Publications by authors named "Ching-Tai Huang"

80 Publications

Role of Pneumococcal NanC in the Severe Disease of Superinfection with Influenza.

Immunohorizons 2021 Apr 28;5(4):210-218. Epub 2021 Apr 28.

Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Guishan, Taoyuan City, Taiwan;

Bacterial superinfection aggravates the disease of influenza. is the most common bacterial pathogen. Synergistic virulence has been demonstrated between influenza neuraminidase and pneumococcal NanA and NanB. NanC, the other pneumococcal neuraminidase infrequently present in clinical isolates, is not well characterized. In this study, we report that superinfection with a NanC-negative pneumococcus strain suppresses anti-influenza immunity and impairs viral clearance with higher TGF-β activation in mice. Bacterial load in the lungs also increases as the host immunity is suppressed. -positive isogenic mutant reverses wild type -mediated immune suppression and facilitates virus clearance. However, it causes more severe disease as the augmented inflammation causes collateral damage. Both virus-mediated damage and immune response-mediated inflammation are important for pathogenesis of severe influenza. Inflammation may be more critical than virus-mediated damage in influenza with bacterial superinfection.
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http://dx.doi.org/10.4049/immunohorizons.2100020DOI Listing
April 2021

Does Antimicrobial Therapy Affect Mortality of Patients with Carbapenem-Resistant Bacteriuria? A Nationwide Multicenter Study in Taiwan.

Microorganisms 2020 Dec 19;8(12). Epub 2020 Dec 19.

Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, 11217 Taipei, Taiwan.

Few clinical studies have previously discussed patients with carbapenem-resistant (CRKP) bacteriuria. This study aimed to assess the effect of antimicrobial therapy on the mortality of patients with CRKP bacteriuria. Hospitalized adults with CRKP bacteriuria were enrolled retrospectively from 16 hospitals in Taiwan during 2013 and 2014. Critically ill patients were defined as those with an Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥ 20. Multivariate Cox regression analysis was used to determine independent risk factors for 14- and 28-day mortality. Of 107 patients with CRKP bacteriuria, the 14-day and 28-day mortality was 14.0% and 25.2%, respectively. Thirty-three patients received appropriate antimicrobial therapy. In the multivariate Cox regression analysis, the APACHE II score ≥ 20 was the only independent risk factor for 14-day mortality (hazard ratio [HR]: 6.15, = 0.024). APACHE II score ≥ 20 (HR: 3.05, = 0.018) and male sex (HR: 2.57, = 0.037) were associated with 28-day mortality. Among critically ill patients with CRKP bacteriuria, appropriate antimicrobial therapy was not associated with 14-day or 28-day survival. In conclusion, in patients with CRKP bacteriuria, the use of appropriate antimicrobial therapy was not an independent factor associated with reduced mortality. Our findings may inform future antibiotic stewardship interventions for bacteriuria caused by multidrug resistant pathogens.
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http://dx.doi.org/10.3390/microorganisms8122035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767250PMC
December 2020

Therapeutic Role of Inducible Nitric Oxide Synthase Expressing Myeloid-Derived Suppressor Cells in Acetaminophen-Induced Murine Liver Failure.

Front Immunol 2020 29;11:574839. Epub 2020 Oct 29.

Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.

Background: Acetaminophen (APAP) overdose is one of the major etiologies of liver failure. Hepatocyte necrosis induced by toxic metabolites of APAP can activate proinflammatory responses, including elastase-expressing neutrophils, to exacerbate liver injury. Myeloid-derived suppressor cells (MDSCs) increased in inflammation can inhibit proinflammatory responses. Our aim is to investigate the role of MDSC in APAP-induced liver failure and the possible therapeutic application.

Methods: BLAB/c mice were injected with a sublethal/lethal dose of APAP as the murine model of liver failure. MDSCs were defined as CD11bGr-1 cells with the ability of T-cell suppression.

Results: A sublethal challenge of APAP could increase the intrahepatic MDSC and protect mice against subsequent lethal challenge of APAP, lipopolysaccharide (LPS)/D-galatosamine or concanavalin A. This protection was lost if MDSCs were depleted and inducible nitric oxide synthase (iNOS) was the key molecule in this MDSC-mediated protection. Taking advantage of these observations, different bone marrow-derived MDSCs (BM-MDSCs) were generated. Among different cytokine-treated BM-MDSCs, tumor necrosis factor alpha/LPS-primed MDSCs (TNF-α/LPS MDSCs) had the strongest liver-protection ability after adoptive transfer. Further mechanistic explorations showed, iNOS-expressing TNF-α/LPS MDSCs induced the apoptosis of activated neutrophil and decreased the intrahepatic infiltration of elastase-expressing neutrophil. Moreover, we generated MDSCs from human peripheral blood mononuclear cells (PBMCs) with similar phenotype.

Conclusion: We demonstrated the protective role of MDSCs and therapeutic effect of TNF-α/LPS MDSCs in APAP-induced liver failure. MDSC might protect against the APAP-induced liver failure by reducing the intrahepatic infiltration of activated neutrophil to limit inflammation. Therefore, a therapeutic role of MDSCs for APAP-induced liver failure was proposed.
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http://dx.doi.org/10.3389/fimmu.2020.574839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673381PMC
June 2021

Association of capsular types with carbapenem resistance, disease severity, and mortality in .

Emerg Microbes Infect 2020 Dec;9(1):2094-2104

Department of Microbiology and Immunology, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.

emerged as one of the most important pathogens that causes nosocomial infections due to its increased multidrug resistance. Identifying capsular epidemiology in can aid in the development of effective treatments and preventive measures against this emerging pathogen. Here we established a -based method, and combined it with -PCR to determine capsular types of causing nosocomial bacteraemia collected at two medical centres in Taiwan from 2015 to 2017. Among the 237 patients with bacteraemia, 98 (41.4%) isolates were resistant to carbapenems. Four prevalent capsular types (KL2, KL10, KL22, and KL52) accounted for 84.7% of carbapenem-resistant (CRAB) and 12.2% of non-CRAB. The rate of pneumonia, intensive care unit admission, APACHE II score, and Pitt bacteraemia score were higher in patients with KL2/10/22/52 infection than in those with non-KL2/10/22/52 infection. Patients with KL2/10/22/52 infection and patients with CRAB infection have a higher cumulative incidence of attributable and all-cause in-hospital 30-day mortality. On multivariate analysis, appropriate empirical antimicrobial therapy within 24 h was associated with a lower risk of 30-day attributable mortality in the KL2/10/22/52 isolates (odds ratio = 0.19, 95% CI: 0.06-0.66,  = 0.008) but not in non-KL2/10/22/52 isolates. Early recognition of carbapenem resistance-associated capsular types may help clinicians to promptly implement appropriate antimicrobial therapy for improving the outcomes in patients with CRAB bacteraemia.
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http://dx.doi.org/10.1080/22221751.2020.1822757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534287PMC
December 2020

Correlation between Negative Rapid Influenza Diagnostic Test and Severe Disease in Hospitalized Adults with Laboratory-Confirmed Influenza Virus Infection.

