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Background/purpose Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan. Methods A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed. Results Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid. Conclusion Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan.

Background It is unclear about the impact of recreational drug use on the adherence, drug–drug interaction and the occurrence of sexual transmitted diseases (STDs) among people living with HIV. Material and methods A retrospective study was conducted between Dec 2016, and July 2018 to assess the clinical impact of recreational drug consumption in people living with HIV with antiretroviral therapy. We collected data of the demographics, recreational drug use, laboratory results and STDs diagnoses. Potential drug–drug interactions were checked with reference databases. The association between recreational drug use and STDs, HIV viral load suppression and drug interactions were evaluated. Results A total of 462 participants were enrolled, included 384 recreational drug users and 78 non-recreational drug users. Younger age (adjusted odds ratio [aOR], 0.94; 95% CI: 0.91–0.98; p = 0.001), longer HIV infection period (aOR, 1.11; 95% CI: 1.03–1.20; p = 0.009) and poor antiretroviral drug adherence (1–2 pills missing per month: aOR, 6.82; 95% CI: 3.50–13.27; p 2 pills missing per month: aOR, 3.50; 95% CI: 1.28–9.61; p = 0.015) were factors associated with recreational drug use. Methamphetamine and nitrites were two most common recreational drugs. Recreational drug use was significantly associated with STDs in one-year follow-up period (aOR, 2.43; 95% CI: 1.11–5.32; p = 0.027) but was not significantly associated with unsuppressed viral load, though a trend was observed (OR, 2.23; 95% CI: 0.92–5.37; p = 0.074). Potential interactions with recreational drugs included 33.1% antiretroviral drugs and 31.3% medications for comorbidities. Conclusion Recreational drug was associated with STDs. A great proportion of the patients consuming recreational drugs had potential interactions with antiretroviral drugs and medications for comorbidities. The association of recreational drug use and unsuppressed viral load warrants further investigation.

Objectives The aim of this study was to investigate the trends in serotypes and in vitro antimicrobial susceptibility of Streptococcus pneumoniae causing adult invasive pneumococcal disease (IPD) to dalbavancin, telavancin, tedizolid, eravacycline, omadacycline and other comparator antibiotics from 2017–2020 following implementation of the 13-valent pneumococcal conjugate vaccine (PCV-13) and during the COVID-19 (coronavirus disease 2019) pandemic. Methods During the study period, 237 S. pneumoniae isolates were collected from non-duplicate patients, covering 15.0% of IPD cases in Taiwan. Antimicrobial susceptibility testing was performed using a Sensititre® system. A latex agglutination method (ImmuLex™ Pneumotest Kit) was used to determine serotypes. Results Susceptibility rates were high for vancomycin (100%), teicoplanin (100%) and linezolid (100%), followed by ceftaroline (non-meningitis) (98.3%), moxifloxacin (94.9%) and quinupristin/dalfopristin (89.9%). MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline and omadacycline were generally low. Non-vaccine serotype 23A was the leading cause of IPD across the adult age range. Isolates of serotype 15B were slightly fewer than those of PCV-13 serotypes in patients aged ≥65 years. The overall case fatality rate was 15.2% (36/237) but was especially high for non-PCV-13 serotype 15B (21.4%; 3/14). Vaccine coverage was 44.7% for PCV-13 and 49.4% for the 23-valent pneumococcal polysaccharide vaccine (PPSV-23), but was 57% for both PCV-13 and PPSV-23. Conclusion The incidence of IPD was stationary after PCV-13 introduction and only dramatically decreased in the COVID-19 pandemic in 2020. The MIC50 and MIC90 values of dalbavancin, telavancin, tedizolid, eravacycline, omadacycline were generally low for S. pneumoniae causing adult IPD.

Background/purpose: Tuberculosis (TB) in the elderly population remains a major challenge in areas with intermediate disease burden like Taiwan. Despite the increasing burden and high risks of TB in the elderly population, particularly those living in long-term care facilities (LTCFs), diagnostic testing for latent tuberculosis infection (LTBI) has not been carefully evaluated in this group. This study aimed to investigate the prevalence and predictors of LTBI in older adults living in LTCFs. Methods: Older adults living in seven LTCFs in Taiwan were prospectively enrolled between January and July 2017. Interferon-gamma release assay (IGRA) through QuantiFERON-TB Gold In-tube was used to determine presence of LTBI. Predictors for LTBI were analyzed. Results: A total of 258 participants were enrolled, including 240 older residents (mean age, 81.6 years; male, 51.2%) and 18 employees (mean age, 64.8 years; male, 22.2%). The proportion of independent status in ambulation assessments significantly declined with aging (p

Background Dengue is an arboviral disease caused by dengue virus. Symptomatic dengue infection causes a wide range of clinical manifestations, from mild dengue fever (DF) to potentially fatal disease, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). We conducted a literature review to analyze the risks of DHF and current perspectives for DHF prevention and control. Methods According to the PRISMA guidelines, the references were selected from PubMed, Web of Science and Google Scholar database using search strings containing a combination of terms that included dengue hemorrhagic fever, pathogenesis, prevention and control. Quality of references were evaluated by independent reviewers. Results DHF was first reported in the Philippines in 1953 and further transmitted to the countries in the region of South-East Asia and Western Pacific. Plasma leakages is the main pathophysiological hallmark that distinguishes DHF from DF. Severe plasma leakage can result in hypovolemic shock. Various factors are thought to impact disease presentation and severity. Virus virulence, preexisting dengue antibodies, immune dysregulation, lipid change and host genetic susceptibility are factors reported to be correlated with the development of DHF. However, the exact reasons and mechanisms that triggers DHF remains controversial. Currently, no specific drugs and licensed vaccines are available to treat dengue disease in any of its clinical presentations. Conclusion This study concludes that antibody-dependent enhancement, cytokine dysregulation and variation of lipid profiles are correlated with DHF occurrence. Prompt diagnosis, appropriate treatment, active and continuous surveillance of cases and vectors are the essential determinants for dengue prevention and control.

