Publications by authors named "Wen-Liang Yu"

97 Publications

Appropriate use of antimicrobial therapy for COVID-19 co-infection.

Immunotherapy 2021 Jun 11. Epub 2021 Jun 11.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan.

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http://dx.doi.org/10.2217/imt-2021-0134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202506PMC
June 2021

Klebsiella pneumoniae Harboring Carbapenemase Genes in Taiwan: Its Evolution over 20 Years, 1998-2019.

Int J Antimicrob Agents 2021 May 6:106354. Epub 2021 May 6.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Klebsiella pneumoniae (K. pneumoniae) is an important pathogen causing various types of human infections in Taiwan. Carbapenemases have increasingly been reported in Enterobacterales in the past two decades. Carbapenemase-producing K. pneumoniae (CPKP), a major resistance concern that has emerged during the last decade, has become a global threat, with its related infections associated with high morbidity and mortality; however, therapeutic options for CPKP-associated infections are limited. Carbapenemases - including K. pneumoniae carbapenemases (KPC)-2, New Delhi metallo-β-lactamase (NDM)-1, Verona integron-encoded metallo-β-lactamase (VIM)-1, imipenemase (IMP)-1, and oxacillinase (OXA)-48 - have been reported worldwide, with a marked prevalence in different countries or areas of the world. Understanding the epidemiology of carbapenemase producers is important for the prevention of their expansion. This review examined the evolution of CPKP in the last two decades to better understand the role of CPKP in Taiwan. It discovered that the endemicity has changed from IMP-8, NDM-1 and VIM-1 to the most common KPC-2 and rapidly emerging OXA-48. Resistance epidemiology, genetic background, virulence factors, therapy, and outcomes are discussed in this paper.
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http://dx.doi.org/10.1016/j.ijantimicag.2021.106354DOI Listing
May 2021

Epidemiological Correlation of Pulmonary Infections with Ambient Pollutions and Influenza A (H1N1) in Southern Taiwan.

J Fungi (Basel) 2021 Mar 19;7(3). Epub 2021 Mar 19.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan.

An increase in fungal spores in ambient air is reported during a spike in particulate matter (PM and PM) aerosols generated during dust or smog events. However, little is known about the impact of ambient bioaerosols on fungal infections in humans. To identify the correlation between the incidence of pulmonary aspergillosis and PM-associated bioaerosols (PM and PM), we retrospectively analyzed data between 2015 and 2018 (first stage) and prospectively analyzed data in 2019 (second stage). Patient data were collected from patients in three medical institutions in Tainan, a city with a population of 1.88 million, located in southern Taiwan. PM data were obtained from the Taiwan Air Quality Monitoring Network. Overall, 544 non-repeated aspergillosis patients (first stage, = 340; second stage, = 204) were identified and enrolled for analysis. The trend of aspergillosis significantly increased from 2015 to 2019. Influenza A (H1N1) and ambient PMs (PM and PM) levels had significant effects on aspergillosis from 2015 to 2018. However, ambient PMs and influenza A (H1N1) in Tainan were correlated with the occurrence of aspergillosis in 2018 and 2019, respectively. Overall (2015-2019), aspergillosis was significantly correlated with influenza ( = 0.002), influenza A (H1N1) ( < 0.001), and PM ( = 0.040) in Tainan City. Using a stepwise regression model, influenza A (H1N1) ( < 0.0001) and Tainan PM ( = 0.016) could significantly predict the occurrence of aspergillosis in Tainan. PM-related bioaerosols and influenza A (H1N1) contribute to the incidence of pulmonary aspergillosis.
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http://dx.doi.org/10.3390/jof7030227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003483PMC
March 2021

Cardiovascular Complications of COVID-19 and Associated Concerns: A Review.

Acta Cardiol Sin 2021 Jan;37(1):9-17

Institute of Clinical Medicine, College of Medicine, National Cheng Kung University.

SARS-CoV-2 is the virus that has caused the current coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 is characterized by significantly affecting the cardiovascular system of infected patients. In addition to the direct injuries caused by the virus, the subsequent cytokine storm - an overproduction of immune cells and their activating compounds - also causes damage to the heart. The development of anti-SARS-CoV-2 treatments is necessary to control the epidemic. Despite an explosive growth in research, a comprehensive review of up-to-date information is lacking. Herein, we summarize pivotal findings regarding the epidemiology, complications, and mechanisms of, and recent therapies for, COVID-19, with special focus on its cardiovascular impacts.
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http://dx.doi.org/10.6515/ACS.202101_37(1).20200913ADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814323PMC
January 2021

Cefoperazone/sulbactam: New composites against multiresistant gram negative bacteria?

