Cryptococcus tetragattii Meningitis Associated with Travel, Taiwan.

Meningitis caused by Cryptococcus tetragattii fungus is rare and has been found in specific geographic regions. We report a case of meningitis caused by C. tetragattii (molecular type VGIV) in an immunocompetent patient in Taiwan. The patient had traveled to Egypt and was positive for granulocyte-macrophage colony-stimulating factor autoantibody.

Cryptococcus gattii Infection as the Major Clinical Manifestation in Patients with Autoantibodies Against Granulocyte-Macrophage Colony-Stimulating Factor.

PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are a predisposing factor for pulmonary alveolar proteinosis (PAP) and Cryptococcus gattii cryptococcosis. This study aimed to investigate clinical manifestations in anti-GM-CSF Ab-positive patients with C. gattii cryptococcosis and analyze the properties of anti-GM-CSF Abs derived from these patients and patients with PAP. METHODS: Thirty-nine patients diagnosed with cryptococcosis (caused by C. neoformans or C. gattii) and 6 with PAP were enrolled in the present study. Clinical information was obtained from medical records. Blood samples were collected for analysis of autoantibody properties. We also explored the National Health Insurance Research Database (NHIRD) of Taiwan to investigate the epidemiology of cryptococcosis and PAP. RESULTS: High titers of neutralizing anti-GM-CSF Abs were identified in 15 patients with cryptococcosis (15/39, 38.5%). Most anti-GM-CSF Ab-positive cryptococcosis cases had central nervous system (CNS) involvement (14/15, 93.3%). Eleven out of 14 (78.6%) anti-GM-CSF Ab-positive CNS cryptococcosis patients were confirmed to be infected with C. gattii, and PAP did not occur synchronously or metachronously in a single patient from our cohort. Exploration of an association between HLA and anti-GM-CSF Ab positivity or differential properties of autoantibodies from cryptococcosis patients and PAP yielded no significant results. CONCLUSION: Anti-GM-CSF Abs can cause two diseases, C. gattii cryptococcosis and PAP, which seldom occur in the same subject. Current biological evidence regarding the properties of anti-GM-CSF Abs cannot provide clues regarding decisive mechanisms. Further analysis, including more extensive cohort studies and investigations into detailed properties, is mandatory to better understand the pathogenesis of anti-GM-CSF Abs.

Association between angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and community-acquired pneumonia: A nationwide population propensity-score matching study.

BACKGROUND: Few large-scale cohort studies have investigated the association between community-acquired pneumonia and the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). We aimed to study whether using ACEIs or ARBs had protective effects for community-acquired pneumonia. METHODS: This database cohort study was conducted retrospectively in Taiwan. The hypertensive patients were the target population of this study. Patients with ARB use were defined as our first study cohort. The second study cohort comprised patients who used ACEI. Propensity-score matching at 1:1 was used between ARB users and non-ARB users. We recruited 67 944 participants for the ARB study and 58 062 participants for the ACEI study. The same matching was also performed between ACEI users and non-ACEI users. Cox proportional hazard regression was used to analyse the risk of the outcome of viral pneumonia. RESULTS: The hazard ratio of community-acquired pneumonia for ARB users relative to non-ARB users was 0.33. The hazard ratio of community-acquired pneumonia was 0.71 times in ACEI users compared with ACEI nonusers. In stratification analysis, both ARB and ACEI both exhibited a protective effect for community-acquired pneumonia in each age and sex group. In the analysis of the effects of therapy duration, patients using ARB for fewer than 100 days exhibited a greater reduction in the risk of community-acquired pneumonia (adjusted HR = 0.58) compared with the non-ARB cohort. For the ACEI study, patients who used ACEI for 121-450 days were more likely to exhibit reduced risks of community-acquired pneumonia (adjusted HR = 0.5). CONCLUSION: Both ACEI and ARB uses were associated with decreased risk of community-acquired pneumonia infection.

Risk of Viral Infection in Patients Using Either Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers: A Nationwide Population-based Propensity Score Matching Study.