Background Although C-reactive protein (CRP) and procalcitonin (PCT) are widely used inflammatory markers for infectious diseases, their role and potential application for rickettsioses were rarely studied. Methods A retrospective chart review and serological study were conducted in patients with rickettsioses. The clinical presentations, characteristics, laboratory data, and treatment responses were recorded and their associations with CRP and PCT values were analyzed. Results A total of 189 cases of rickettsioses, including 115 cases of acute Q fever (60.8%), 55 cases of scrub typhus (29.1%), and 19 cases of murine typhus (10.1%) were investigated. Both CRP and PCT values increased in the acute phase and declined in the convalescent phase. In the acute phase, mean CRP and PCT values were 78.2 ± 63.7 mg/L and 1.05 ± 1.40 ng/mL, respectively. Percentages of patients falling under different cut-off values of CRP and PCT were calculated systematically. Only 10.8% of CRP was > 150 mg/L and 14.2% of PCT was > 2.0 ng/mL. Patients with delayed responses to doxycycline treatment (> 3 days from treatment to defervescence) had significantly higher CRP values (102.7 ± 77.1 vs. 72.2 ± 58.2 mg/L, p = 0.041) and more PCT > 1.0 ng/ml (48.4% vs. 26.0%, p = 0.019) in the acute phase; higher CRP values (19.1 ± 37.4 vs. 3.6 ± 13.1 mg/L, p = 0.049) and more PCT > 0.5 ng/ml (19.2% vs. 1.4%, p = 0.005) in the convalescent phase. Correlation analysis was conducted for patients with acute Q fever. CRP and PCT values were positively correlated to each other, and both markers also had a positive correlation with serum aspartate transaminase values. Both CRP and PCT values and white blood cell counts were positively correlated to the days needed from doxycycline treatment to defervescence. Conclusion CRP and PCT values might be useful in clinical investigations for patients with suspected rickettsioses and in predicting the response to doxycycline treatment for rickettsioses.

Several studies have demonstrated that malnutrition is a negative prognostic factor for clinical outcomes. However, there is limited evidence for the effect of malnutrition on clinical outcomes in patients with candidemia. We investigated the relationship between malnutrition and all-cause 28-day mortality among patients with non-albicans candidemia. Between July 2011 and June 2014, all adult patients with non-albicans candidemia, including C. tropicalis, C. glabrata, C. parapsilosis and so on, were enrolled. The Malnutrition Universal Screening Tool (MUST) scores were used to determine the patients’ nutritional status before the onset of candidemia. A total of 378 patients were enrolled, 43.4% developed septic shock and 57.1% had a high risk of malnutrition (MUST ≥ 2). The all-cause 28-day mortality rate was 40.7%. The Cox proportional hazards model revealed that C. tropicalis (HR, 2.01, 95% CI, 1.24–3.26, p = 0.005), Charlson comorbidity index (HR, 1.10, 95% CI, 1.03–1.18, p = 0.007), Foley catheter use (HR, 1.68, 95% CI, 1.21–1.35, p = 0.002), concomitant bacterial infections (HR, 1.55, 95% CI, 1.11–2.17, p = 0.010), low platelet count (HR, 3.81, 95% CI, 2.45–5.91, p &lt, 0.001), not receiving antifungals initially (HR, 4.73, 95% CI, 3.07–7.29, 0.001), and MUST ≥ 2 (HR, 1.54, 95% CI, 1.09–2.17, p = 0.014) were independently associated with all-cause 28-day mortality. A simple screening tool for nutritional assessment should be used for patients with non-albicans candidemia to detect early clinical deterioration, and a tailored nutritional care plan should be established for malnourished individuals, to improve their clinical outcomes.

ObjectivesThis study aimed to investigate the relationship between cardiovascular mortality in elderly Asians and decline in renal function.DesignA retrospective cohort study.SettingCommunity-based health examination database from Taipei city.ParticipantsAt the beginning, the database included 315 045 health check-up visits of 97 803 elderly persons aged ≥65 years old from 2005 to 2012. After excluding missing values and outliers, there were 64 732 elderly persons with at least two visits retained for further analyses.Primary outcome measuresKidney function indicators include estimated glomerular filtration rate (eGFR) and urine protein, and rapid decline in eGFR was defined as slope ≤ −5 mL/min/1.73 m2 per year. The endpoint outcome was defined as the cardiovascular deaths registered in the death registry encoded by the International Classification of Diseases. We applied a Cox proportional hazards model to analyse the association between renal function and cardiovascular mortality.ResultsIn this study, we found 1264 elderly persons died from cardiovascular diseases, for whom the data included 4055 previous health check-up visits. We observed significant and independent associations of eGFR 2 (HR (95% CI) of 60>eGFR≥45 and eGFRConclusionsRenal function and rapid decline in renal function are independent risk factors for cardiovascular mortality in the elderly.

Dengue virus (DENV) is a global health threat causing about half of the worldwide population to be at risk of infection, especially the people living in tropical and subtropical area. Although the dengue disease caused by dengue virus (DENV) is asymptomatic and self-limiting in most people with first infection, increased severe dengue symptoms may be observed in people with heterotypic secondary DENV infection. Since there is a lack of specific antiviral medication, the development of dengue vaccines is critical in the prevention and control this disease. Several targets and strategies in the development of dengue vaccine have been demonstrated. Currently, Dengvaxia, a live-attenuated chimeric yellow-fever/tetravalent dengue vaccine (CYD-TDV) developed by Sanofi Pasteur, has been licensed and approved for clinical use in some countries. However, this vaccine has demonstrated low efficacy in children and dengue-naïve individuals and also increases the risk of severe dengue in young vaccinated recipients. Accordingly, many novel strategies for the dengue vaccine are under investigation and development. Here, we conducted a systemic literature review according to PRISMA guidelines to give a concise overview of various aspects of the vaccine development process against DENVs, mainly targeting five potential strategies including live attenuated vaccine, inactivated virus vaccine, recombinant subunit vaccine, viral-vector vaccine, and DNA vaccine. This study offers the comprehensive view of updated information and current progression of immunogen selection as well as strategies of vaccine development against DENVs.