Infect Genet Evol 2021 Mar 5;88:104707. Epub 2021 Jan 5.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Sulbactam, a class A β-lactamase inhibitor, added to cefoperazone either at a fixed 8 mg/L level of sulbactam or at a level of fixed cefoperazone: sulbactam ratio (2:1) would constitute a combination form of cefoperazone/sulbactam, which has better activities against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii than cefoperazone alone. Cefoperazone/sulbactam (1:1 or 1:2) has greater in-vitro activity against most multidrug-resistant organisms (ESBL- and AmpC-producing Enterobacteriaceae and carbapenem-resistant A. baumannii except for carbapenem-resistant P. aeruginosa) than a 2:1 ratio. However, increased sulbactam concentration may induce AmpC production. Besides, sulbactam concentration might not be readily achievable in serum if the susceptibility rates were defined by the breakpoints of higher sulbactam composites, such as ≤16/16 (1:1) or 16/32 (1:2) mg/L. Carbapenemases (KPC-, OXA-type enzymes and metallo-β-lactamases) can't be inhibited by sulbactam. Some in-vitro studies showed that increasing sulbactam composites of cefoperazone/sulbactam had no effect on carbapenem-resistant P. aeruginosa, suggesting the presence of carbapenemases or AmpC overproduction that could not be overcome by increasing sulbactam levels to recover cefoperazone activity. Sulbactam alone has good intrinsic activity against carbapenem-resistant Acinetobacter strains sometimes even in the presence of carbapenemase genes, suggesting unsteady levels of carbapenemases. In conclusion, appropriate composites of cefoperazone and β-lactamase inhibitor sulbactam may expand the clinical use if the pharmacokinetic optimization could be achieved in the human serum.
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http://dx.doi.org/10.1016/j.meegid.2021.104707DOI Listing
March 2021

Management of acute cardiovascular events in patients with COVID-19.

Rev Cardiovasc Med 2020 12;21(4):577-581

Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, 70101, Tainan, Taiwan.

The pandemic of coronavirus disease 2019 (COVID-19) caused by the newly discovered virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had been noticed to have high morbidity and mortality. Apart from pneumonia, COVID-19 can also cause damage to the cardiovascular system, and co-occurring with cardiovascular injury leads to a poorer prognosis. Besides, amid the pandemic of COVID-19, the management of critical cardiovascular events needs to further account for the highly infectious coronavirus, prompt and optimal treatments, clinician's safety, and healthcare provider's capacity. This review article aims to provide more comprehensive and appropriate guidance for the management of critical cardiovascular disease, including ST-segment elevation myocardial infarction (STEMI), non-STEMI acute coronary syndrome, cardiogenic shock, acute heart failure, cardiopulmonary resuscitation, and advanced care planning, during the COVID-19 epidemic.
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http://dx.doi.org/10.31083/j.rcm.2020.04.140DOI Listing
December 2020

A mysterious surge of aspergillosis among non-SARS-CoV-2 patients during COVID-19 pandemic.

J Microbiol Immunol Infect 2021 Feb 1;54(1):156-158. Epub 2020 Dec 1.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jmii.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706424PMC
February 2021

Cardiac Involvement of COVID-19: A Comprehensive Review.

Am J Med Sci 2021 01 6;361(1):14-22. Epub 2020 Oct 6.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2 caused COVID-19 has reached a pandemic level. COVID-19 can significantly affect patients' cardiovascular systems. First, those with COVID-19 and preexisting cardiovascular disease have an increased risk of severe disease and death. Mortality from COVID-19 is strongly associated with cardiovascular disease, diabetes, and hypertension. Second, therapies under investigation for COVID-19 may have cardiovascular side effects of arrhythmia. Third, COVID-19 is associated with multiple direct and indirect cardiovascular complications. Associated with a high inflammatory burden related to cytokine release, COVID-19 can induce vascular inflammation, acute myocardial injury, myocarditis, arrhythmias, venous thromboembolism, metabolic syndrome and Kawasaki disease. Understanding the effects of COVID-19 on the cardiovascular system is essential for providing comprehensive medical care for cardiac and/or COVID-19 patients. We hereby review the literature on COVID-19 regarding cardiovascular virus involvement.
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http://dx.doi.org/10.1016/j.amjms.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536131PMC
January 2021

Collateral benefits on other respiratory infections during fighting COVID-19.