BACKGROUND: We hypothesized that renin-angiotensin system (RAS) blockers have systemic protective effects beyond the respiratory tract and could reduce the risk of viral infections. METHODS: We used the National Health Insurance Research Database and identified 2 study cohorts: the angiotensin receptor blocker (ARB) cohort and angiotensin-converting enzyme inhibitor (ACEI) cohort. Propensity score matching was applied at a 1:1 ratio by all associated variables to select 2 independent control cohorts for the ARB and ACEI cohorts. A Cox proportional hazards model was applied to assess the end outcome of viral infection. RESULTS: The number of ARB and ACEI users was 20 207 and 18 029, respectively. The median age of ARB users and nonusers was 53.7 and 53.8 years, respectively. The median follow-up duration of ARB users and nonusers was 7.96 and 7.08 years; the median follow-up duration of ACEI users and nonusers was 8.70 and 8.98 years, respectively. The incidence rates of viral infections in ARB users and nonusers were 4.95 and 8.59 per 1000 person-years, respectively, and ARB users had a lower risk of viral infection than nonusers (adjusted hazard ratio [aHR], 0.53 [95% confidence interval {CI}, .48-.58]). The incidence rates of viral infections in ACEI users and nonusers were 6.10 per 1000 person-years and 7.72 per 1000 person-years, respectively, and ACEI users had a lower risk of viral infection than nonusers (aHR, 0.81 [95% CI, .74-.88]). CONCLUSIONS: Hypertensive patients using either ARBs or ACEIs exhibit a lower risk of viral infection than nonusers.

Autoantibodies against cytokines: phenocopies of primary immunodeficiencies?

Anti-cytokine autoantibodies may cause immunodeficiency and have been recently recognized as 'autoimmune phenocopies of primary immunodeficiencies' and are found in particular, but not exclusively in adult patients. By blocking the cytokine's biological function, patients with anti-cytokine autoantibodies may present with a similar clinical phenotype as the related inborn genetic disorders. So far, autoantibodies to interferon (IFN)-γ, GM-CSF, to a group of TH-17 cytokines and to IL-6 have been found to be causative or closely associated with susceptibility to infection. This review compares infectious diseases associated with anti-cytokine autoantibodies with primary immunodeficiencies affecting similar cytokines or related pathways.

Disseminated Cryptococcosis Due to Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies in the Absence of Pulmonary Alveolar Proteinosis.

INTRODUCTION: Autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) can cause acquired pulmonary alveolar proteinosis (PAP). Cases of acquired PAP susceptible to typical respiratory pathogens and opportunistic infections have been reported. Anti-GM-CSF autoantibodies have been reported in a few patients with cryptococcal meningitis. This study evaluated the presence of neutralizing anti-GM-CSF autoantibodies in patients without known congenital or acquired immunodeficiency with severe pulmonary or extrapulmonary cryptococcal infection but without PAP. METHODS: We took a clinical history and performed an immunologic evaluation and screening of anti-cytokine autoantibodies in patients with cryptococcal meningitis. The impact of autoantibodies to GM-CSF on immune function was assessed by intracellular staining of GM-CSF-induced STAT5 phosphorylation and MIP-1α production in normal peripheral blood mononuclear cells incubated with plasma from patients or normal control subjects. RESULTS: Neutralizing anti-GM-CSF autoantibodies were identified in four patients with disseminated cryptococcosis, none of whom exhibited PAP. Plasma from patients blocked GM-CSF signaling and inhibited STAT5 phosphorylation and production of MIP-1α. One patient died of disseminated cryptococcosis involving the central nervous system, which was associated with defective GM-CSF activity. CONCLUSIONS: Anti-GM-CSF autoantibodies increase susceptibility to cryptococcal infection in adults without PAP. Cryptococcal central nervous system infection associated with anti-GM-CSF autoantibodies could result in neurological sequelae or be life-threatening. Therefore, timely detection of neutralizing anti-GM-CSF autoantibodies and development of an effective therapy are necessary to prevent deterioration of cryptococcal infection in these patients.