Am J Trop Med Hyg 2020 10;103(4):1642-1648

Division of Infectious Diseases, Department of Internal Medicine, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan.

False-negative rapid influenza diagnostic test (RIDT) results could mislead physicians to exclude an influenza diagnosis. We sought to evaluate the association between negative RIDT and intensive care unit (ICU) admission. We reviewed data from hospitalized adults with laboratory-confirmed influenza virus infections in a tertiary referral hospital in Taiwan from July 2009 to February 2011. The diagnosis was documented by real-time PCR or virus culture. Of 134 hospitalized adults infected with influenza virus, 38 (28%) were admitted to the ICU. Compared with RIDT-positive patients, the percentage of ICU admission was significantly higher among RIDT-negative patients (46% versus 13%, < 0.001). The RIDT-negative patients had higher percentages of lower respiratory symptoms and more chest radiograph infiltrates. The time interval between the RIDT and antiviral treatment was longer in RIDT-negative than RIDT-positive patients (1.94 days versus 0.03 days, < 0.001). Among patients presenting with mild illness, only a negative RIDT and delayed antiviral treatment were associated with ICU admission after adjusting for potential confounding factors. To conclude, patients with a negative RIDT were more likely to have severe disease and a delay in initiating antiviral treatment. Our findings should help improve treatment outcomes of hospitalized patients with influenza infection.
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http://dx.doi.org/10.4269/ajtmh.19-0444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543834PMC
October 2020

Heparin-induced thrombocytopenia and thrombosis in a patient with Covid-19.

Thromb Res 2020 12 3;196:11-14. Epub 2020 Aug 3.

Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, United States of America. Electronic address:

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http://dx.doi.org/10.1016/j.thromres.2020.07.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834633PMC
December 2020

Brain Computed Tomography in Stimulant Poisoning with Altered Consciousness.

J Emerg Med 2020 Jul 26;59(1):46-52. Epub 2020 May 26.

Department of Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Background: Stimulant poisoning frequently causes altered mental status (AMS) and can result in severe cerebral vascular complications. The role of noncontrast brain computed tomography (CT) in acute stimulant-poisoned patients presenting with AMS remains unclear.

Objectives: We examined the results and impacts of brain CT in acute stimulant-poisoned patients with AMS.

Methods: We performed a retrospective single-center study that included all adult patients who presented to the emergency department with stimulant poisoning and AMS (Glasgow coma scale [GCS] score <15) between January 1, 2010 and December 31, 2017. Patients who had concomitant head trauma or who presented with focal neurologic symptoms were excluded. The primary outcome was the rate of acute abnormalities on brain CT. The secondary outcomes were to identify factors that affected the decision to perform brain CT in stimulant-poisoned patients with AMS and whether obtaining the brain CT scan itself affected the patients' prognoses.

Results: The analysis included 66 patients, of whom 6 died from the poisoning. Noncontrast brain CT was performed in 31 patients and none had acute abnormalities. Patients who underwent brain CT were found to have worse GCS scores, higher body temperatures, higher intubation rates, higher admission rates, longer admission periods and intensive care unit stays, and a higher mortality rate. After adjusting for the propensity score, performing brain CT itself did not independently affect the patients' clinical outcomes.

Conclusions: Nontrauma stimulant-poisoned patients presenting with AMS and without focal neurologic symptoms were unlikely to have acute abnormalities on brain CT. Patients who underwent brain CT scans had worse consciousness and greater disease severity.
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http://dx.doi.org/10.1016/j.jemermed.2020.04.037DOI Listing
July 2020

Methicillin-resistant Staphylococcus aureus nasal colonization among HIV-infected patients in Taiwan: prevalence, molecular characteristics and associated factors with nasal carriage.

BMC Infect Dis 2020 Mar 30;20(1):254. Epub 2020 Mar 30.

Department of Medicine, Chang Gung University School of Medicine, Kweishan, Taoyuan, Taiwan.

Background: To evaluate nasal carriage, antibiotic susceptibility and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA), as well as the risk factors of MRSA colonization, in human immunodeficiency virus (HIV)-infected patients in northern Taiwan.

Methods: From September 2014 to November 2015, HIV-infected patients seeking outpatient care at four hospitals were eligible for this study. A nasal specimen was obtained from each subject for the detection of S. aureus and a questionnaire was completed by each subject. MRSA isolates once identified were characterized.

Results: Of 553 patients surveyed, methicillin-susceptible S. aureus (MSSA) was detected in 119 subjects (21.5%) and MRSA in 19 subjects (3.4%). Female gender, injection drug use, smoking, hepatitis C virus carrier, cancer and antibiotic use within 1 year were positively associated with MRSA colonization. By multivariate analysis, only cancer (adjust odds ratio (aOR) 7.78, [95% confidence interval (CI), 1.909-31.731]) and antibiotic use within 1 year (aOR 3.89, [95% CI, 1.219-12.433]) were significantly associated with MRSA colonization. Ten isolates were characterized as sequence type (ST) 59/staphylococcal chromosome cassette (SCC) IV or V, endemic community strains in Taiwan, four isolates as ST 8/SCCmec IV (USA 300) and one isolate as ST 239/SCCmec IIIA, a hospital strain. All the community-associated MRSA isolates were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX).

Conclusions: Nasal MRSA carriage in HIV-infected patients seeking outpatient care was low (3.4%) in northern Taiwan. Most of the colonizing isolates were genetically endemic community strains and exhibited high susceptibility to TMP-SMX and fluoroquinolones. Cancer and antibiotic use within 1 year were associated with MRSA colonization.
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http://dx.doi.org/10.1186/s12879-020-04979-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106609PMC
March 2020

Genomic Insight into the Spread of Meropenem-Resistant Streptococcus pneumoniae Spain-ST81, Taiwan.