Yu-Ting Tseng,1,2 Pei-Yun Chou,1 Ming-Hong Tai,2,3 Chia-Yen Dai,4– 6 Susan Shin-Jung Lee,1,7 Yao-Shen Chen,1,7 Hung-Chin Tsai,1,3,7,8,* Yen-Hsu Chen2,6,9– 13,* 1Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; 4Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 5Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 6School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; 8Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan; 9Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Sepsis Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 11Center of Tropical Medicine and Infectious Diseases, Kaohsiung Medical University, Kaohsiung, Taiwan; 12Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan; 13Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Hung-Chin TsaiDivision of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, TaiwanEmail hctsai1011@yahoo.com.twYen-Hsu ChenGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanEmail infchen@gmail.comBackground: The Jarisch–Herxheimer reaction (JHR) is an inflammatory reaction that can occur after treatment for syphilis. The mechanism of JHR is unknown. The level of C-reactive protein (CRP) increases during infection and inflammation. We hypothesized that CRP may be involved in the JHR in syphilitic patients at initial syphilis infection and also through interactions with benzathine penicillin-induced phagocytosis.Methods: This prospective cohort study enrolled syphilitic adult patients with/without JHR between July 2018 and October 2020. Serum samples before and after the administration of the first dose of benzathine penicillin were obtained. The serum level of CRP was determined by ELISA. The Kruskal–Wallis test was used to compare the levels of CRP in different groups, and the Wilcoxon signed-rank test was used to compare changes in CRP before and after benzathine penicillin treatment.Results: Twenty-nine syphilitic patients and three control groups (10 men who have sex with men (MSM) taking pre-exposure prophylaxis, 10 HIV-infected patients without syphilis, and 12 HIV-infected patients with previous syphilis) were enrolled. All 29 syphilitic patients were MSM, and 21 patients (72%) were infected with HIV. Overall, 41% (12/29) of the patients developed the JHR. The active syphilis groups had significantly higher serum levels of CRP (median 11,761 ng/mL, IQR 2986– 19,061 ng/mL). There were no significant differences in the serum levels of CRP before or after benzathine penicillin treatment. The 12 patients with the JHR had significantly higher CRP levels before benzathine penicillin treatment (16,262 ng/mL [IQR 12,033– 26,150 ng/mL] vs 3489 ng/mL [IQR 924– 160,640] ng/mL, p = 0.0059, 95% CI 4002– 17,098 ng/mL, area under the curve 0.799, 95% CI 0.632– 0.966, sensitivity 1, specificity 0.647, with a CRP cut-off value of 4569.32 ng/mL).Conclusion: A high baseline CRP level can predict the occurrence of the JHR in syphilitic patients treated with benzathine penicillin.Keywords: C-reactive protein, Jarisch-Herxheimer reaction, syphilis

Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption.We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption. All the participants had undetectable plasma viremia (20 copies of HIV RNA per milliliter) at the screening visit. After discontinuation of ART, participants received eight intravenous infusions of UB-421, at a dose of either 10 mg per kilogram of body weight every week (Cohort 1) or 25 mg per kilogram every 2 weeks (Cohort 2). The primary outcome was the time to viral rebound (≥400 copies per milliliter).A total of 29 participants were enrolled, 14 in Cohort 1 and 15 in Cohort 2. Administration of UB-421 maintained virologic suppression (20 copies per milliliter) in all the participants (94.5% of measurements at study visits 2 through 9) during analytic treatment interruption, with intermittent viral blips (range, 21 to 142 copies per milliliter) observed in 8 participants (28%). No study participants had plasma viral rebound to more than 400 copies per milliliter. CD4+ T-cell counts remained stable throughout the duration of the study. Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash. A decrease in the population of CD4+ regulatory T cells was observed during UB-421 monotherapy.UB-421 maintained virologic suppression (during the 8 to 16 weeks of study) in participants in the absence of ART. One participant discontinued therapy owing to a rash. (Funded by United Biomedical and others; ClinicalTrials.gov number, NCT02369146.).

Background/purpose: The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear. Methods: We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18–64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002–2011. Results: Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01–0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33–9.99). Conclusion: The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications. Keywords: Elderly, Scrub typhus, Acute Q fever, Murine typhus, Complications

The consequences of once-weekly rifapentine plus isoniazid for 3 months (3HP) against latent tuberculosis infections in hemodialysis patients have not been studied before. This is the first study to evaluate the safety and tolerability of 3HP in this population and revealed a completion rate of 65.4%. The therapy was not associated with hepatotoxicity, but with high rates of adverse events (69.2%). Keywords: Rifapentine, 3HP, Latent tuberculosis, LTBI, Hemodialysis

Purpose In 2012, the Clinical and Laboratory Standards Institute (CLSI) revised its breakpoints for drugs and species because of the increase in non-albicans Candida infections and their drug resistance. Following global trends, the non-albicans candidemia resistance rate has increased in Taiwan as well. To update the antifungal susceptibility of non-albicans candidemia isolates, we conducted a multicenter study using the revised break points. Patients and methods Patients with non-albicans candidemia infections were identified at five tertiary hospitals in Taiwan from July 1, 2011, to June 30, 2014. The broth microdilution method using a Sensititre YeastOne system was performed for the determination of minimum inhibitory concentration (MIC). The susceptibility was interpreted based on the guidelines of the CLSI (CLSI M27-S4 and M27-S3). Results Candida tropicalis was the predominant non-albicans candidemia pathogen (42.4%), and it showed increased fluconazole non-susceptibility (36.3%) when compared to the results from previous studies. In particular, C. tropicalis showed high cross-resistance to azole agents. C. tropicalis isolates that were found to be resistant to fluconazole also showed increased resistance to voriconazole (82.2%) and posaconazole (100%). The increased non-susceptibility of Candida glabrata to multiple antifungal agents, based on the revised break points, resulted from an increase in dose-dependent susceptibility (94.4%) rather than from an increase in resistance (5.6%). Conclusion The resistance rate of non-albicans candidemia isolates is increasing, particularly for C. tropicalis and C. glabrata.