Anti-IFN-γ autoantibodies in adults with disseminated nontuberculous mycobacterial infections are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster virus infection.

Adult patients with disseminated nontuberculous mycobacterial (dNTM) infections usually have severe immune system defects. Recently, several studies have shown that anti-IFN-γ autoantibodies may play an important role in the pathogenicity of dNTM infections. A considerable proportion of reported cases of anti-IFN-γ autoantibodies show either clinical or laboratory evidence of autoimmune disease. In the present study, we identified 19 formerly healthy adults who later developed dNTM infections, of whom 17 were further investigated immunologically. High-titer anti-IFN-γ autoantibodies capable of inhibiting IL-12 production in vitro were found in the plasma of all of these patients. In addition to dNTM infection, 35% and 71% of our patients also suffered from salmonellosis and herpes zoster, respectively. This observation suggests that IFN-γ may be crucial in controlling salmonella infection and reactivating latent varicella-zoster virus infection in humans. 2 HLA alleles, DRB1*16:02 DQB1*05:02 (odds ratio 8.68; 95% confidence interval, 3.47-21.90; P = 1.1 × 10(-6); Pc = 3.08 × 10(-5) and odds ratio 7.16; 95% confidence interval, 3.02-17.05; P = 1 × 10(-7); Pc = 1.4 × 10(-6), respectively), were found in 82% (14 of 17) of our patients. In conclusion, our data suggest that anti-IFN-γ autoantibodies may play a critical role in the pathogenesis of dNTM infections and reactivation of latent varicella-zoster virus infection and are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02.

Yeast oropharyngeal colonization in human immunodeficiency virus-infected patients in central taiwan.

A prospective, cross-sectional study was conducted at a medical center in central Taiwan to understand the prevalence, associated factors, and microbiologic features for oropharyngeal yeast colonization in human immunodeficiency virus-infected outpatients. Oral yeast colonization was detected in 127 (45 %) patients, including 21 (16.5 %) colonized by more than one species. Of the 154 isolates, Candida albicans was the most common species (114, 74 %), followed by Candida dubliniensis (10, 6.5 %), Candida glabrata (10, 6.5 %), Candida tropicalis (7, 4.5 %), and 13 others. We found that receiving antituberculous drug (p = 0.046) or atazanavir (p = 0.045) was two predictors for patients colonized by non-C. albicans species (p = 0.005) and risking mixed yeast colonization (p = 0.009). Even though our data showed that clinical antifungal drugs remained effective in vitro against the colonizing yeasts, the increased mixed yeast colonization indicates a potential issue for controlling mixed infections in hospital settings.

Gut microbiome profiles and associated metabolic pathways in patients of adult-onset immunodeficiency with anti-interferon-gamma autoantibodies.

Autoantibodies against interferon-gamma (AutoAbs-IFN-γ) can cause the immunodeficiency condition following various opportunistic infections. Gut microbiota can affect the human immune system in many ways. Many studies have shown that gut dysbiosis was associated with some immune diseases, such as autoimmune diseases and human immunodeficiency virus (HIV) infection, while its relationship at anti-IFN-γ AAbs remains unknown. We aimed to identify the anti-IFN-γ AAbs specific microbiome and the possible association with immunodeficiency. We profiled fecal microbiome for two cohorts of forty subjects, including seven patients with anti-IFN-γ AAbs and 33 individuals with competent immune. The study shows that patients with anti-IFN-γ AAbs have characterized the gut microbiome and have lower alpha diversity indexes than healthy controls (HC). There are significant differences in the microbiome structure at both the family and genera level between the two cohorts. The anti-IFN-γ AAbs cohort featured some microbiome such as Clostridium, including the possible opportunistic pathogen and fewer genera including Bacteroides, Ruminococcus, and Faecalibacterium, some of them with possible immune-related genera. The PICRUSt2 pathway demonstrated the decreased abundance of some immune-related pathways and one potential pathway related to the immune alternations in the anti- IFN-γ AAbs cohort. This was the first study to examine the gut microbiome characteristics in patients with anti-IFN-γ AAbs. It could be involved in the pathogenesis of anti-IFN-γ AAbs and contribute to the derived immune condition in this disease. This could lead to new strategies for treating and preventing patients suffering from this disease.

