached 100% after 42 days of symptom onset. Siemens Test, the only test detecting total anti-SARS-CoV-2 antibodies, had the best performance in the early diagnosis of COVID-19 infection (day 0-7: 77%; day 8-14: 95%) compared to the other 3 serological tests. All tests showed 100% specificity except SBC Test (98%). COVID-19 patients with pneumonia had significantly higher testing signal values than patients without pneumonia (all p values < 0.05, except EliA IgM Test). However, Siemens Test and SBC Test had highest probability in early prediction of the presence of COVID-19 pneumonia.

Conclusion: Chronological analysis of immune response among COVID-19 patients with different serological tests provides important information in the early diagnosis of SARS-CoV-2 infection and prediction of the risk of pneumonia after infection.
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http://dx.doi.org/10.1016/j.jmii.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900773PMC
February 2021

The impact of the coronavirus disease 2019 epidemic on notifiable infectious diseases in Taiwan: A database analysis.

Travel Med Infect Dis 2021 Mar-Apr;40:101997. Epub 2021 Feb 25.

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

Introduction: The impact of the COVID-19 pandemic on the incidence of notifiable infectious diseases (NIDs) in Taiwan remains unclear.

Materials And Methods: The number of cases of NID (n = 42) between January and September 2019 and 2020 were obtained from the open database from Taiwan Centers for Disease Control.

Results: The number of NID cases was 21,895 between January and September 2020, which was lower than the number of cases during the same period in 2019 (n = 24,469), with a decline in incidence from 102.9 to 91.7 per 100,000 people in 2019 and 2020, respectively. Fourteen airborne/droplet, 11 fecal-oral, seven vector-borne, and four direct-contact transmitted NID had an overall reduction of 2700 (-28.1%), 156 (-23.0%), 557 (-54.8%), and 73 (-45.9%) cases, respectively, from 2019 to 2020. Similar trends were observed for the changes in incidence, which were 11.5 (-28.4%), 6.7 (-23.4%), 2.4 (-55.0%), and 0.3 (-46.2%) per 100,000 people for airborne/droplet, fecal-oral, vector-borne, and direct-contact transmitted NID, respectively. In addition, all the 38 imported NID showed a reduction of 632 (-73.5%) cases from 2019 to 2020. In contrast, 4 sexually transmitted diseases (STDs) showed an increase of 903 (+7.2%) cases from 2019 to 2020, which was attributed to the increase in gonorrhea (from 3220 to 5028). The overall incidence of STDs increased from 52.5 to 56.0 per 100,000 people, with a percentage change of +6.7%.

Conclusion: This study demonstrated a collateral benefit of COVID-19 prevention measures for various infectious diseases, except STDs, in Taiwan, during the COVID-19 epidemic.
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http://dx.doi.org/10.1016/j.tmaid.2021.101997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905388PMC
April 2021

How to Keep COVID-19 at Bay: A Taiwanese Perspective.

J Epidemiol Glob Health 2021 03 4;11(1):1-5. Epub 2020 Nov 4.

Departments of Laboratory Medicine and Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.

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http://dx.doi.org/10.2991/jegh.k.201028.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958278PMC
March 2021

Antimicrobial stewardship capacity and manpower needs in the Asia Pacific.

J Glob Antimicrob Resist 2021 03 3;24:387-394. Epub 2021 Feb 3.

Asia Pacific Foundation for Infectious Diseases, Seoul, Republic of Korea; CHA Bio Group, Gyeonggi-do, Republic of Korea.

Objectives: Antimicrobial stewardship is a strategy to combat antimicrobial resistance in hospitals. Given the burden and impact of antimicrobial resistance in the Asia Pacific, it is important to document capacity and gaps in antimicrobial stewardship programmes (ASP). We aimed to understand existing capacities and practices, and define the resources needed to establish antimicrobial stewardship where it is lacking.

Methods: An anonymous online survey, consisting of questions on antimicrobial control at country, hospital and programme levels, was circulated to healthcare providers in the field of infectious diseases and microbiology through Asian Network for Surveillance of Resistant Pathogens, ReAct Group and the Australasian Society for infectious Diseases.

Results: 139 participants from 16 countries or regions completed the survey. The majority of participants were adult infectious diseases physicians (61/139, 43.9%) and microbiologists (31/139, 22.3%). Participants from 7 countries reported that antimicrobials can be obtained without prescriptions. Despite the high percentage (75.5%) of respondents working in large hospitals, only 22/139 participants (15.8%) from Australia, China, Singapore, Taiwan, Thailand and Vietnam reported having more than 10 infectious diseases physicians. Hospital empiric antimicrobial guidelines for common infections were available according to 110/139 (79.1%) participants. Pre-authorisation of antimicrobials was reported by 88/113 (77.9%) respondents while prospective audit and feedback was reported by 93/114 (81.6%). Automatic stop orders and culture-guided de-escalation were reported by only 52/113 (46.0%) and 27/112 (24.1%) respectively.

Conclusion: The survey reveals a wide range of ASP development in Asia Pacific. Establishing national workgroups and guidelines will help advance antimicrobial stewardship in this diverse region.
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http://dx.doi.org/10.1016/j.jgar.2021.01.013DOI Listing
March 2021

Longitudinal non-cystic fibrosis trends of pulmonary disease from 2010 to 2017: spread of the "globally successful clone" in Asia.

ERJ Open Res 2021 Jan 18;7(1). Epub 2021 Jan 18.

Dept of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Background: (MAB) has emerged as the predominant pulmonary non-tuberculous mycobacterial pathogen in parts of Asia, including Taiwan. The reasons for the significant increase in MAB infections in the non-cystic fibrosis (CF) populations are poorly understood. The study aimed to elucidate whether this increase is related to the spread of the globally successful clone of MAB.

Methods: We performed multilocus sequence typing of 371 nonduplicated MAB pulmonary isolates from 371 patients sampled between 2010-2017 at seven hospitals across Taiwan.

Results: In total, 183 (49.3%) isolates were subsp. (MAB-a), 187 (50.4%) were subsp. (MAB-m), and 1 (0.3%) was subsp. (MAB-b). MAB-a sequence type (ST)1 (23.7%) and ST127 (3.8%), followed by MAB-m ST48 (16.2%), ST117 (15.1%), ST23 (8.6%) were most common overall. Of MAB-a strains, 50 (27.3%) belonged to novel STs and 38 (10.2%) were singleton strains, while of MAB-m strains, only 10 (5.3%) were novel and 8 (2.2%) were singletons. From 2010 to 2017, the frequency of the historically dominant ST1 declined from 28.6% to 22.5%, whereas the recently emerged globally successful clonal cluster 3, ST23 and ST48, increased from 14.3% to 40.0%.

Conclusions: The dominance of ST1 particularly in the last 2 years of this study appears to be declining, while ST23, reported in outbreaks among CF and post-surgical cohorts across the Americas and Europe, alongside the closely related ST48, is present among non-CF populations in Taiwan. These trends need to be confirmed with further ongoing studies to track the molecular epidemiology of clinical MAB isolates worldwide.
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http://dx.doi.org/10.1183/23120541.00191-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836708PMC
January 2021
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