Med Clin (Engl Ed) 2020 Sep 30;155(6):249-253. Epub 2020 Sep 30.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan.

Purpose: Influenza virus infection is associated with a high disease burden. COVID-19 caused by SARS-CoV-2 has become a pandemic outbreak since January 2020. Taiwan has effectively contained COVID-19 community transmission. We aimed to validate whether fighting COVID-19 could help to control other respiratory infections in Taiwan.

Method: We collected week-case data of severe influenza, invasive disease and death toll from pneumonia among 25 calendar weeks of the influenza season for four years (2016-2020), which were reported to Taiwan CDC. Trend and slope differences between years were compared.

Result: A downturn trend of severe influenza, invasive disease and the death toll from pneumonia per week in 2019/2020 season and significant trend difference in comparison to previous seasons were noted, especially after initiation of several disease prevention measures to fight potential COVID-19 outbreak in Taiwan.

Conclusions: Fighting COVID-19 achieved collateral benefits on significant reductions of severe influenza burden, invasive disease activity, and the death toll from pneumonia reported to CDC in Taiwan.
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http://dx.doi.org/10.1016/j.medcle.2020.05.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526628PMC
September 2020

Collateral benefits on other respiratory infections during fighting COVID-19.

Med Clin (Barc) 2020 09 5;155(6):249-253. Epub 2020 Jun 5.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Purpose: Influenza virus infection is associated with a high disease burden. COVID-19 caused by SARS-CoV-2 has become a pandemic outbreak since January 2020. Taiwan has effectively contained COVID-19 community transmission. We aimed to validate whether fighting COVID-19 could help to control other respiratory infections in Taiwan.

Method: We collected week-case data of severe influenza, invasive Streptococcus pneumoniae disease and death toll from pneumonia among 25 calendar weeks of the influenza season for four years (2016-2020), which were reported to Taiwan CDC. Trend and slope differences between years were compared.

Result: A downturn trend of severe influenza, invasive S. pneumoniae disease and the death toll from pneumonia per week in 2019/2020 season and significant trend difference in comparison to previous seasons were noted, especially after initiation of several disease prevention measures to fight potential COVID-19 outbreak in Taiwan.

Conclusions: Fighting COVID-19 achieved collateral benefits on significant reductions of severe influenza burden, invasive S. pneumoniae disease activity, and the death toll from pneumonia reported to CDC in Taiwan.
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http://dx.doi.org/10.1016/j.medcli.2020.05.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274613PMC
September 2020

A Double-Edged Sword-Cardiovascular Concerns of Potential Anti-COVID-19 Drugs.

Cardiovasc Drugs Ther 2021 Apr 17;35(2):205-214. Epub 2020 Jun 17.

Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). COVID-19 significantly affects multiple systems including the cardiovascular system. Most importantly, in addition to the direct injury from the virus per se, the subsequent cytokine storm, an overproduction of immune cells and their activating compounds, causes devastating damage. To date, emerging anti-SARS-CoV-2 treatments are warranted to control epidemics. Several candidate drugs have been screened and are currently under investigation. These primarily include antiviral regimens and immunomodulatory regimens. However, beyond the anti-SARS-CoV-2 effects, these drugs may also have risks to the cardiovascular system, especially altering cardiac conduction. Herein, we review the cardiovascular risks of potential anti-COVID-19 drugs.
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http://dx.doi.org/10.1007/s10557-020-07024-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297930PMC
April 2021

Tigecycline Therapy for Infections Caused by Extended-Spectrum β-Lactamase-Producing in Critically Ill Patients.

Antibiotics (Basel) 2020 May 5;9(5). Epub 2020 May 5.

Department of Medical Research, Chi Mei Medical Center, Tainan 710, Taiwan.

We aimed to evaluate tigecycline on the clinical effectiveness in treating complicated skin and soft tissue infections (cSSTI), complicated intra-abdominal infections (cIAI), and pneumonia, caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, as data are limited. From three medical centers in Taiwan, we retrospectively studied the cSSTI, cIAI, and/or pneumonia caused by ESBL-producing Enterobacteriaceae. Among the 71 patients, including 39 patients infected with , 30 infected with and others, the clinical success rate of tigecycline-based therapy was 80%-90% for pneumonia and cSSTI caused by and 50%-60% for cIAI caused by and . Microbiological and clinical outcome of pneumonia caused by carbapenem-resistant was poor. Univariate Cox analysis showed that dyspnea, SOFA score, septic shock, thrombocytopenia, prolonged prothrombin time, and lesser microbiological eradication were significant factors associated with 30-day mortality after the end of therapy. Cox regression proportional hazards model revealed dyspnea and a SOFA score > 8 to be independently associated with time to death. For ESBL producers, tigecycline showed good effects for cSSTI and pneumonia by , ordinary for cIAI, but ineffective for pneumonia by . Dyspnea and a high SOFA score predict a poor outcome.
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http://dx.doi.org/10.3390/antibiotics9050231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277187PMC
May 2020