Emerg Infect Dis 2020 04;26(4):711-720

Incidence of invasive pneumococcal disease caused by antimicrobial-resistant Streptococcus pneumoniae types not included in pneumococcal conjugate vaccines has increased, including a penicillin- and meropenem-resistant serotype 15A-ST63 clone in Japan. During 2013-2017, we collected 206 invasive pneumococcal isolates in Taiwan for penicillin and meropenem susceptibility testing. We found serotypes 15B/C-ST83 and 15A-ST63 were the most prevalent penicillin- and meropenem-resistant clones. A transformation study confirmed that penicillin-binding protein (PBP) 2b was the primary meropenem resistance determinant, and PBP1a was essential for high-level resistance. The rate of serotype 15B/C-ST83 increased during the study. All 15B/C-ST83 isolates showed an ermB macrolide resistance genotype. Prediction analysis of recombination sites revealed 12 recombination regions in 15B/C-ST83 compared with the S. pneumoniae Spain-ST81 genome. Pneumococcal clones rapidly recombine to acquire survival advantages and undergo local expansion under the selective pressure exerted by vaccines and antimicrobial drugs. The spread of 15B/C-ST83 is alarming for countries with high antimicrobial pressure.
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http://dx.doi.org/10.3201/eid2604.190717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101100PMC
April 2020

Arguments in favour of remdesivir for treating SARS-CoV-2 infections.

Int J Antimicrob Agents 2020 04 6;55(4):105933. Epub 2020 Mar 6.

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:

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http://dx.doi.org/10.1016/j.ijantimicag.2020.105933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135364PMC
April 2020

The antimicrobial susceptibility in adult invasive pneumococcal disease in the era of pneumococcus vaccination: A hospital-based observational study in Taiwan.

J Microbiol Immunol Infect 2020 Dec 14;53(6):836-844. Epub 2020 Feb 14.

Chang Gung University College of Medicine, Taoyuan, Taiwan; Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. Electronic address:

Background: A regional antibiotic susceptibility data of common pathogens is crucial to first-line physician for clinical judgment and appropriate selection of antimicrobial agents. The aim of this study is to update the epidemiology data of drug resistance of pneumococcus causing invasive pneumococcal disease (IPD) in adults.

Methods: From the logbooks of microbiology laboratories, we retrospectively retrieved Streptococcus pneumoniae isolates, collected from normally sterile sites in adult patients in three hospitals in Taiwan from July 2011 to June 2015. Antibiotic resistance and serotypes of the isolates and clinical manifestations were further analyzed.

Results: A total of 150 non-duplicated isolates were collected. According to CLSI meningitis breakpoint, the proportion of ceftriaxone non-susceptible pneumococcus (CNSP) showed an increasing trend from 4.5% in 2011 to > 40% in 2013-2015 (p = 0.007). Serotypes 19A and 23F were significantly associated with CNSP. Imipenem and meropenem had a relative low susceptible rate of 36.7% and 50.7%, respectively. Serotypes 6A, 14, 19A and 19F were significantly associated with the non-susceptibility to these carbepanems.

Conclusion: The increase in the prevalence of CNSP using meningitis breakpoint was observed. For treating pneumococcal meningitis, empirical monotherapy with ceftriaxone might not be adequate. Imipenem and meropenem might not be a good choice for empirical treatment of adult IPDs. Antibiotic resistance of pneumococcus to ceftriaxone, cefepime, imipenem and meropenem were associated with 13-velent pneumococcal conjugate vaccine serotypes.
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http://dx.doi.org/10.1016/j.jmii.2020.01.003DOI Listing
December 2020

Effect of aloin on viral neuraminidase and hemagglutinin-specific T cell immunity in acute influenza.

Phytomedicine 2019 Nov 4;64:152904. Epub 2019 Apr 4.

Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital, Guishan- 33333, Taoyuan City, Taiwan. Electronic address:

Background: Millions of people are infected by the influenza virus worldwide every year. Current selections of anti-influenza agents are limited and their effectiveness and drug resistance are still of concern.

Purpose: Investigation on in vitro and in vivo effect of aloin from Aloe vera leaves against influenza virus infection.

Methods: In vitro antiviral property of aloin was measured by plaque reduction assay in which MDCK cells were infected with oseltamivir-sensitive A(H1N1)pdm09, oseltamivir-resistant A(H1N1)pdm09, H1N1 or H3N2 influenza A or with influenza B viruses in the presence of aloin. In vivo activity was tested in H1N1 influenza virus infected mice. Aloin-mediated inhibition of influenza neuraminidase activity was tested by MUNANA assay. Aloin treatment-mediated modulation of anti-influenza immunity was tested by the study of hemagglutinin-specific T cells in vivo.

Results: Aloin significantly reduced in vitro infection by all the tested strains of influenza viruses, including oseltamivir-resistant A(H1N1)pdm09 influenza viruses, with an average IC value 91.83 ± 18.97 μM. In H1N1 influenza virus infected mice, aloin treatment (intraperitoneal, once daily for 5 days) reduced virus load in the lungs and attenuated body weight loss and mortality. Adjuvant aloin treatment also improved the outcome with delayed oseltamivir treatment. Aloin inhibited viral neuraminidase and impeded neuraminidase-mediated TGF-β activation. Viral neuraminidase mediated immune suppression with TGF-β was constrained and influenza hemagglutinin-specific T cell immunity was increased. There was more infiltration of hemagglutinin-specific CD4+ and CD8+ T cells in the lungs and their production of effector cytokines IFN-γ and TNF-α was boosted.

Conclusion: Aloin from Aloe vera leaves is a potent anti-influenza compound that inhibits viral neuraminidase activity, even of the oseltamivir-resistant influenza virus. With suppression of this virus machinery, aloin boosts host immunity with augmented hemagglutinin-specific T cell response to the infection. In addition, in the context of compromised benefit with delayed oseltamivir treatment, adjuvant aloin treatment ameliorates the disease and improves survival. Taken together, aloin has the potential to be further evaluated for clinical applications in human influenza.
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http://dx.doi.org/10.1016/j.phymed.2019.152904DOI Listing
November 2019

Clinical features, microbiological epidemiology and recommendations for management of cellulitis in extremity lymphedema.

J Surg Oncol 2020 Jan 2;121(1):25-36. Epub 2019 Jul 2.

Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Background: This high volume, single center study investigated the prevalence, bacterial epidemiology, and responsiveness to antibiotic therapy of cellulitis in extremity lymphedema.