Definite therapy of mixed infection alleviates refractory dilemma of adult chronic suppurative otitis media.

The characteristics, risk factors, microbial distributions and effective treatment regimens for Chronic suppurative otitis media (CSOM) patients intractable to empirical therapy were analyzed. Adult CSOM patients of China Medical University Hospital from 2018 to 2020 were included. Subjects of refractory and non-refractory groups were investigated for characteristics of age, sex, nation, comorbidities, otomycosis, and associated complications. Risk factors, microbiology distributions, and treatment regimens were analyzed. Twenty-six refractory patients (55.0 ± 17.7 years) and 66 non-refractory patients (54.1 ± 13.7 years) were studied. A significantly higher rate of otomycosis and CSOM complications was observed in refractory group than in non-refractory one (73.1% vs. 36.4%; p = 0.002; 57.7% vs. 10.6%, p < 0.001, respectively). Multivariate analysis revealed atopic diathesis (p = 0.048), otomycosis (p = 0.003) and CSOM complications (p < 0.001) were risk factors of refractory CSOM. Coagulase-negative staphylococci (CoNS) and methicillin-resistant Staphylococcus aureus (MRSA) were the prevailing pathogens. Patients of refractory group tented to have higher rates of mixed infection (42.9%% vs. 23.7%) and significantly more included fungal pathogen (19.0% vs. 2.6%; p = 0.049) than those of non-refractory cohort. Topical treatment of fungus significantly improved outcome of refractory CSOM. Atopic diathesis, otomycosis, and CSOM-associated complications were risk factors of refractory CSOM. Systemic and local treatment to possible drug-resistant pathogens, likely CoNS and fungus, possible improves recalcitrant CSOM. Correspondingly, early identification of CSOM complications, routine culture and susceptibility testing and treatment of resistant bacteria and fungus are key elements to the successful management of adult CSOM.

Mesenchymal stem cell therapy on top of triple therapy with remdesivir, dexamethasone, and tocilizumab improves PaO2/FiO2 in severe COVID-19 pneumonia.

Background: Despite patients with severe coronavirus disease (COVID-19) receiving standard triple therapy, including steroids, antiviral agents, and anticytokine therapy, health condition of certain patients continue to deteriorate. In Taiwan, the COVID-19 mortality has been high since the emergence of previous variants of this disease (such as alpha, beta, or delta). We aimed to evaluate whether adjunctive infusion of human umbilical cord mesenchymal stem cells (MSCs) (hUC-MSCs) on top of dexamethasone, remdesivir, and tocilizumab improves pulmonary oxygenation and suppresses inflammatory cytokines in patients with severe COVID-19. Methods: Hospitalized patients with severe or critical COVID-19 pneumonia under standard triple therapy were separated into adjuvant hUC-MSC and non-hUC-MSC groups to compare the changes in the arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio and biological variables. Results: Four out of eight patients with severe or critical COVID-19 received either one (n = 2) or two (n = 2) doses of intravenous infusions of hUC-MSCs using a uniform cell dose of 1.0 × 108. Both high-sensitivity C-reactive protein (hs-CRP) level and monocyte distribution width (MDW) were significantly reduced, with a reduction in the levels of interleukin (IL)-6, IL-13, IL-12p70 and vascular endothelial growth factor following hUC-MSC transplantation. The PaO2/FiO2 ratio increased from 83.68 (64.34-126.75) to 227.50 (185.25-237.50) and then 349.56 (293.03-367.92) within 7 days after hUC-MSC infusion (P < 0.001), while the change of PaO2/FiO2 ratio was insignificant in non-hUC-MSC patients (admission day: 165.00 [102.50-237.61]; day 3: 100.00 [72.00-232.68]; day 7: 250.00 [71.00-251.43], P = 0.923). Conclusion: Transplantation of hUC-MSCs as adjunctive therapy improves pulmonary oxygenation in patients with severe or critical COVID-19. The beneficial effects of hUC-MSCs were presumably mediated by the mitigation of inflammatory cytokines, characterized by the reduction in both hs-CRP and MDW.