Dynamic Variation in Occurrence of Influenza A(H1N1)-Associated Invasive Pulmonary Aspergillosis in Southern Taiwan.

Clin Infect Dis 2021 03;72(5):899-900

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan.

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http://dx.doi.org/10.1093/cid/ciaa404DOI Listing
March 2021

Aspergillosis related to severe influenza: A worldwide phenomenon?

Clin Respir J 2019 Aug 26;13(8):540-542. Epub 2019 May 26.

Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.

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http://dx.doi.org/10.1111/crj.13036DOI Listing
August 2019

Chimeric Antigen Receptor T-cell (CAR T) Therapy for Hematologic and Solid Malignancies: Efficacy and Safety-A Systematic Review with Meta-Analysis.

Cancers (Basel) 2019 Jan 7;11(1). Epub 2019 Jan 7.

Jiangsu Target Pharma Laboratories Inc., Changzhou High-Tech Research Institute of Nanjing University, Changzhou 213164, China.

Chimeric antigen receptors T cells (CAR T) had been used for treating various tumor patients in clinic, and owned an incredible efficacy in part of malignancies. However, CAR T therapy remains controversial due to doubts about its efficacy and safety in the clinical treatment of various malignancies. A total of 997 tumor patients from 52 studies were included in this review. Eligible studies were searched and reviewed from the databases of PubMed, Web of Science, Wanfang and Clinicaltrials.gov. Then meta-analysis and subgroup analysis were used to investigate the overall response rate (ORR), complete response rate (CRR), common side effect rate (CSER) and relapse rate (RR) of CAR T therapy for patients in clinical researches, respectively. The results further confirmed that CAR T therapy had a higher response rate for hematologic malignancies. More importantly, CAR T therapy had a higher CSER in patients with hematologic malignancies, and it had a similar RR in patients with different malignancies. Cell cultured without the addition of IL-2 and total administration less than 10⁸ cells were recommended. This study offers a reference for future research regarding the application in solid and hematologic malignancies, side effects and relapse, and even the production processes of CAR T cells.
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http://dx.doi.org/10.3390/cancers11010047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356949PMC
January 2019

Detection of Plasmid-Mediated β-Lactamase Genes and Emergence of a Novel AmpC (CMH-1) in at a Medical Center in Southern Taiwan.

J Clin Med 2018 Dec 20;8(1). Epub 2018 Dec 20.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan 710, Taiwan.

The plasmid-mediated extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases in spp. have increasingly been reported. In this study, we investigated the prevalence of the plasmid-mediated β-lactamases in from bloodstream isolates at a medical center in southern Taiwan. ESBL and genes were detected by PCRs and DNA sequencing. Conjugation experiments were conducted to confirm the transferability of the genetic resistance trait. Among 41 non-repetitive blood isolates of cefuroxime-resistant , eight isolates exhibited ESBL phenotype confirmed by double-disk synergistic tests. Nearly all the strains were susceptible to carbapenems. The prevalence rate of the plasmid-mediated genes was 73% (30/41), including one , one , two novel genes and other genes. Coexistence of plasmid-mediated and ESBL genes (10 with and one with ) was observed. Successful transmissions of the and were demonstrated in some transconjugants. The inducible or derepressed CMH-1 had expanded activity of isolates versus ceftazidime. Enterobacterial repetitive intergenic consensus (ERIC)-PCR analysis and pulsotype showed distinct patterns suggesting non-clonal relationship. In conclusion, plasmid-mediated genes in isolates have been highly prevalent in southern Taiwan and may continue genetic evolution, contributing to the complexities in antibiotic-resistant mechanisms.
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http://dx.doi.org/10.3390/jcm8010008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352282PMC
December 2018

Evaluation of effectiveness of granulocyte-macrophage colony-stimulating factor therapy to cancer patients after chemotherapy: a meta-analysis.

Oncotarget 2018 Jun 15;9(46):28226-28239. Epub 2018 Jun 15.