Methods: From 2003 to 2018, cellulitis events from a cohort of 420 patients with extremity lymphedema were reviewed. Demographics, lymphedema grading, symptoms, inflammatory markers, cultures and antibiotic therapy regimens were compiled from cellulitis episodes data. Univariate and multivariate analyses were performed for detailed analysis.

Results: A total of 131 separate episodes of cellulitis were recorded from 43 (81.1%) lower limb and 10 (19.9%) upper limb lymphedema patients. The prevalence and recurrence rates for cellulitis in lymphedema patients were 12.6% (53 of 420) and 56.6% (30 of 53), respectively. The most common findings were increased limb circumference (127 of 131; 96.9%) and abnormal C-reactive protein (CRP) level (86 of 113; 76.1%). Blood cultures were obtained in 79 (60.3%) incidents, with 9 (11.4%) returning positive. Streptococcus agalactiae was the most isolated bacterium (5 of 9; 55.5%).

Conclusions: The cellulitis prevalence and recurrence rate in extremity lymphedema were 12.6%, and 56.6%, respectively. Strongest indicators of cellulitis were increased affected limb circumference and elevated CRP level. Empiric antibiotic therapy began with coverage for Steptococcus species before broadening to anti-Methicillin-resistant Staphylococcus aureus and anti-Gram negatives if needed for effective treatment of extremity lymphedema cellulitis.
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http://dx.doi.org/10.1002/jso.25525DOI Listing
January 2020

Randomized Noninferiority Trial of Cefoperazone-Sulbactam versus Cefepime in the Treatment of Hospital-Acquired and Healthcare-Associated Pneumonia.

Antimicrob Agents Chemother 2019 08 25;63(8). Epub 2019 Jul 25.

School of Medicine, National Yang-Ming University, Taipei, Taiwan

Cefoperazone, a third-generation cephamycin with broad-spectrum antibacterial activity and the ability to permeate bacterial cell membranes, is active against commonly encountered multidrug-resistant pathogens for hospital-acquired pneumonia (HAP) and health care-associated pneumonia (HCAP). To clarify the clinical effects of cefoperazone-sulbactam in the treatment of HAP and HCAP, we conducted an open-label, randomized, noninferiority trial that recruited patients aged ≥18 years suffering HAP/HCAP. Participants were randomly assigned to the cefoperazone-sulbactam (2 g of each per 12 h) or cefepime (2 g per 12 h) arm. Clinical and microbiological responses were evaluated at early posttherapy and test-of-cure visits. Recruited patients were allocated to subpopulations for intent-to-treat ( = 154), per-protocol ( = 147), and safety ( = 166) analyses. Intent-to-treat analysis demonstrated that (i) at the early posttherapy visit, 87.3% of patients receiving cefoperazone-sulbactam and 84.3% of patients receiving cefepime achieved clinical improvement or cure (risk difference of 3.0%; 95% confidence interval [CI], -9.0% to 15.0%), and (ii) at the test-of-cure visit, 73.1% of patients receiving cefoperazone-sulbactam and 56.8% of patients receiving cefepime were assessed as cured (risk difference of 16.3%; 95% CI, 0.0% to 33.0%). These results indicated the noninferiority of cefoperazone-sulbactam to cefepime, which was confirmed by per-protocol analysis. The chest radiographic consolidation/infiltration resolution rate, microbiological eradiation rate, and percentage of adverse events were comparable in both groups. Serious adverse events were rare, and none was judged to be related to the study drugs. Cefoperazone-sulbactam at 2 g every 12 h was noninferior to cefepime at 2 g every 2 h for patients with HCAP.
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http://dx.doi.org/10.1128/AAC.00023-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658783PMC
August 2019

Appropriate Treatment for Bloodstream Infections Due to Carbapenem-Resistant and : A Nationwide Multicenter Study in Taiwan.

Open Forum Infect Dis 2019 Feb 17;6(2):ofy336. Epub 2018 Dec 17.

Division of Infectious Diseases, Sijhih Cathy General Hospital, New Taipei City, Taiwan.

Background: In a multicenter study from Taiwan, we aimed to investigate the outcome of patients who received different antimicrobial therapy in carbapenem-resistant Enterobacteriaceae bloodstream infections and proposed a new definition for tigecycline use.

Methods: Patients from 16 hospitals in Taiwan who received appropriate therapy for bloodstream infections due to carbapenem-resistant and were enrolled in the study between January 2012 and June 2015. We used a cox proportional regression model for multivariate analysis to identify independent risk factors of 14-day mortality. Tigecycline was defined as appropriate when the isolates had a minimum inhibitory concentration (MIC) ≤0.5 mg/L, and we investigated whether tigecycline was associated with mortality among patients with monotherapy.

Results: Sixty-four cases with carbapenem-resistant (n = 50) and (n = 14) bloodstream infections were analyzed. Of the 64 isolates, 17 (26.6%) had genes that encoded carbapenemases. The 14-day mortality of these cases was 31.3%. In the multivariate analysis, Charlson Comorbidity Index (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.42; = .022) and colistin monotherapy (HR, 5.57; 95% CI, 2.13-14.61; < .001) were independently associated with 14-day mortality. Among the 55 patients with monotherapy, the 14-day mortality was 30.9% (n = 17). Tigecycline use was not associated with mortality in the multivariate analysis.

Conclusions: Tigecycline monotherapy was a choice if the strains exhibited MIC ≤0.5 mg/L, and colistin monotherapy was not suitable. Our findings can initiate additional clinical studies regarding the efficacy of tigecycline in carbapenem-resistant Enterobacteriaceae infections.
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http://dx.doi.org/10.1093/ofid/ofy336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362312PMC
February 2019

The clinical impact of patients with bloodstream infection with different groups of Viridans group streptococci by using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).

Medicine (Baltimore) 2018 Dec;97(50):e13607

Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou.