BACKGROUND Scrub typhus (ST) is one of the most underdiagnosed, potentially fatal febrile diseases in the Asia-Pacific region. We conducted a comprehensive review of the risk factors of ST over 19 years using data from a nationwide database. METHODS We used data on ST from the nationwide database of the Taiwan Centers for Disease Control from 1996 to 2014 to analyse the incidence rates and relative risks of ST according to different regions. The trends of incidence rates over the study period were also evaluated. The distribution of confirmed ST cases was mapped using geographic information system software. The characteristics of confirmed ST cases and non-ST cases (cases with suspected ST but negative test findings) were compared. RESULTS Among the 38,127 reported cases, there were 6,791 (17.8%) confirmed ST cases. The overall incidence rate of ST in Taiwan was 1.49 per 100,000 residents per year. The trend of incidence rates increased over time. The Island region had the highest incidence rate (56.55 per 100,000 residents per year), followed by the Eastern region (15.13 per 100,000 residents per year). More confirmed ST cases were distributed in mountainous areas of Taiwan Main Island and Island region. Compared to non-ST cases, individuals with confirmed ST were younger (median [interquartile range] age: 44 [26-57] years versus 45 [30-60] years, p

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative viral pathogen of coronavirus disease 2019 (COVID-19), appears to have various clinical presentations and may result in severe respiratory failure. The global SARS-CoV-2-associated viral pneumonia pandemic was first reported in December 2019 in China. Based on known pharmacological mechanisms, many therapeutic drugs have been repurposed to target SARS-CoV-2. Among these drugs, remdesivir appears to be the currently most promising according to several clinical trials and reports of compassionate use. In this mini-review, we summarize the current evidence on the efficacy and challenges of remdesivir for the treatment of coronavirus disease 2019 (COVID-19).

ObjectivesThis study aimed to investigate the associations between biochemical markers, renal function, health behaviours and dementia among older people.DesignA retrospective cohort study.SettingCommunity-based health examination database from Taipei city.ParticipantsIn total, 35 434 older people were included from February 2005 to December 2012. To assess changes in renal function, we selected participants who attended health examinations at least twice and responded to the AD8 questionnaire in 2012. We excluded those with dementia at baseline.Primary outcome measuresEarly dementia was assessed using the AD8 questionnaire in 2012. Explanatory variables included demographic factors, health behaviours, biochemical markers and renal function. We used a Cox proportional hazard model to estimate the HR for early dementia onset.ResultsIndividuals with mild albuminuria (HR 1.228; 95% CI 1.066 to 1.414), lower eGFR (HR 1.549; 95% CI 1.319 to 1.820) and higher age (HR 1.022; 95% CI 1.015 to 1.028) were associated with a high risk of early dementia. Older people with no alcohol intake (HR 0.872; 95% CI 0.794 to 0.958), and higher education levels (HR 0.647; 95% CI 0.589 to 0.710) were at a low risk of early dementia.ConclusionsElevated mild albuminuria and low eGFR were associated with a high risk of early dementia in this community-based cohort. Routine health examinations for older people can help screen out the high-risk population, and clinical management might reduce or delay the risk of early dementia.

This is a rare but important case that the aspergillus should be considered when primary endophthalmitis happens especially in the immunocompromised patients even there is no other focus or receiving cataract surgery before. In most scenario, endogenous Aspergillus endophthalmitis results from disseminative aspergillosis from other organs or the patients receiving cataract surgery. Our case is unusual, because there is no other focus founded.

Takotsubo cardiomyopathy (TTC) is characterized by reversible ventricular dysfunction induced by endogenous and, occasionally, exogenous catecholamine. We present a report on a patient who developed TTC and cardiogenic shock during percutaneous coronary intervention (PCI) secondary to inadvertent norepinephrine administration. His hemodynamic status and cardiac function were totally restored within 1 week after hemodynamic support using intra-aortic balloon pump without sequela. Thus, TTC should be considered once a patient presents with symptoms mimicking acute coronary syndrome (ACS) after catecholamine administration.

Background: Intracranial hemorrhage (ICH) or infarction in dengue cases is rare but very challenging for clinicians. We report these uncommon complications of dengue patients and focused on the significant factors associated with ICH or infarction in dengue patients. Methods: This investigation was a retrospective study of 182 adult dengue patients who received brain computed tomography at three Taiwan hospitals during the 2014 and 2015 dengue outbreaks. This included 13 hemorrhage cases, 26 infarction cases and 143 cases without brain infarction or hemorrhage. Results: Among them, 13 (7.14%) suffered from ICH (6 had subdural hemorrhage, 3 had subarachnoid hemorrhage, 1 had subdural and subarachnoid hemorrhage, and 3 had intracerebral hemorrhage) and 26 (14.3%) had brain infarction. The overall mortality rate was 4/13 (30.8%) in the ICH group and 3/26 (11.5%) in the infarction group. The significant variables from the univariate analysis, including difference between 2014 and 2015, age, history of cerebrovascular accident, bone pain, arthralgia, dizziness, altered consciousness, and a higher Charlson comorbidity score. Multivariate analysis revealed that significant risk factors for ICH/infarction in dengue cases were the year of occurrence, 2014 vs. 2015 (p 4 (p = 0.01, OR = 3.764, 95% CI = 1.364–10.386) and altered consciousness (p 4, especially in the year that a higher frequency of infarction/ICH was observed.