The State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macao, China.

The impact of granulocyte-macrophage colony stimulating factor (GM-CSF) on hematologic indexes and complications remains existing contradictory evidence in cancer patients after treatment of chemotherapy. Eligible studies up to March 2017 were searched and reviewed from PubMed and Wanfang databases. Totally 1043 cancer patients from 15 studies were included in our research. The result indicated that GM-CSF could significantly improve white blood cells count (SMD = 1.16, 95% CI: 0.71 - 1.61, Z = 5.03, < 0.00001) and reduce the time to leukopenia recovery (SMD = -0.85, 95% CI: -1.16 - -0.54, Z = 5.38, < 0.00001) in cancer patients after treatment of chemotherapy. It also could improve absolute neutrophil count (SMD = 1.11, 95% CI: 0.39 - 1.82, Z = 3.04, = 0.002) and significantly shorten the time to neutropenia recovery (SMD = -1.47, 95% CI: -2.20 - -1.75, Z = 3.99, < 0.0001). However, GM-CSF could not improve blood platelet (SMD = 0.46, 95% CI: -0.37 - -1.29, Z = 1.10, = 0.27). And GM-CSF had significant connection with fever (RR = 3.44, 95% CI: 1.43 - 8.28, Z = 2.76, = 0.006). The publication bias existed in the data of the impact of GM-CSF on blood platelet and complication. In conclusions, GM-CSF had an intimate association with some hematologic indexes and complications. Our study suggested that more hematological indexes and even more other indexes need to be observed in future studies.
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http://dx.doi.org/10.18632/oncotarget.24890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021338PMC
June 2018

Purulent constrictive pericarditis caused by Salmonella enteritidis in a patient with adult-onset Still's disease: A case report.

Medicine (Baltimore) 2017 Dec;96(50):e8949

Division of Cardiovascular Surgery, Department of Surgery Department of Intensive Care Unit, Chi Mei Medical Center Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University Department of Medical Education, Taipei Veteran General Hospital School of Medicine, National Defense Medical Center Department of Hospital and Health Care Administration, Biotechnology, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.

Rationale: Purulent pericarditis is a rare and usually fatal disease. Immunodeficiency state and preexisting pericardial effusion can predispose patients to infections. However, we are not aware of similar cases in patients with adult-onset Still's disease (AOSD). In addition, it is seldom caused by Salmonella bacteria.

Patient Concerns: We report a 30-year-old woman with dyspnea on exertion and epigastric fullness. She was newly diagnosed with AOSD 4 months previously and medicated with prednisolone.

Diagnoses: Transthoracic echocardiography (TTE) and computed tomography revealed a thickened pericardium with loculations in the pericardial space, consistent with purulent constrictive pericarditis. Subsequent cultures of blood and pericardial fluid yielded S enteritidis.

Interventions: She underwent subtotal pericardiectomy through a limited median sternotomy, and antibiotic therapy (ceftriaxone) for 1 month.

Outcomes: The New York Heart Association functional classification downgraded from class III to class I. There was no recurrence during the 1-year follow-up.

Lessons: This case presents an opportunity to highlight the importance of considering purulent pericarditis in patients previously diagnosed with AOSD. High clinical suspicion, early diagnosis, and prompt management can result in a better outcome in purulent pericarditis.
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http://dx.doi.org/10.1097/MD.0000000000008949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815698PMC
December 2017

Klebsiella pneumoniae Isolates from Meningitis: Epidemiology, Virulence and Antibiotic Resistance.

Sci Rep 2017 07 26;7(1):6634. Epub 2017 Jul 26.

Department of Intensive Care Medicine, Chi-Mei Medical Center, Tainan, Taiwan.