The accuracy of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for identifying viridans group streptococcus (VGS) was improving. However, the clinical impact of identifying VGS had not been well recognized. Our study had comprehensively studied the clinical manifestations and outcome of VGS blood stream infection by using MALDI-TOF MS for identification.This retrospective study enrolled 312 adult patients with a monomicrobial blood culture positive for VGS. Blood culture was examined through MALDI-TOF MS.The most common VGS species were the Streptococcus anginosus group (38.8%) and Streptococcus mitis group (22.8%). Most species showed resistance to erythromycin (35.6%), followed by clindamycin (25.3%) and penicillin (12.5%). Skin and soft tissue infection and biliary tract infection were significantly related to S. anginosus group bacteremia (P = .001 and P = .005, respectively). S. mitis group bacteremia was related to infective endocarditis and bacteremia with febrile neutropenia (P = .005 and P < .001, respectively). Infective endocarditis was also more likely associated with S. sanguinis group bacteremia (P = .009). S. anginosus group had less resistance rate to ampicillin, erythromycin, clindamycin, and ceftriaxone (P = .019, <.001, .001, and .046, respectively). A more staying in intensive care unit, underlying solid organ malignancy, and a shorter treatment duration were independent risk factors for 30-day mortality. This study comprehensively evaluated different VGS group and their clinical manifestations, infection sources, concomitant diseases, treatments, and outcomes. Categorizing VGS into different groups by MALDI-TOF MS could help clinical physicians well understand their clinical presentations.
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http://dx.doi.org/10.1097/MD.0000000000013607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320099PMC
December 2018

Induction of liver-specific intrahepatic myeloid cells aggregation expands CD8 T cell and inhibits growth of murine hepatoma.

Oncoimmunology 2018;7(12):e1502129. Epub 2018 Sep 19.

School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Toll-Like Receptor 9 (TLR9) stimulation selectively triggers the formation of a cell cluster termed intrahepatic myeloid aggregation for T cell expansion" (iMATE) in a mouse chronic viral hepatitis model. iMATE expands cytotoxic T cells and controls viral hepatitis infection. The liver-specific immune response prompted this investigation of whether the effect could control tumor growth in the murine hepatic tumor model. Murine hepatic BNL cells were used to establish an orthotropic liver tumor model. We found that intravenous infusion of TLR 9 agonist, CpG oligodeoxynucleotide (ODN) induced iMATE formation in non-tumor parts of liver and suppressed the murine BNL tumor growth. The ratio of intra-tumor CD8 T cells have increased after CpG ODN. These cells expressed higher levels of effector and checkpoint molecules, and produce more Th1 cytokine upon ex vivo stimulation. The CD11bLy6CLy6G subset of CD11b myeloid cells in the tumor microenvironment has increased. Both CD11bLy6CLy6G and CD11bLy6CLy6G subsets expressed higher level of interferon-gamma post CpG ODN treatment, although still presented a suppressive phenotype. Their suppressive ability was decreased, instead, the targeted CD8 T cell proliferation was promoted at a higher dose of CD11bLy6CLy6G cells. The phenomenon was further proven in DEN induced liver tumor model. In conclusion, systemic CpG ODN treatment induced iMATE formation that expanded effector CD8 T cells to control tumor growth in the mouse hepatic tumor model. This novel strategy provides a new rationale for liver-specific tumor immunotherapy.
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http://dx.doi.org/10.1080/2162402X.2018.1502129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279338PMC
September 2018

Clinical characteristics of patients with laboratory-confirmed influenza A(H1N1)pdm09 during the 2013/2014 and 2015/2016 clade 6B/6B.1/6B.2-predominant outbreaks.

Sci Rep 2018 10 23;8(1):15636. Epub 2018 Oct 23.

Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

A novel pandemic influenza A(H1N1)pdm09 virus emerged in 2009 globally, and it continues to circulate in humans. The National Influenza Surveillance Network in Taiwan identified five A(H1N1)pdm09-predominant seasons, representing the 2009/2010, 2010/2011, 2012/2013, 2013/2014, and 2015/2016 outbreaks from 2009 to 2016. Independently, a retrospective cohort study (which enrolled 639 infected patients during the five seasons) was conducted at Chang Gung Memorial Hospital to explore the risk factors associated with influenza A(H1N1)pdm09-related complications. A phylogenetic analysis of hemagglutinin (HA) sequences showed that the circulating A(H1N1)pdm09 virus belonged to clades 1, 2, and 8 in 2009/2010; clades 3, 4, 5, and 7 in 2010/2011; clades 7 and 6C in 2012/2013; clades 6B in 2013/2014; and 6B/6B.1/6B.2 in 2015/2016. Compared to individuals infected in non-6B/6B.1/6B.2 seasons (2009/2010, 2010/2011, and 2012/2013), those infected in 6B/6B.1/6B.2 seasons (2013/2014 and 2015/2016) were at higher risk for influenza-related complications (adjusted odds ratio [aOR]: 1.6, 95% confidence interval [CI]: 1.0-2.8), pneumonia (aOR: 1.78, 95% CI: 1.04-3.04), mechanical ventilation (aOR: 2.6, 95% CI: 1.2-5.6), and acute respiratory distress syndrome (aOR: 5.5, 95% CI: 1.9-15.9). For the increased severity of infection during the influenza A(H1N1)pdm09 clade 6B/6B.1/6B.2 seasons, aspects related to the antigenic change of A(H1N1)pdm09 virus, immune response of the host, and environmental factors required further investigation.
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http://dx.doi.org/10.1038/s41598-018-34077-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199313PMC
October 2018

Diagnostic performance of the Sofia® influenza A+B fluorescent immunoassay in adult outpatients in Northern Taiwan.

J Med Virol 2018 06 12;90(6):1010-1018. Epub 2018 Mar 12.

Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.

To evaluate the diagnostic performance of the Sofia influenza A+B fluorescent immunoassay (Sofia FIA), we performed a prospective study at the Chang Gung Memorial Hospital in Taiwan from January 2012 to December 2013. Patients who presented at out-patient clinics or the emergency department with influenza-like illness were included. Upper respiratory tract specimens were collected from oropharynx or nasopharynx. Performance of the Sofia FIA was compared to that of the Formosa One Sure Flu A/B Rapid Test. A Real-time reverse transcriptase-polymerase chain reaction assay (RT-PCR) and/or virus culture were used as reference standards. Of the 109 enrolled patients, the sensitivity, specificity, positive, and negative predictive values of the Sofia FIA to detect influenza A virus were 82%, 89%, 77%, and 89%, respectively. These parameters were 100% when the samples were from nasopharynx. The positive predictive value for influenza B virus detection was 29%. The sensitivity of the Sofia FIA for detection of influenza A virus was 93% between days 2 and 4 after onset of symptoms. For specimens with low viral loads (RT-PCR cycle threshold between 30 and 34.9), the sensitivity of The Sofia FIA was 83% (10/12). The Sofia FIA performed effectively in detecting influenza A virus infection. With nasopharyngeal samples, the performance was comparable to RT-PCR. Although influenza viral load typically decreases with time, the Sofia FIA was sensitive enough to identify influenza infecting patients presenting after several days of illness. However, a high false positive rate limits the assay's usefulness to identify influenza B virus infection.
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http://dx.doi.org/10.1002/jmv.25043DOI Listing
June 2018

Treatment outcome of non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae infections: a multicenter study in Taiwan.