ObjectiveThis study developed a surveillance system suitable for monitoring epidemic outbreaks and assessing public opinion in non-English-speaking countries. We evaluated whether social media reflects social uneasiness and fear during epidemic outbreaks and natural catastrophes.DesignCross-sectional study.SettingFreely available epidemic data in Taiwan.Main outcome measureWe used weekly epidemic incidence data obtained from the Taiwan Centers for Disease Control and online search query data obtained from Google Trends between 4 October 2015 and 2 April 2016. To validate whether non-English query keywords were useful surveillance tools, we estimated the correlation between online query data and epidemic incidence in Taiwan.ResultsWith our approach, we noted that keywords 感冒 (‘common cold’), 發燒 (‘fever’) and 咳嗽 (‘cough’) exhibited good to excellent correlation between Google Trends query data and influenza incidence (r=0.898, pConclusionsThese results suggested that Google Trends can be a good surveillance tool for epidemic outbreaks, even in Taiwan, the non-English-speaking country. Online search activity indicates that people are concerned about epidemic diseases, even if they do not visit hospitals. This prompted us to develop useful tools to monitor social media during an epidemic because such media usage reflects infectious disease trends more quickly than does traditional reporting.

Both dengue virus (DENV) and hepatitis C virus (HCV) belong to the Flaviviridae family and could induce hepatitis. We aimed to investigate the interference between them. In total, 515 patients confirmed with dengue fever (DF) were enrolled. Thirty-two patients (6.21%) were seropositive for anti-HCV; 12 of 32 anti-HCV-positive patients had detectable HCV-RNA at presentation of DF. The proportion of dengue hemorrhagic fever was comparable between patients with or without anti-HCV and between those with or without HCV-RNA. Eleven of 32 patients received HCV-RNA testing during a median interval of 23 months after DF, which revealed significantly increased HCV-RNA levels (5.43 ± 0.77 vs 3.09 ± 1.24 log IU/mL, follow-up vs acute-DF phase; P = .003). Four of 11 patients with baseline HCV-RNA values before DF demonstrated a nadir viremia during acute DF. We also included age-, sex-, and follow-up duration–matched HCV-monoinfected patients as controls; higher delta HCV-RNA changes were demonstrated in patients with DF than in controls during the follow-up period (2.34 ± 1.15 vs –0.27 ± 0.76 log IU/mL; P

No abstract available Keywords: Big data integration and analytics; COVID-19; Prevention strategies.

Objectives: This study was performed to examine the current status of Zika and the effects of pre-existing dengue immunity on Zika virus (ZIKV) infection in Southern Taiwan. Methods: A phylogenetic tree was used to analyze the phylogeny of detected ZIKVs. Paired sera from dengue patients were collected for the determination of dengue and Zika infection. Plaque reduction neutralization tests (PRNT) and quantitative reverse transcription PCR (qRT-PCR) were used to determine the titers of neutralizing antibodies and viruses, respectively. An antibody-dependent enhancement (ADE) assay was used to evaluate the effect of anti-dengue antibodies on ZIKV infection. Results: Epidemiological data indicated the continuous importation of ZIKV infection from neighboring Zika epidemic countries into Taiwan. A total of 78 dengue patients were enrolled and 21 paired serum samples were obtained. PRNT90 results for the 21 samples identified eight cases of primary dengue infection and 13 cases of secondary dengue infection; two samples were positive for ZIKV (MR766). Results from the ADE assay indicated that convalescent sera from primary and secondary dengue infection patients displayed significant ADE of the ZIKV infection when compared to healthy controls (p < 0.05). Conclusions: This study suggests that pre-existing dengue immunity facilitates ZIKV infection and that the continuous importation of ZIKV infection may pose a threat to indigenous Zika emergence in Southern Taiwan. Keywords: Zika, Dengue, Importation, Taiwan, Antibody-dependent enhancement, Plaque reduction neutralization test

Background No study has reported the epidemiology of AIDS-related opportunistic illnesses (AOIs) in patients with newly diagnosed HIV infection in Taiwan in the past decade. Understanding the current trends in AOI-related morbidity/mortality is essential in improving patient care and optimizing current public health strategies to further reduce AOIs in Taiwan in the era of contemporary highly active antiretroviral therapy (HAART). Methods Eligible patients were evaluated at two referral centers between 2010 and 2015. The patients were stratified by date of diagnosis into three periods: 2010–2011, 2012–2013, and 2014–2015. The demographics, HIV stage at presentation according to the United States CDC 2014 case definition, laboratory variables, and the occurrence of AOIs and associated outcomes were compared among the patients. Logistic regression and Cox regression were respectively used to identify variables associated with the occurrence of AOIs within 90 days of HIV enrollment and all-cause mortality. Results Over a mean observation period of 469 days, 1264 patients with newly diagnosed HIV with a mean age of 29 years and mean CD4 count of 275 cells/μL experienced 394 AOI episodes in 290 events. At presentation, 37.7% of the patients had AIDS; the frequency did not significantly differ across groups. The overall proportion of AOIs within the study period was 21.0%, and no decline across groups was observed. The majority of AOIs (91.7%) developed within 90 days of enrollment. All-cause and AOI-related mortality did not significantly differ across groups. Throughout the three study periods, AOIs remained the main cause of death (47/56, 83.9%), especially within 180 days of enrollment (40/42, 95.2%). A CD4 cell count of

Background/purpose: For high risk of central line-associated bloodstream infections (CLABSIs) in patients of intensive care units (ICUs) and scarcely epidemiology and therapeutic recommendations in Asia, we aimed to evaluate the annual change in epidemiology, antibiogram, and risk factors for 14-day mortality. Methods: A retrospective study of ICUs patients with CLABSIs at a medical center in Taiwan (2010–2016), where central line care bundle implemented since 2014, by reviewing clinical data, pathogens, and the antibiogram. Results: Gram-negative bacteria (59.3%) were main microorganisms of CLABSIs, and 9.0% of all GNB were MDROs. Acinetobacter spp., Enterobacter spp., and Stenotrophomonas maltophilia were the most frequently isolated. In multivariate analysis, malignancy, inadequate empirical antimicrobial therapy, inadequate definite antimicrobial therapy, and infection by fungi or multidrug-resistant organisms (MDROs) were associated with 14-day mortality (all p