Klebsiella pneumoniae (KP) resistance to broad-spectrum cephalosporin (BSC) in meningitis is important because of limited therapeutic options. To investigate the antibiotic resistance, virulence and epidemiology of KP in meningitis, we conducted a retrospective study for 33 non-metastatic isolates, including primary meningitis (n = 20) and post-craniotomy meningitis (n = 13) collected from 1999 to 2013. BSC resistance was found in 9 (27.3%) isolates, all from post-craniotomy meningitis, harboring bla (n = 6), bla (n = 2), bla (n = 2), and bla (n = 1). Positive virulence factors were hypermucoviscosity (n = 22), larger bacterial size (n = 24), virulent capsule serotypes (n = 24, K2, 11; K1, 5; K57, 3; K5, 2; K20, 2 and K54, 1), rmpA (n = 23), rmpA (n = 20), aerobactin gene (n = 22) and high-grade serum resistance (n = 23, 69.7%). Higher mouse lethality (LD < 10) was found in 16 isolates (48.5%). Post-craniotomy isolates were significantly less virulent than primary meningitis isolates, except for similar serum resistance capability. The pulsotype and sequence typing (ST) results were diverse. A minor cluster with pulsotype C and ST23 (n = 5) was identified in primary meningitis isolates. In conclusion, virulence factors and BSC resistance corresponded to about 70% and 30% of KP meningitis isolates respectively. BSC remains appropriate for treating primary meningitis, whereas meropenem is indicated for post-craniotomy meningitis empirically.
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http://dx.doi.org/10.1038/s41598-017-06878-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529541PMC
July 2017

Comparison of synergism between colistin, fosfomycin and tigecycline against extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolates or with carbapenem resistance.

J Microbiol Immunol Infect 2017 Dec 6;50(6):931-939. Epub 2017 Jul 6.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan City, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan. Electronic address:

Purpose: To investigate the synergistic and bactericidal effects of antimicrobial combinations of any two of colistin, fosfomycin and tigecycline against the nine extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (KP) clinical isolates, including 4 carbapenem-susceptible strains and five imipenem and/or meropenem-resistant strains.

Methods: In vitro synergism and bactericidal activity of combination of colistin, fosfomycin and tigecycline were evaluated by time-kill studies in standard inoculum of bacterial densities of a suspension containing 5 × 10 CFU/mL by using 1/2× MIC for each alone, and both 1/2× and 1/4× MIC for any two drugs. The settings of low MIC dosing were allowed to rapidly survey the most active drug combination.

Results: The most active combination group was colistin plus tigecycline, showing synergy in 8 isolates and bactericidal activities in 6 isolates by using concentrations of 1/2× MIC and 1/4× MIC, respectively. The least active combination was tigecycline plus fosfomycin, which showed synergy in only 4 isolates and no bactericidal activities by using concentrations of 1/2× MIC and 1/4× MIC, respectively.

Conclusions: The combination of tigecycline and colistin may be considered as a last-resort approach to the ESBL-producing KP infections, especially those isolates with carbapenem resistance.
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http://dx.doi.org/10.1016/j.jmii.2016.12.008DOI Listing
December 2017

Higher mortality of severe influenza patients with probable aspergillosis than those with and without other coinfections.

J Formos Med Assoc 2017 Sep 21;116(9):660-670. Epub 2017 Jun 21.

Department of Intensive Care Medicine, Chi-Mei Medical Center, Tainan, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Background/purpose: Aspergillus-associated infection might comprise up to 23-29% of severe influenza patients from the community throughout stay in an intensive care unit (ICU). In Taiwan, cases of severe influenza with aspergillosis are increasingly reported. Therefore, we describe the relative risk of mortality among severe influenza patients with aspergillosis and other coinfections compared to severe influenza patients without Aspergillus coinfections.

Methods: We retrospectively reviewed 124 adult patients with severe influenza in a tertiary medical center in southern Taiwan from January 2015 through March 2016. The definition of probable aspergillosis required abnormal radiological findings and positive Aspergillus galactomannan (GM) antigen and/or Aspergillus isolation.

Results: Probable aspergillosis (detected throughout the whole course) and other coinfections (only community-acquired) were diagnosed in 21 (17%) and 38 (31%) of all patients respectively. Klebsiella pneumoniae (36.8%), Pseudomonas aeruginosa (31.6%) and Staphylococcus aureus (31.6%) were the most frequent isolates of other coinfections. In-ICU mortality of Aspergillus group (66.7%) was significantly higher than other coinfections (23.7%, p = 0.001) or control group without coinfections (15.4%, p < 0.001), with significant odds ratios after adjusting for important variables. The factor of GM index ≥0.6 had a 19.82 (95% CI, 4.91 to 80.07, p < 0.0001) odds of expiring in an ICU among the Aspergillus group.

Conclusion: Dual Aspergillus and influenza infection is emerging in southern Taiwan. Meanwhile, community-acquired P. aeruginosa should be listed in the common copathogens with severe influenza. The 67% mortality linked to aspergillosis highlights the need for physicians to focus attention on patients with GM ≥ 0.6.
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http://dx.doi.org/10.1016/j.jfma.2017.06.002DOI Listing
September 2017

First report of immunogenic vasculitis with Wunderlich's syndrome following influenza B infection in a previously immunocompetent woman.