Eur J Clin Microbiol Infect Dis 2018 Apr 14;37(4):651-659. Epub 2017 Dec 14.

Division of Infectious Diseases, Sijhih Cathy General Hospital, New Taipei City, Taiwan.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are associated with high mortality, and experiences with its treatment are usually based on carbapenemase-producing strains. Non-carbapenemase-producing CRKP is of clinical significance, but relevant studies are lacking. This nationwide study aimed to evaluate the outcome of antimicrobial therapy in patients with non-carbapenemase-producing CRKP infections. Patients with non-carbapenemase-producing CRKP infections were enrolled from 16 hospitals during January 2013 to December 2014 in Taiwan. Carbapenem resistance was defined as reduced susceptibility with a minimum inhibitory concentration of ≥2 mg/L for imipenem or meropenem. The resistance mechanisms of CRKP isolates were analyzed, and the clinical data of these patients were collected retrospectively. Independent risk factors of 14-day morality were determined by Cox regression analysis. A total of 99 patients with non-carbapenemase-producing CRKP infections were enrolled, and 14-day mortality was 27.3%. Among 67 patients treated with appropriate antimicrobial therapy, most (n = 61) patients received monotherapy. The 14-day mortality was lower in patients treated with appropriate monotherapy (21.3%) than in those with inappropriate therapy (37.5%). The multivariate regression model identified monotherapy (hazard ratio [HR], 0.30; 95% confidence interval [CI], 0.13-0.71; P = 0.005) as protective factor, and APACHE II scores (HR, 1.09; 95% CI, 1.01-1.18; P = 0.022) as risk factor associated with 14-day mortality. Tigecycline, colistin, and carbapenem were the most commonly used drugs in monotherapy. This study provides evidence supporting the efficacy of monotherapy in the treatment of non-carbapenemase-producing CRKP infections, and provides a future target for antibiotics stewardship for CRKP infection.
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http://dx.doi.org/10.1007/s10096-017-3156-8DOI Listing
April 2018

Risk factors and outcomes of candidemia caused by Candida parapsilosis complex in a medical center in northern Taiwan.

Diagn Microbiol Infect Dis 2018 Jan 6;90(1):44-49. Epub 2017 Oct 6.

Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address:

To investigate the risk factors and outcomes associated with Candida parapsilosis candidemia, a retrospective study was conducted at a tertiary medical center in northern Taiwan. Patients with C. parapsilosis candidemia and corresponding controls with C. albicans candidemia were chosen and their demographics, comorbidities, risk factors, and clinical outcomes were reviewed. Antifungal susceptibility tests were performed using the Sensititre YeastOne colorimetric system. Matrix-assisted laser desorption ionization-time of flight mass spectrometry was used to classify the genomic species. Of the 270 candidemias found in 253 patients, C. albicans was the most common Candida species isolated (43.0%), followed by C. parapsilosis (22.6%), C. tropicalis (17.4%), and C. glabrata (10.0%). The 30-day mortality of C. parapsilosis candidemia was significantly lower than that of C. albicans candidemia (21.7% vs. 53.9%, P<0.001). C. parapsilosis was positively associated with antifungal agent exposure [OR 7.261 (95% CI, 1.603-32.879), P=0.010], but negatively associated with Candida colonization [OR 0.303 (95% CI, 0.123-0.745), P=0.009], and immunosuppressant use [OR 0.264 (95% CI, 0.099-0.705), P=0.008]. In-hospital mortality was associated with the Sequential Organ Failure Assessment Score [OR 1.255 (95% CI, 1.002-1.573), P=0.048]. The clinical outcomes did not differ across genomic species and in the minimum inhibitory concentrations of fluconazole.
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http://dx.doi.org/10.1016/j.diagmicrobio.2017.10.002DOI Listing
January 2018

Clinical characteristics and treatment outcomes of vancomycin-resistant Enterococcus faecium bacteremia.

J Microbiol Immunol Infect 2018 Dec 5;51(6):705-716. Epub 2017 Oct 5.

Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address:

Background: Vancomycin-resistant Enterococcus faecium (VRE-fm) bacteremia causes significant mortality in hospitalized patients. We sought to investigate clinical characteristics, treatment outcomes, and microbiological eradication associated with VRE-fm bacteremia.

Methods: A retrospective cohort study was conducted and included 210 adult patients admitted between January 1, 2011 and December 31, 2015.

Results: The mean Pitt bacteremia score was 4.7. ICU stay (48.6%) and mechanical ventilation (46.2%) were common. Diabetes mellitus was the most common concomitant disease (43.3%), followed by malignancies, including hematologic malignancies (14.3%) and solid cancers (28.1%). The 14-day and 28-day mortality rates were 37.1% and 50.5%, respectively. Linezolid or daptomycin treatment for at least 10 days and higher Pitt bacteremia scores were independently associated with 14-day and 28-day mortality. Longer treatment duration of linezolid or daptomycin predicted microbiological eradication independently. Daptomycin-treated patients tended to have higher 14-day and 28-day mortality, and lower microbial eradication rates (20.8% versus 8.7%; 40.6% versus 26.1%; 14.1% versus 26.1%; respectively) than linezolid-treated patients, and cumulative survival rates at 14 and 28 days tended to be lower in patients who received low-dose daptomycin (<10 mg/kg/day) than that in those who received linezolid and high-dose daptomycin (≥10 mg/kg/day); however, the differences were not statistically significant.

Conclusion: Higher disease severity and inappropriate treatment were associated with increased mortality and longer treatment duration of linezolid or daptomycin was associated with microbial eradication for the patient with VRE-fm bacteremia.
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http://dx.doi.org/10.1016/j.jmii.2017.08.025DOI Listing
December 2018

Acquisition and clearance of multidrug resistant Acinetobacter baumannii on healthy young adults concurrently burned in a dust explosion in Taiwan: the implication for antimicrobial stewardship.

BMC Infect Dis 2017 08 30;17(1):598. Epub 2017 Aug 30.

Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital and Chang Gung University, 5 Fu-Shin St., Kweishan, 333, Taoyuan, Taiwan.

Background: Information is limited about the effect of restricted carbapenem use on clearance of multi-drug resistant Acinetobacter baumannii (MDRAB). We sought to determine the time effect of antibiotic exposure on multi-drug resistant Acinetobacter baumannii (MDRAB) acquisition and clearance.