The spread of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has become a major public health threat worldwide. Area covered: A thorough systematic literature review describing the current evidence and future prospects of therapeutic options for infections caused by ESBL-producing Enterobacteriaceae. Expert commentary: The methods of detecting ESBLs have been evolving. The Clinical and Laboratory Standards Institute and the European Committee on Antimicrobial Susceptibility Testing lowered the MIC breakpoints of cephalosporins against ESBL-producing Enterobacteriaceae in 2010. Phenotypic testing for ESBLs is no longer recommended. Instead, the selection of appropriate antimicrobial agents largely depends on the report of minimum inhibitory concentrations (MICs). To date, therapeutic options for these multidrug-resistant organisms remain limited. The clinical efficacy of piperacillin/tazobactam and cefepime on in vitro-susceptible ESBL-producing Enterobacteriaceae remains a concern. Many studies found an in vitro-in vivo discordance based on current breakpoints. Carbapenems are the most reliable antibiotics for severe infections caused by ESBL-producing Enterobacteriaceae. However, their overuse has led to a serious problem of increasing drug resistance. Recently, ceftolozane/tazobactam and ceftazidime/avibactam have been approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections. The introduction of these new β-lactam/β-lactamase inhibitor combinations offers new carbapenem-sparing options for the treatment of ESBL infections.

OBJECTIVE This was a prospective study aiming to investigate whether levofloxacin plus bismuth-based quadruple therapy was more effective than levofloxacin-based triple therapy after failed first-line eradication therapies for Helicobacter pylori (H. pylori) infection. METHODS Sixty-seven patients infected with H. pylori were randomly assigned to two groups; the levofloxacin plus bismuth-based quadruple therapy group (RBAL [n = 33]; rabeprazole 20 mg twice daily, bismuth subcitrate 120 mg four times daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days) and the levofloxacin-based triple therapy group (RAL [n = 34]; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days). Endoscopy was performed 4–8 weeks after H. pylori eradication to assess treatment response. We followed up patient response and compliance and checked their resistance to antibiotics. RESULTS Intention-to-treat analysis revealed that both groups had similar eradication rates (RBAL vs RAL: 84.8% [95% confidence interval {CI} 72.6–97.1%] vs 67.6% [95% CI 51.9–83.4%], P = 0.0987). No significant differences in compliance or adverse events were found (P = 0.9829 and 0.0720). Epsilometer test showed that most eradication failure cases were levofloxacin-resistant. CONCLUSIONS Adding bismuth subcitrate to levofloxacin-based triple therapy was not more effective than not doing so, but no further side effects were noted. Both eradication therapies were equally safe and patients had the same tolerance to both regimens. Resistance rate to levofloxacin may be important when choosing second-line therapy.

Background Evaluation and feedback is a core hand hygiene (HH) improvement strategy. The covert observation method avoids observation bias inherent to the overt method. The aim of the study was to observe HH compliance by a novel covert method in a real-world setting. Methods We conducted a 2-year, nationwide, prospective, observational study in teaching hospitals across Taiwan. Medical students and students who may have contact with patients in their careers were recruited as participants. A novel, shorthand notation method for covert observation was used. Observation results were reported through a study website. Results There were a total of 25,379 HH opportunities covertly observed by 93 observers. Overall HH compliance was 32.0%. Health care workers had the highest HH compliance for indication 4 (42.6%), and the lowest for indication 5 (21.7%). Overall handrubbing percentage was high, reaching 83.6%. The HH compliance increased significantly with an increase in the number of indications within 1 HH opportunity ( P Conclusions The overall HH compliance by the covert observation method was low. An innovative shorthand notation method facilitated covert observation, and website reporting was demonstrated to be feasible for large-scale observation.

Background The decline of the incidence rate of tuberculosis in Taiwan has been partly attributed to the launch of the directly observed therapy short course (DOTS) program in 2006, followed by the DOTS-Plus in 2007. However, with the phasing out of the specialized tuberculosis care system and the declining incidence, clinical workers in Taiwan might become less familiar with the presentation of tuberculosis. Complementing the patient-pathway analysis with health system delay estimates, the objective of this study is twofold: to estimate the alignment between patient care initiation and the availability of prompt diagnostic and treatment services, and to identify the risk factors of delayed tuberculosis treatment. Methods The study population included all Taiwanese patients with incident tuberculosis in 2013. We (1) identified 11,507 incident tuberculosis patients from the 2013 National TB Registry, and (2) linked 10,932 Taiwanese from the registry to the 2012–2013 National Health Insurance Research Database. We assessed patient’s care-seeking pathways and associated the determinants of health system delay in a Cox model. Results The overall health system delay was 46 days. We found that 20.5 and 3.5% of 10,932 tuberculosis patients were diagnosed and treated respectively at the initial visit to seek care for TB-related symptoms. Risk factors related to the prolonged health system delay included female gender (adjusted HR = 0.921, 95% CI: 0.884, 0.960), age > =65 years (adjusted HR = 0.720, 95% CI: 0.692, 0.750), non-severe (chest X-ray without cavities) (adjusted HR =0.721, 95% CI 0.683–0.760), chronic respiratory diseases (adjusted HR = 0.544, 95% CI: 0.522, 0.566), living in long-term care facilities (adjusted HR = 0.580, 95% CI: 0.525,0.640), an initial visit at a primary care clinic (adjusted HR = 0.588, 95% CI: 0.565, 0.612), and living in southern Taiwan (adjusted HR = 0.887, 95% CI: 0.798, 0.987). Conclusions The low access to TB diagnostic and treatment services at the initial visit and the prolonged health system delay indicate inefficiency in the health care system. Strengthening training of physicians at public hospitals and health workers at nursing homes might improve the efficiency and timeliness of tuberculosis diagnosis and treatment in Taiwan.

Objectives: This study examined the epidemiological, clinical, and immunological characteristics of the 2015 dengue outbreak in Taiwan. Methods: Clinical data were collected from dengue fever (DF) and dengue hemorrhagic fever (DHF) patients. A phylogenetic tree was used to analyze the source of the outbreak strain. Paired plasma samples from DF/DHF patients were used for antibody-dependent enhancement (ADE) assay and cytokine multiplex biometric immunoassay to validate the immunological mechanism. Results: This outbreak mainly occurred in two of the southern cities of Taiwan: Tainan (n = 22 777; 52%) and Kaohsiung (n = 19 784; 45%). A high DHF death rate was noted (34.6%). The case (DHF) and control (DF) study indicated that older age (>60 years), type II diabetes, and hypertension were risk factors correlated with the development of DHF (p

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 (n = 154), per-protocol (n = 147), and safety (n = 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.