J Formos Med Assoc 2018 02 7;117(2):164-165. Epub 2017 Jun 7.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jfma.2017.05.011DOI Listing
February 2018

Cephalosporin-Glycopeptide Combinations for Use against Clinical Methicillin-Resistant Isolates: Enhanced Antibacterial Activity.

Front Microbiol 2017 18;8:884. Epub 2017 May 18.

Department of Health and Nutrition, Chia Nan University of Pharmacy and ScienceTainan, Taiwan.

The empirical combination of both a beta-lactam and glycopeptide to counter potential staphylococcal pathogens may improve the clinical outcomes for cases of bacteremia. We reported comparative studies of combination effects of different cephalosporins (i.e., cefazolin, cefmetazole, cefotaxime, and cefepime) combined with glycopeptides for 34 randomly selected methicillin-resistant (MRSA) isolates by three methods, including the checkerboard, time-killing, and combination MIC measurement methods. Thirteen SCC type III isolates with a cefazolin MIC of ≥ 128 μg/mL were classified as the high-cefazolin MIC (HCM) group, whereas 13 SCC type IV and 8 SCC type V isolates were classified as the low-cefazolin MIC (LCM) group. With the checkerboard method, synergism was present for vancomycin-based combinations at 30.8-69.2 and 13.6-66.7%, as well as teicoplanin-based combinations of 38.5-84.6 and 0-47.6%, of the HCM and LCM isolates, respectively. No antagonism was noted. The inhibitory activity was evident even at a low concentration of 1/512x MIC of cephalosporin combined with sub-inhibitory concentrations (1/2x MIC) of a glycopeptide. With time-killing assays, synergism was noted at 1/2x or 1x susceptible breakpoint concentrations (SBCs) of a cephalosporin combined with 1/4 or 1/2 MIC of a glycopeptide. In the presence of 1/2 SBC of a cephalosporin, vancomycin or teicoplanin MICs decreased an average of 2.0- to 6.6- or 1.6- to 5.5-fold, respectively. With 8 μg/mL cephalosporin, the decline of glycopeptide MICs was most obvious in the presence of cefmetazole. In conclusion, cephalosporin-glycopeptide combinations at clinically achievable concentrations can exhibit synergistic antibacterial activity against clinical MRSA isolates. Such combinations require more clinical data to support their application for use in human MRSA infections.
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http://dx.doi.org/10.3389/fmicb.2017.00884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5435797PMC
May 2017

Failure of extracorporeal membrane oxygenation to rescue acute respiratory distress syndrome caused by dual infection of influenza A (H1N1) and invasive pulmonary aspergillosis.

J Formos Med Assoc 2017 07 23;116(7):563-564. Epub 2017 Feb 23.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan City, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jfma.2017.01.010DOI Listing
July 2017

High-level ambient particulate matter before influenza attack with increased incidence of Aspergillus antigenemia in Southern Taiwan, 2016.

J Microbiol Immunol Infect 2018 Feb 18;51(1):141-147. Epub 2016 Dec 18.

Department of Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan. Electronic address:

We found significant correlation between the incidence of severe influenza and Aspergillus antigenemia among medical intensive care unit patients for 7-month observation (coefficient γ=0.976, p<0.001). High-level ambient pollution was noticed for 2 months before the epidemic, highlighting that influenza patients might coinfect with aspergillosis in the community.
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http://dx.doi.org/10.1016/j.jmii.2016.09.001DOI Listing
February 2018

Fatal Dengue Myocarditis despite the Use of Extracorporeal Membrane Oxygenation.

Case Rep Infect Dis 2016 28;2016:5627217. Epub 2016 Nov 28.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Dengue is an important mosquitoes-borne viral disease which is endemic in tropics and subtropics region. Rapid spreading of disease to previously unaffected region was found in recent years. Atypical manifestations, such as myocarditis, were reported during large outbreak. There is a wide range of clinical manifestations of cardiac involvement in dengue, but rarely fatal. Here we reported a case of fulminant dengue myocarditis in fatal outcome despite cardiac mechanical support.
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http://dx.doi.org/10.1155/2016/5627217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5149615PMC
November 2016

The exploration of risk factors of concurrent bacteraemia in patients critically ill with severe dengue.

J Med Microbiol 2016 Dec 7;65(12):1505-1511. Epub 2016 Nov 7.

Department of Intensive Care Medicine, Chi-Mei Medical Center, Tainan, Taiwan, ROC.