Methods: We conducted a retrospective observational study at the intensive care units of a tertiary medical center. Forty-two of a cohort of previously healthy young adults who were concurrently burned by a dust explosion was included. Cases consisted of those from whom MDRAB was isolated during hospitalization. Controls consisted of patients from whom MDRAB was not isolated in the same period. Use of antimicrobial agents was compared based on days of therapy per 1,000 patient-days (DOT/1,000PD). A 2-state Markov multi-state model was used to estimate the risk of acquisition and clearance of MDRAB.

Results: MDRAB was discovered in 9/42 (21.4%) individuals. The cases had significantly higher use of carbapenem (652 DOT/1,000PD vs. 385 DOT/1,000PD, P < 0.001) before MDRAB isolation. For the cases, clearance of MDRAB was associated with lower use of carbapenem (469 DOT/1,000PD vs. 708 DOT/1,000PD, P = 0.003) and higher use of non-carbapenem beta-lactam (612 DOT/1,000PD vs. 246 DOT/1,000PD, P <0.001). In multi-state model, each additional DOT of carbapenem increased the hazard of acquiring MDRAB (hazard ratio (HR), 1.08; 95% confidence interval (CI) 1.01-1.16) and each additional DOT of non-carbapenem beta-lactam increased the protection of clearing MDRAB (HR, 1.25; 95% CI 1.07-1.46).

Conclusions: Both acquisition and clearance of MDRAB were related to antibiotic exposure in a homogeneous population. Our findings suggest that early discontinuation of carbapenem could be an effective measure in antibiotic stewardship for the control of MDRAB spreading.
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http://dx.doi.org/10.1186/s12879-017-2682-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575946PMC
August 2017

Influence of borderline cefepime MIC on the outcome of cefepime-susceptible Pseudomonas aeruginosa bacteremia treated with a maximal cefepime dose: a hospital-based retrospective study.

Ann Clin Microbiol Antimicrob 2017 Jul 24;16(1):52. Epub 2017 Jul 24.

Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, 5 Fu-Shin Street, Gueishan 333, Taoyuan, Taiwan.

Background: We assessed the influence of current cefepime minimal inhibitory concentration (MIC) breakpoints and the maximal cefepime dose on treatment outcomes in patients with bacteremia caused by cefepime-susceptible Pseudomonas aeruginosa.

Methods: Adult patients hospitalized between July 2010 and June 2014 with a positive blood culture for cefepime-susceptible P. aeruginosa and receipt of cefepime as the primary therapy throughout the course were reviewed. Cefepime Etest MICs and clinical outcomes for P. aeruginosa bacteremia were reviewed to identify the MIC breakpoint influencing treatment outcomes.

Results: Of the 90 patients enrolled, 49 (54.4%) were male (mean age = 66.8 years). The mean Acute Physiology and Chronic Health Evaluation II score was 22.01. Sixty patients (66.7%) received a maximal cefepime dose, and the 30-day crude mortality rate was 36.7%. MIC of cefepime for P. aeruginosa was 8 mg/L. The cumulative survival rate at 30 days revealed that a lower cefepime MIC (<4 mg/L) for P. aeruginosa was associated with a higher survival rate than a higher MIC (≥4 mg/L) (72.6% vs. 23.5%, p < 0.0001). A cefepime MIC of ≥4 mg/L and age were independent risk factors for mortality, whereas the maximal cefepime dose was the independent protective factor. The use of a maximal cefepime dose did not improve the outcomes of patients with P. aeruginosa bacteremia at a MIC of ≥4 mg/L.

Conclusions: A cefepime MIC of 4 mg/L may predict an unfavorable outcome among patients with serious infections caused by P. aeruginosa, even the MICs still within the CLSI susceptibility breakpoint.
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http://dx.doi.org/10.1186/s12941-017-0227-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525263PMC
July 2017

Rapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model.

Sci Rep 2017 06 23;7(1):4136. Epub 2017 Jun 23.

Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kweishan, 33333, Taoyuan, Taiwan.

Influenza virus infection often causes severe disease and acute respiratory distress syndrome. It is a common belief that overwhelming immune response contributes to the severe illness. Physicians and researchers have put forth immune modulation as salvage therapy for better recovery. However, empiric corticosteroid failed in both humans and animal models. Reported success with Rapamycin in humans prompted a comprehensive animal study and mechanistic dissection. Here we report the effect of Rapamycin alone or in combination with Oseltamivir for severe influenza in BALB/c mice. We found that Rapamycin had no antiviral effect against H1N1, H3N2 and novel-H1N1 influenza viruses in vitro. Rapamycin alone aggravated the severe disease of PR8 H1N1 influenza virus infection in mice. Timely Oseltamivir anti-viral therapy abolished the disease. Delayed Oseltamivir treatment could not prevent severe illness and Rapamycin adjuvant was associated with exacerbated disease. Rapamycin adjuvant suppressed influenza hemagglutinin antigen-specific T cell immunity and impaired virus clearance from the lungs. It also resulted in intensified lung pathology with increased intra-alveolar edema and hyaline deposition. Rapamycin may work as the salvage therapy for severe influenza but it is very difficult to define the appropriate window for such treatment to take effect.
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http://dx.doi.org/10.1038/s41598-017-04365-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482837PMC
June 2017

Impact of pneumococcal conjugate vaccine in children on the serotypic epidemiology of adult invasive pneumococcal diseases in Taiwan.

J Microbiol Immunol Infect 2018 Jun 18;51(3):332-336. Epub 2016 Dec 18.

Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address:

Background: Invasive pneumococcal disease (IPD) causes significant morbidity and mortality, especially in children and older adults. Pneumococcal 7-valent and 13-valent conjugate vaccines (PCV7 and PCV13) were introduced in Taiwan in 2005 and 2011, respectively, for children. This study was conducted to evaluate the impact of PCV administered in children on adult IPD.

Methods: From the logbooks of microbiology laboratories, we retrospectively retrieved Streptococcus pneumoniae isolates, collected from normally sterile sites in adult patients. One hundred and fifty-seven consecutive, nonduplicated isolates were collected from one hospital during 2001 and 2003 (pre-PCV period) and 150 isolates from three hospitals from July 2011 to June 2015 (post-PCV period). Serotypes were determined by Quellung test.