Pathogenic autoantibodies to IFN-γ act through the impedance of receptor assembly and Fc-mediated response.

Anti-interferon (IFN)-γ autoantibodies (AIGAs) are a pathogenic factor in late-onset immunodeficiency with disseminated mycobacterial and other opportunistic infections. AIGAs block IFN-γ function, but their effects on IFN-γ signaling are unknown. Using a single-cell capture method, we isolated 19 IFN-γ-reactive monoclonal antibodies (mAbs) from patients with AIGAs. All displayed high-affinity (KD < 10-9 M) binding to IFN-γ, but only eight neutralized IFN-γ-STAT1 signaling and HLA-DR expression. Signal blockade and binding affinity were correlated and attributed to somatic hypermutations. Cross-competition assays identified three nonoverlapping binding sites (I-III) for AIGAs on IFN-γ. We found that site I mAb neutralized IFN-γ by blocking its binding to IFN-γR1. Site II and III mAbs bound the receptor-bound IFN-γ on the cell surface, abolishing IFN-γR1-IFN-γR2 heterodimerization and preventing downstream signaling. Site III mAbs mediated antibody-dependent cellular cytotoxicity, probably through antibody-IFN-γ complexes on cells. Pathogenic AIGAs underlie mycobacterial infections by the dual blockade of IFN-γ signaling and by eliminating IFN-γ-responsive cells.

Anti-interferon-γ autoantibody-associated immunodeficiency.

Anticytokine autoantibodies are an emerging disease etiology, through the disturbance of physiological functions of cognate cytokines. Anti-interferon (IFN)-γ autoantibodies (AIGAs) were first identified in patients with severe mycobacterial infections, and were considered to be an autoimmune phenocopy of inborn genetic errors of the IL-12/IFN-γ axis. More than 600 reported cases, most originating from Southeast Asia, have been diagnosed over the last decade. Specific HLA class II molecules are associated with these autoantibodies, which provide a genetic basis for the high prevalence of this immunodeficiency syndrome in certain ethnic groups. Salmonellosis and herpes zoster reactivation are observed in more than half the patients with AIGAs. Moreover, AIGAs have been shown to underlie severe Taralomyce marneffei infection in HIV-negative patients. AIGAs may, thus, be considered a new form of late-onset immunodeficiency conferring a predisposition not only to severe mycobacterial, but also to some bacterial and fungal infections.

Trend and Predictors of Short-term Mortality of Adult Bacteremia at Emergency Departments: A 14-Year Cohort Study of 14 625 Patients.

BACKGROUND: Bacteremia is a life-threatening condition with a high mortality rate in critical care and emergency settings. The current study investigated the trend of mortality and developed predictive models of mortality for adults with bacteremia at emergency departments (EDs). METHODS: We conducted a retrospective cohort study of adults with bacteremia at the ED of China Medical University Hospital. Patient data were obtained from the Clinical Research Data Repository, and mortality information was obtained from the National Death Registry. We developed a new model to predict 7-day mortality in the derivation population and compared the model performance of the new model with Pitt Bacteremia Score (PBS) and Bloodstream Infection Mortality Risk Score (BSIMRS) in the validation population. RESULTS: We identified 14625 adult patients with first-time bacteremia at the ED, of whom 8.4% died within 7 days. From 2003 to 2016, both the cumulative incidence and 7-day mortality rate of bacteremia decreased significantly. The ED bacteremia mortality (ED-BM) model included PBS parameters, age, infection source, baseline steroid use, and biochemical profiles (estimated glomerular filtration rate, platelet, blood urea nitrogen, potassium, and hemoglobin) for predicting 7-day mortality. The discrimination performance of the ED-BM model (area under curve [AUC], 0.903) was significantly better than that of PBS (AUC, 0.848) or BSIMRS (AUC, 0.885). CONCLUSIONS: Although the cumulative incidence and mortality of ED bacteremia decreased, its mortality burden remains critical. The proposed ED-BM model had significantly better model performance than other scoring systems in predicting short-term mortality for adult patients with bacteremia at EDs.