BACKGROUND: Leptospirosis (LS) is a neglected tropical zoonosis of global importance. A nationwide investigation of characteristics, epidemiology, risk factors and outbreak is crucial for awareness of this disease. METHODS: A nationwide database of reported LS cases from October 2007 to December 2014 obtained from the Centers for Disease Control, Taiwan, was analysed. Geographic information system software was used to map the distribution of confirmed LS cases and pigs. Cross‐matching with the databases of Q fever, scrub typhus and murine typhus was conducted to identify possible coinfections. RESULTS: A total of 10,917 reported cases of LS were recorded in the database, which included 665 (6.1%) confirmed LS and 10,252 (93.9%) non‐confirmed LS cases. The major residences of confirmed LS were the Kaohsiung‐Pingtung (248, 37.3%) and Taipei (174, 26.2%) regions. The average annual incidence was 0.4/100,000 people. Compared with non‐confirmed LS cases, confirmed LS cases had significantly higher percentages of male gender (83.6% vs. 67.9%, p

Multicentre surveillance of antimicrobial susceptibility of clinically important Gram-negative bacteria (GNB) from 16 Taiwanese hospitals was performed. Escherichia coli (n = 398), Klebsiella pneumoniae (n = 346), Pseudomonas aeruginosa (n = 252) and Acinetobacter baumannii complex (ABC) (n = 188) bloodstream isolates, non-typhoidal Salmonella (n = 230) and Shigella flexneri (n = 18) from various sources were collected. Antimicrobial MICs were determined using broth microdilution. Genes encoding K. pneumoniae carbapenemases (KPCs), New Delhi metallo-β-lactamases (NDMs), Verona integron-encoded metallo-β-lactamase (VIM), OXA-48-like carbapenemase (OXA-48) as well as mcr-1–5 genes were detected by molecular methods. Rates of carbapenem non-susceptibility were 2.8%, 9.0%, 0.4%, 0%, 10.3% and 48.8% for E. coli, K. pneumoniae, Salmonella, Shigella, P. aeruginosa and ABC, respectively. For carbapenemases, one (0.3%) E. coli harboured blaNDM-1. Fifteen (4.3%), two (0.6%) and two (0.6%) K. pneumoniae contained blaKPC, blaOXA-48 and blaVIM, respectively. Two (0.5%) E. coli and fourteen (4.0%) K. pneumoniae were non-wild-type according to the colistin MIC. Among Enterobacteriaceae with a colistin MIC ≥ 2 mg/L, mcr-1 was detected in one E. coli, two K. pneumoniae and three Salmonella spp. All three mcr-1-positive Salmonella isolates were collected from community-acquired infections; none of the six mcr-1-positive Enterobacteriaceae were carbapenem-resistant. Carbapenem resistance has increased among clinically important GNB, especially among hospital-acquired infections. blaKPC, especially the blaKPC-2 variant, was detected in approximately one-half of the carbapenem-resistant K. pneumoniae isolates in this study. Although resistance rates to colistin remained low among Enterobacteriaceae, the finding of mcr-1 from different species raises concern of potential dissemination.

Carbapenems are considered as last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. With the increasing use of carbapenems in clinical practice, the emergence of carbapenem-resistant pathogens now poses a great threat to human health. Currently, antibiotic options for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) are very limited, with polymyxins, tigecycline, fosfomycin, and aminoglycosides as the mainstays of therapy. The need for new and effective anti-CRE therapies is urgent. Here, we describe the current understanding of issues related to CRE and review combination therapeutic strategies for CRE infections, including high-dose tigecycline, high-dose prolonged-infusion of carbapenem, and double carbapenem therapy. We also review the newly available antibiotics which have potential in the future treatment of CRE infections: ceftazidime/avibactam, which is active against KPC and OXA-48 producers; meropenem/vaborbactam, which is active against KPC producers; plazomicin, which is a next-generation aminoglycoside with in vitro activity against CRE; and eravacycline, which is a tetracycline class antibacterial with in vitro activity against CRE. Although direct evidence for CRE treatment is still lacking and the development of resistance is a concern, these new antibiotics provide additional therapeutic options for CRE infections. Finally, we review other potential anti-CRE antibiotics in development: imipenem/relebactam and cefiderocol. Currently, high-dose and combination strategies that may include the new β-lactam/β-lactamase inhibitors should be considered in severe CRE infections to maximize treatment success. In the future, when more treatment options are available, therapy for CRE infections should be individualized and based on molecular phenotypes of resistance, susceptibility profiles, disease severity, and patient characteristics. More high-quality studies are needed to guide effective treatment for infections caused by CRE.

A main pathological feature of severe dengue virus infection is endothelial hyperpermeability. We demonstrate that elevated serum hyaluronan levels (≥70 ng/ml)during early infection is an independent predictor for occurrence of warning signs, and thus severe dengue fever. High circulating levels of the viral protein NS1, indicative of disease severity, correlate with high concentration of serum hyaluronan. NS1 exposure decreased the expression of CD44 in differentiating endothelial cells impairing the integrity of vessel-like structures, and promoted the synthesis of hyaluronan in dermal fibroblasts and endothelial cells in synergy with dengue-induced pro-inflammatory mediators. Deposited hyaluronan-rich matrices around cells recruited CD44-expressing macrophages, thus perpetuating inflammation. Perturbed hyaluronan-CD44 interactions enhanced endothelial permeability through modulation of VEcadherin and cytoskeleton re-organization, and exacerbated the NS1 induced disruption of endothelial integrity. Thus, pharmacological targeting of hyaluronan biosynthesis and/or its CD44-mediated signaling may limit the life-threatening vascular leakiness during severe dengue virus infection. Funding Statement: This work was supported in part by grants from the Swedish Cancer Society (2015- 0778), the Swedish research Council (2015-02757), the Ludwig Institute for Cancer Research, Uppsala University, the Ministry of Science and Technology, Taiwan (106- 2314-B-037-088- and 106-2915-I-037-501-), Kaohsiung Medical University Hospital (KMUH103-3T05) and Academy of Finland. Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: The human study protocol was approved by the Institutional Review Board (IRB) of Kaohsiung Medical University Hospital (IRB Number: KMUH-IRB-20110451). Informed consent was obtained from all subjects.