Results: Among the 307 isolates, 31 serotypes/serogroups were identified. PCV7 serotypes, particularly types 14 (31.2%), 23F (19.7%) and 6B (12.7%) dominated in the pre-PCV period (78.3%) but significantly decreased in the post-PCV period (36%) (p < 0.01). PCV13 specific serotypes (PCV13-PCV7) significantly increased from 7% of the isolates in the pre-PCV period to 28.7% of the isolates in the post-PCV period (p < 0.001), particularly type 19A (from 0.6% to 10%) and 6A (from 0 to 6.7%). Serotype 15B also increased significantly from 0.6% to 6.7% (p < 0.01). Nonvaccine serotypes increased significantly in the post-PCV period (11.5% to 22.0%, p < 0.05), particularly type 15A (from 0 to 4.4%, p < 0.01).

Conclusion: Serotype distribution of adult IPD in Taiwan has evolved after the introduction of PCV in children, indicating an indirect impact in adults. Continuous surveillance after the PCV13 vaccination program in children is needed.
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http://dx.doi.org/10.1016/j.jmii.2016.08.009DOI Listing
June 2018

Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs.

Sci Rep 2016 09 6;6:32973. Epub 2016 Sep 6.

Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan- 33333, Taiwan.

Sterilizing immunity is a unique immune status, which prevents effective virus infection into the host. It is different from the immunity that allows infection but with subsequent successful eradication of the virus. Pre-infection induces sterilizing immunity to homologous influenza virus challenge in ferret. In our antigen-specific experimental system, mice pre-infected with PR8 influenza virus through nasal route are likewise resistant to reinfection of the same strain of virus. The virus is cleared before establishment of effective infection. Intramuscular influenza virus injection confers protection against re-infection with facilitated virus clearance but not sterilizing immunity. Pre-infection and intramuscular injection generates comparable innate immunity and antibody response, but only pre-infection induces virus receptor reduction and efficient antigen-specific T cell response in the lungs. Pre-infection with nH1N1 influenza virus induces virus receptor reduction but not PR8-specific T cell immune response in the lungs and cannot prevent infection of PR8 influenza virus. Pre-infection with PR8 virus induced PR8-specific T cell response in the lungs but cannot prevent infection of nH1N1 virus either. These results reveal that antigen-specific T cell immunity is required for sterilizing immunity.
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http://dx.doi.org/10.1038/srep32973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011745PMC
September 2016

Tigecycline-based versus sulbactam-based treatment for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex.

BMC Infect Dis 2016 08 5;16:374. Epub 2016 Aug 5.

Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, 5 Fu-Shin St., Gueishan, 333, Taoyuan, Taiwan.

Background: The treatment options for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (MDR Acb) complex are limited, and the optimal treatment has not been established.

Methods: To compare the efficacy of tigecycline-based with sulbactam (or ampicillin/sulbactam)-based therapy for pneumonia involving MDR Acb complex, we conducted a retrospective study comparing 84 tigecycline-treated adult patients during the period August 2007 to March 2010 with 84 sulbactam or ampicillin/sulbactam-treated adult patients during the period September 2004 to July 2007. Both groups had the matched Acute Physiology and Chronic Health Evaluation (APACHE) II score and received treatment for at least 7 days.

Results: The mean APACHE II score was 20.1 for both groups. More patients in sulbactam group had ventilator use (89.3 % versus 69.0 %), bilateral pneumonia (79.8 % versus 60.7 %) and combination therapy (84.5 % versus 53.6 %), particularly with carbapenems (71.4 % versus 6.0 %), while more patients in tigecycline group had delayed treatment (41.7 % versus 26.2 %) (P <0.05). At the end of treatment, more patients in sulbactam group had airway MDR Acb complex eradication (63.5 % versus 33.3 %, P <0.05). The clinical resolution rate was 66.7 % for both groups. The mortality rate during treatment was 17.9 % in sulbactam group, and 25.0 % in tigecycline group (P = 0.259). The multivariate analysis showed that bilateral pneumonia was the only independent predictor for mortality during treatment (adjusted odds ratio, 2.717; 95 % confidence interval, 1.015 to 7.272).

Conclusions: Patients treated with either tigecycline-based or sulbactam-based therapy had a similar clinical outcome, but tigecycline group had a lower microbiological eradiation rate.
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http://dx.doi.org/10.1186/s12879-016-1717-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975895PMC
August 2016

Clinical manifestations, course, and outcome of patients with neutralizing anti-interferon-γ autoantibodies and disseminated nontuberculous mycobacterial infections.

Medicine (Baltimore) 2016 Jun;95(25):e3927

Laboratory of Human Immunology and Infectious Diseases, Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan Graduate Institute of Biomedical Science, Chang Gung University, Taoyuan, Taiwan Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan Division of Infectious Diseases, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Division of Infectious Diseases, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Division of Infectious Diseases, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan Department of Infectious Diseases, Buddhist Tzu Chi General Hospital, Hualien, Taiwan Department of Orthopedics, China Medical University Hospital, Taichung, Taiwan Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan Division of Infectious Disease, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Taichung, Taiwan Division of Infectious Diseases, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan Department of Trauma and Emergency Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan Division of Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.

Neutralizing anti-interferon-γ autoantibody (nAIGA)-associated immunodeficiency is an emerging medical issue worldwide. In the present study, we describe and discuss the clinical features and outcomes of patients with nAIGAs and disseminated infections by nontuberculous mycobacteria (dNTM).We thoroughly reviewed the medical records of all patients. Microorganisms and nAIGAs were identified using previously described methods with modifications. All data were calculated and analyzed using SPSS software.Among 46 adult patients with dNTM infections, we identified 45 cases (97.8%) with nAIGAs. The average patient age was 58.6 years, and there was no sex predominance. Cervical lymphadenitis (81.8%) was the most common clinical manifestation. Endocrine disorder was the leading comorbidity (7 cases). Malignancies were found in 4 patients, and all of the malignancies originated from the T-cell/macrophage lineage. More than half of the identifiable isolates were slow-growing NTMs. Twenty-eight (62.2%) and 18 (40.0%) patients had a history of zoster and salmonellosis, respectively. A high proportion of patients with recurrent episodes of NTM infection or a history of zoster and dNTM infection had initial nAIGA titers ≥10 dilution (P < 0.05). Twenty-seven patients (60.0%) required long-term antimycobacterial therapy and had at least 1 episode of recurrent NTM disease. No mortality was related to dNTM infection.In Taiwan, nAIGAs are a recently recognized mechanism of dNTM infection. Long term of antibiotic treatment and adherence to medical advice are necessary to improve the clinical outcome of patients with nAIGAs.
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http://dx.doi.org/10.1097/MD.0000000000003927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998320PMC
June 2016