Risk factors of tuberculosis after liver transplant in a tertiary care hospital.

BACKGROUND: Tuberculosis (TB) is a serious opportunistic infection in liver transplant (LT) recipients with a high rate of morbidity and mortality. This study aims to clarify the frequency and risk factors for tuberculosis in LT recipients. METHODS: A total of 884 LT recipients were investigated retrospectively at China Medical University Hospital, Taichung, Taiwan. We performed a case-control study (1:2) to investigate the potential risk factors and disease onset of TB after LT. RESULTS: Among the 884 LT recipients, 25 of TB cases (2.8%) were reported from 2009 to 2016. The overall incidence of TB was 744 cases per 100,000 patient-year, which was 18-fold higher than the general population in Taiwan. The median time to develop TB after liver transplant was 20 months. Of the TB cases, 15 were pulmonary TB and 10 were extra-pulmonary TB. Five cases of those extra-pulmonary TB occurred in the first post-transplant year. Overall five-year survival rate was 63.3%. Multivariate analyses identified apical fibrotic change in pre-transplant computed tomographic (CT) finding and the exposure to mammalian target of rapamycin (mTOR) inhibitors before TB event as independent risk factors for TB development (Odd ratio (OR) 10.79, 95% confidence interval (CI), 1.73-67.49, p = 0.01; OR 3.847, 95% CI 0.80-18.51, P = 0.09, respectively). CONCLUSION: TB incidence in LT recipients is high in this study. Among those post-transplant recipients with long-term immunosuppression, abnormal CT finding and exposure to mTOR inhibitors before liver transplant might be the risk factors for TB.

Electronic medical record-based deep data cleaning and phenotyping improve the diagnostic validity and mortality assessment of infective endocarditis: medical big data initiative of CMUH.

BACKGROUND: International Classification of Diseases (ICD) code-based claims databases are often used to study infective endocarditis (IE). However, the quality of ICD coding can influence the reliability of IE research. The impact of complementing the ICD-only approach with data extracted from electronic medical records (EMRs) has yet to be explored. METHODS: We selected the information of adult patients with discharge ICD codes for IE (ICD-9: 421, 112.81, 036.42, 098.84, 115.04, 115.14, 115.94, 424.9; ICD-10: I33, I38, I39) during 2005-2016 in China Medical University Hospital. Data extraction was conducted on the basis of the modified Duke criteria to establish a reference group comprising patients with definite or possible IE. Clinical characteristics and in-hospital mortality were compared between ICD-identified and Duke-confirmed cases. The positive predictive value (PPV) was used to quantify the IE identification performance of various phenotyping algorithms. RESULTS: A total of 593 patients with discharge ICD codes for IE were identified, only 56.7% met the modified Duke criteria. The crude in-hospital mortality for Duke-confirmed and Duke-rejected IE were 24.4% and 8.2%, respectively. The adjusted in-hospital mortality for ICD-identified IE was lower than that for Duke-confirmed IE by a difference of 5.1%. The best PPV was achieved (0.90, 95% CI 0.86-0.93) when major components of the Duke criteria (positive blood culture and vegetation) were integrated with ICD codes. CONCLUSION: Integrating EMR data can considerably improve the accuracy of ICD-only approaches in phenotyping IE, which can improve the validity of EMR-based studies and their applications, including real-time surveillance and clinical decision support.