We investigated the clinical features of intensive care unit (ICU) patients with concomitant severe dengue infection and bacteraemia to identify risk factors for this comorbidity. The records of all ICU dengue patients admitted during the period of 31 July-30 November 2015 were reviewed. Patients with 'concurrent bacteremia' (positive bacterial blood culture within 72 h of ICU admission) were identified. ICU admission was required for 142 patients, of which 22 (15.5 %) had concurrent bacteraemia. Species of the genus Streptococcus was the most common pathogens, followed by Escherichia coli then species of the genus Staphylococcus. Patients with a severe dengue infection and bacteraemia had higher APACHE II and TISS scores, C-reactive protein (CRP) levels and leukocyte counts, positive fluid balances, longer activated partial thromboplastin times (APTTs), higher lactate levels and more kidney failure, but controls (severe dengue patients without bacteraemia) had higher Glasgow Coma Scale (GCS) scores, higher albumin levels and more abdominal pain (all P<0.05). Patients with bacteraemia had a higher mortality rate than did ontrols (40.9 vs 18.3 %; P=0.018). Multiple logistic regression analysis showed that bacteraemia was significantly positively associated with the following independent predictors: higher CRP levels [adjusted odds ratio (aOR): 1.026; 95 % confidence interval (CI): 1.008-1.044; P=0.005], and longer APTTs (aOR: 1.034; 95 CI: 1.004-1.065; P=0.027). Concurrent bacteraemia is not uncommon in severe dengue patients in the ICU, and it is associated with high mortality. Higher CRP levels and longer APTTs were two independent risk factors associated with bacteraemia.
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http://dx.doi.org/10.1099/jmm.0.000388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203669PMC
December 2016

Postinfluenza A(H3N2) refractory invasive pulmonary aspergillosis.

J Formos Med Assoc 2017 05 7;116(5):404-405. Epub 2016 Oct 7.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan City, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jfma.2016.08.005DOI Listing
May 2017

Response to "Dengue fever and takotsubo syndrome: Pathophysiologic connotations".

J Formos Med Assoc 2017 01 7;116(1):68. Epub 2016 Oct 7.

Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan City, Taiwan; Department of Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan. Electronic address:

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http://dx.doi.org/10.1016/j.jfma.2016.09.003DOI Listing
January 2017

The outcomes of patients with severe dengue admitted to intensive care units.

Medicine (Baltimore) 2016 Aug;95(31):e4376

Department of Recreation and Health-Care Management, Chia Nan University of Pharmacy and Science Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan Department of Medicine, Taipei Medical University, Taipei Department of Internal Medicine, Chi-Mei Medical Center Department of Safety Health and Environment, Chung Hwa University of Medical Technology Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan.

Outcomes of adult patients with dengue infections requiring intensive care unit (ICU) admissions remain unclear. We assessed the clinical manifestations and prognostic factors of patients critically ill with severe dengue.This retrospective study was done in a tertiary referral hospital with 96 adult ICU beds. All of the patients with laboratory-confirmed severe dengue infections and admitted to the ICU were enrolled between July 31 and November 31, 2015, during the large outbreak period. The medical records of all the recruited patients were reviewed for the following information: age, gender, clinical manifestations, disease severity scores, underlying conditions, laboratory examinations, and outcomes. The primary endpoint was to find the predictors of ICU mortality.During the study period, 4787 patients with dengue infections required ICU admission. One hundred forty-three (2.99%) were critically ill (mean age: 69.7 years). Hypertension (n = 90, 62.9%) and diabetes mellitus (n = 70, 49.0%) were the 2 most common underlying diseases. Eighty critically ill patients (55.9%) had cobacterial infections, and 33 had cobacteremia. The hematologic system failed most often, followed by thoracic and cardiovascular systems. Fever was the most common presentation (n = 112; 78.3%), followed by anorexia (n = 47; 32.9%) and abdominal pain (n = 46; 32.2%). Overall, 33 patients died (mortality rate: 23.1%). Multivariate analysis showed that ICU mortality was significantly associated with lower Glasgow Coma Scale (GCS) scores, lower platelet counts before ICU discharge, and more organ failures.The number of severe dengue patients who require ICU admission remains high. The mortality rate was associated with lower GCS scores, lower platelet counts, and more organ failures. In addition, more than half of the critically ill dengue patients had comorbid bacterial infections.
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http://dx.doi.org/10.1097/MD.0000000000004376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979801PMC
August 2016