African swine fever (ASF) is a highly contagious hemorrhagic viral disease associated with high fatality rates in domestic and wild pigs. It is caused by the African swine fever virus (ASFV) [1]. A...

BackgroundInfection is the most common predisposing factor for diabetic ketoacidosis (DKA); however, studies are rare that have investigated the clinical outcomes of septic patients with infection-precipitated DKA.MethodsA retrospective cohort study was conducted at a tertiary hospital from 2004 to 2013. Patients with DKA in whom the presence of a predisposing infection was confirmed were enrolled. Characteristics at initial presentation, primary infection sources, and causative microorganisms were compared between the nonacute kidney injury (non-AKI) group and acute kidney injury (AKI) group at each stage. Risk factors for the development of failure-stage AKI and its outcomes were also analyzed.ResultsOne hundred and sixty DKA episodes were assessed. The most common infection sites were the urinary and respiratory tracts. The leading causative microorganism was Escherichia coli, followed by Klebsiella pneumoniae. A complicated/severe infection state [odds ratio (OR), 15.27; p

ObjectivesIt is not known if the incidences of autoimmune diseases are higher in individuals living with HIV infection or AIDS. Our study investigated the incidences of autoimmune diseases among people living with HIV/AIDS (PLWHA) in Taiwan during 2000–2012.MethodsThe Taiwan National Health Insurance Research Database was used to identify PLWHA. The incidence densities of systemic and organ-specific autoimmune diseases were calculated, and age-adjusted, sex-adjusted and period-adjusted standardised incidence rates (SIRs) were obtained by using two million people from the general population as controls. To examine the effects of highly active antiretroviral therapy (HAART) on the incidence of autoimmune diseases, the incidence densities and SIRs of autoimmune diseases were calculated after stratifying PLWHA by HAART status.ResultsOf the 20 444 PLWHA identified, the overall mean (SD) age was 30.1 (11.0) years; 67.2% of the subjects received HAART. As compared with the general population, SIRs were higher for incident Sjögren syndrome (SIR=1.64; 95% CI 1.24 to 2.13), psoriasis (SIR=2.05; 95% CI 1.67 to 2.48), systemic lupus erythematosus (SLE) (SIR=2.59; 95% CI 1.53 to 4.09), autoimmune haemolytic anaemia (SIR=35.06; 95% CI 23.1 to 51.02) and uveitis (SIR=2.50; 95% CI 2.05 to 3.02), but were lower for incident ankylosing spondyloarthritis (SIR=0.70; 95% CI 0.48 to 0.99). When the effect of HAART on incident autoimmune diseases was considered, PLWHA who received HAART had higher SIRs for psoriasis, autoimmune haemolytic anaemia and uveitis, but had lower risks of rheumatoid arthritis (RA) and ankylosing spondyloarthritis. In contrast, PLWHA who did not receive HAART had higher SIRs for Sjögren syndrome, psoriasis, RA, SLE, scleroderma, polymyositis, autoimmune haemolytic anaemia and Hashimoto's thyroiditis.ConclusionsPLWHA had higher risks of incident Sjögren syndrome, psoriasis, SLE, autoimmune haemolytic anaemia and uveitis.

The continuing increase in multidrug-resistant organisms (MDROs) worldwide has created new challenges in treating complicated intra-abdominal infections (cIAIs). A number of novel antimicrobial agents have been developed against resistant pathogens. To target extended-spectrum β-lactamase (ESBL)-producing pathogens, novel β-lactam antibiotics, such as ceftolozane/tazobactam, ceftazidime/avibactam, aztreonam/avibactam, imipenem/relebactam and S-649266, are antimicrobial alternatives for cIAIs. Two new drugs, eravacycline and plazomicin, have activity against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, carbapenem-resistant Acinetobacter baumannii and ESBL-producers. New lipoglycopeptides and oxazolidinones provide feasible options against resistant Gram-positive pathogens. These novel antimicrobials may play a role in improving the clinical outcomes of cIAIs caused by MDROs.

The effects of various antimicrobial stewardship programs (ASPs) on both antibiotic consumption and resistance among different hospitals within the same insurance system have rarely been investigated.This 6-year retrospective study included three medical centers with similar facilities and infection control measures in Taiwan. These hospitals used different types of ASPs: one had a hospital-wide preauthorization requirement by infectious diseases physicians for all broad-spectrum antibiotics, covering all intensive care units; the second used the same program, but excluded all intensive care units; and the third used postprescription review only. The nonsusceptibility of unduplicated isolates of gram-negative bacilli causing health care-associated infections and consumption of broad-spectrum antibiotics were analyzed.Overall, the usage of broad-spectrum antibiotics of all classes escalated significantly over time in all three hospitals, but consumption was lowest under the hospital-wide preauthorization program. Under this ASP, despite a 2-fold increase in the total broad-spectrum antibiotic consumption during study period, some declining trends of resistance were found, including ciprofloxacin-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, and carbapenem-resistant P. aeruginosa. By contrast, the other two hospitals with preauthorization program excluding all intensive care units and postprescription review had similar high broad-spectrum antibiotic consumption, comparable growing trends of resistant strains in general, and the correlations of antibiotic consumption and resistance were basically positive. Carbapenem-resistant A. baumannii increased significantly over time in all three hospitals.This interhospital comparison suggested that hospital-wide preauthorization program is the most effective to reduce key gram-negative bacilli resistance, with the exception of carbapenem-resistant A. baumannii.