Younger adults with mild-to-moderate COVID-19 exhibited more prevalent olfactory dysfunction in Taiwan.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is rapidly transmitted from person to person, causing global pandemic since December 2019. Instantly detecting COVID-19 is crucial for epidemic prevention. In this study, olfactory dysfunction is a significant symptom in mild to moderate COVID-19 patients but relatively rare in other respiratory viral infections. The Taiwan smell identification test (TWSIT) is a speedy and inexpensive option for accurately distinguishing anosmia that also quantifies the degree of anosmia. Using TWSIT in the outpatient clinic for early identifying the patients with mild to moderate COVID-19 can be promising. METHODS: Nineteen patients confirmed COVID-19 in central Taiwan were collected and divided into two groups: olfactory dysfunction and non-olfactory dysfunction. Demographic characteristics, laboratory findings, and the results of the olfactory test were compared between these two groups. FINDINGS: Thirteen (68.4%) of the 19 patients had olfactory dysfunction. The patients with olfactory dysfunction were younger than those without this symptom. The statistical difference in age distribution was significant between these two groups (IQR: 25.5-35.5 vs. IQR: 32.5-60.3; p-value: 0.012). There was no significant difference in gender, smoking history, comorbidities, travel history, respiratory tract infection symptoms, and laboratory findings between these two groups. CONCLUSION: This study demonstrated that young adults were prone to develop olfactory dysfunctions. In the flu season, olfactory dysfunction is considered a specific screening criterion for early detecting COVID-19 in the community. TWSIT can serve as a decent test for quantifying and qualifying olfactory dysfunction.

Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CO-V-2), was first reported in Wuhan, Hubei province, China has now rapidly spread over 50 countries. For the prevention and control of infection, Taiwan Centers for Disease Control initiated testing of SARS-CoV-2 on January 24th 2020 for persons suspected with this disease. Until February 28th, 43 flu-like symptomatic patients were screened in China Medical University Hospital. METHODS: Two patients were confirmed positive for SARS-CoV-2 infection by rRT-PCR as COVID-19 patients A and B. Causative pathogens for included patients were detected using FilmArray™ Respiratory Panel. We retrospectively analyzed the clinical presentations, laboratory data, radiologic findings, and travel and exposure contact histories, of the COVID-19 patients in comparison to those with other respiratory infections. RESULTS: Through contact with Taiwan No. 19 case patient on 27th January, COVID-19 patients A and B were infected. Both patients had no identified comorbidities and developed mild illness with temporal fever, persistent cough, and lung interstitial infiltrates. Owing to the persistence of positive SARS-CoV-2 in respiratory specimen, the two COVID-19 patients are still in the isolation rooms despite recovery until 10th of March. The results of FilmArrayTM Respiratory Panel revealed 22 of the 41 non-COVID-19 patients were infected by particular pathogens. In general, seasonal respiratory pathogens are more prevalent than SARS-CoV-2 in symptomatic patients in non- COVID-19 endemic area during the flu season. Since all patients shared similar clinical and laboratory findings, expanded surveillance of detailed exposure history for suspected patients and application of rapid detection tools are highly recommended.

Long-Term Surveillance of Antibiotic Prescriptions and the Prevalence of Antimicrobial Resistance in Non-Fermenting Gram-Negative Bacilli.

The increasing emergence of multidrug-resistant (MDR) bacteria has been recognized as a public health threat worldwide. Hospitalized patients and outpatients are commonly infected by non-fermenting Gram-negative bacilli (NFGNB), particularly the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ACB) and Pseudomonas aeruginosa. Antimicrobial agents are critical for treating the nosocomial infections caused by NFGNB. The aim of this study was to assess antimicrobial resistance and the use of antimicrobial agents. The bacterial isolates of 638,152 specimens from both inpatients and outpatients, retrieved from 2001 to 2008 at a medical center in central Taiwan, were examined for their susceptibility to various antimicrobial agents, including cefepime, imipenem, ciprofloxacin, gentamicin, amikacin, meropenem, and levofloxacin. Administrated prescriptions of the monitored antibiotics were analyzed using the Taiwan National Health Insurance Research Database (NHIRD). Our results show that the defined daily doses (DDDs) for cefepime, imipenem, and ciprofloxacin increased with time, and a trend toward reduced antimicrobial sensitivities of both ACB and P. aeruginosa was noticeable. In conclusion, the antimicrobial sensitivities of ACB and P. aeruginosa were reduced with the increased use of antibiotics. Continuous surveillance of antibiotic prescriptions and the prevalence of emerging resistance in nosocomial infections is warranted.