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Introduction: COVID-19 poses risks and leads to complications for vulnerable populations, including children. Unreported cases of COVID-19 among children hinder our understanding of the true disease burden. In this study, we aimed to investigate the proportion of children who report no prior infection to SARS-CoV-2 but who nevertheless exhibit serological evidence of prior infection. Methods: Between November 2022 and February 2023, we recruited children and adolescents under 19 years of age who lacked a prior history of SARS-CoV-2 infection. Participants underwent SARS-CoV-2 antibody testing to assess the presence of IgG antibodies specific to nucleocapsid (N) and spike (S) proteins. Demographic and contact information were also collected. Results: Among 260 COVID-19-free children, the overall anti-N antibody positivity rate, which varied across age groups (4%–25%), was 9.2% (24/260). Contact with individuals who were positive for COVID-19, particularly the children's mothers, significantly increased the likelihood of antibody positivity. The median age of the 34 children who remained unvaccinated against COVID-19 was lower than that of the children who were vaccinated (6.5 vs. 9 years; p

Background: The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales. Methods: This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and β-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018–2019) and during the COVID-19 pandemic (2020–2021). Results: A total of 1231 Enterobacterales isolates were collected, predominantly Escherichia coli (55.6%) and Klebsiella pneumoniae (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, p

Objectives: WHO has recommended same-day antiretroviral therapy (SDART) initiation since 2017; however, higher attrition rates were noted in developing countries. Methods: We included newly diagnosed people with HIV (PWH) from 2018 to 2022 at 18 hospitals around Taiwan. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid initiation as starting ART within 14 days of diagnosis. A composite unfavorable outcome was defined as death after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failure or rebound at 12 months. Results: At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with plasma HIV-1 RNA 30 years were less likely to have LTFU (aHR 0.44, 95% CI 0.28-0.70). PWH aged >30 years (aHR 0.59, 95% CI 0.41-0.85) and gay, bisexual, and men who have sex with men (GBMSM) (aHR 0.50, 95% CI 0.32-0.79) were less likely to have composite unfavorable outcomes. Conclusions: SDART and rapid ART initiation resulted in comparable clinical outcomes and viral suppression rates. PWH aged >30 years and GBMSM were less likely to have unfavorable outcomes.

Background: The efficacy of inhaled corticosteroid (ICS) in the treatment of patients with COVID-19 has been evaluated in randomized controlled trials (RCTs), however, their findings are not consistent. Methods: PubMed, Embase, Cochrane Library, ClinicalTrials.gov, Scopus, Web of Science and Google Scholar were searched to June 10, 2023. Only RCTs that investigated the clinical efficacy and safety of ICS for patients with COVID-19 were included. Results: Eleven RCTs were included. ICS users had significantly higher rate of symptom alleviation at day 14 than the control group (risk ratio [RR], 1.13; 95% CI, 1.04–1.23; I2 = 42%). Additionally, no significant difference between the ICS users and the control group was observed in the composite outcome of urgent care, emergency department (ED) visit or hospitalization (RR, 0.43; 95% CI, 0.08–2.48; I2 = 85%) and hospitalization or death (RR, 0.85; 95% CI, 0.64–1.12; I2 = 0%). Finally, ICS user had a non-significantly lower risk of death at day 28 than the control group (0.63% vs 0.99%; RR, 0.82; 95% CI, 0.43–1.56; I2 = 0%). Conclusions: Additional ICS use, particularly inhaled budesonide may help symptom relief in patients with COVID-19. However, ICS use did not help reduce the risk of urgent care, ED visit, hospitalization, or death.

Background: Enterobacterales carrying blaNDM represent an emerging challenge in treating infectious diseases. In this study, we aimed to investigate the characteristics of blaNDM-producing Enterobacterales from three hospitals in southern Taiwan. Methods: Enterobacterales strains that were nonsusceptible to more than one carbapenem (ertapenem, meropenem, imipenem, or doripenem) were collected from hospitalized patients. Molecular typing for New Delhi metallo-β-lactamase (NDM) and antibiotic susceptibility tests were performed, followed by multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and plasmid analysis by PCR-based replicon typing. Results: A total of 1311 carbapenem-nonsusceptible Enterobacterales were isolated from 2017 to 2021. blaNDM-encoding genes were detected in 108 isolates, with 53 (49.1%) harboring blaNDM-1 and 55 (50.9%) harboring blaNDM-5. The rate of blaNDM-1 detection among isolates decreased to 2% in 2021. However, the rate of E. coli harboring blaNDM-5 increased from 1% to 12% of total isolates during the study period. Of 47 NDM-5-positive E. coli isolates, 44 (93.6%) were ST8346 with high genetic relatedness. E. coli ST8346 isolates showed high-level resistance to both carbapenems and aminoglycosides. Most (38 out of 47, 80.9%) blaNDM-5-harboring E. coli isolates co-harbored blaOXA-181. We analyzed the regions harboring blaNDM-5 in E. coli ST8346 via PCR amplification. blaNDM-5 and blaOXA-181 were located on two separate plasmids, IncF and IncX3, respectively. Conclusion: The dissemination of E. coli ST8346 caused an increase in blaNDM-5 and blaOXA-181 co-harboring Enterobacterales in southern Taiwan, which show high-level resistance to both carbapenems and aminoglycosides. We identified a distinct IncF plasmid encoding blaNDM-5 that has the potential for rapid spread and needs further surveillance.

Background: In Taiwan, the prevalence of COVID-19 was low before April 2022. The low SARS-CoV-2 seroprevalence in the population of Taiwan provides an opportunity for comparison with fewer confounding factors than other populations globally. Cycle threshold (Ct) value is an easily accessible method for modeling SARS-CoV-2 dynamics. In this study, we used clinical samples collected from hospitalized patients to explore the Ct value dynamics of the Omicron variant infection. Methods: From Jan 2022 to May 2022, we retrospectively included hospitalized patients tested positive by nasopharyngeal SARS-CoV-2 PCR. We categorized the test-positive subjects into different groups according to age, vaccination status, and use of antiviral agents. To investigate the nonlinear relationship between symptom onset days and Ct value, a fractional polynomial model was applied to draw a regression line. Results: We collected 1718 SARS-CoV-2 viral samples from 812 individuals. The Ct values of unvaccinated individuals were lower than those of vaccinated persons from Day 4 to Day 10 after symptom onset. The Ct value increased more rapidly in those individuals with antiviral drug treatment from Day 2 to Day 7. In elderly individuals, the Ct values increased slowly from Day 5 to Day 10, and the increasing trend was unique compared with that in children and adults. Conclusion: Our study demonstrated the primary viral infection dynamics of the Omicron variant in hospitalized patients. Vaccination significantly affected viral dynamics, and antiviral agents modified viral dynamics irrespective of vaccination status. In elderly individuals, viral clearance is slower than that in adults and children.

Background: Streptococcus gallolyticus subsp. pasteurianus (SGSP) is a commensal in the intestinal tract and a potential pathogen of neonatal sepsis. During an 11-month period, four consecutive cases of SGSP sepsis were identified in one postnatal care unit (unit A) without evidence of vertical transmission. Therefore, we initiated this study to investigate the reservoir and mode of transmission of SGSP. Method: We performed cultures of stool samples from healthcare workers in unit A and unit B (another unit without SGSP sepsis). If SGSP was positive in feces, we performed isolate pulsotyping and genotyping by using pulsed-field gel electrophoresis (PFGE) and analyzing random amplified polymorphic DNA (RAPD) patterns, respectively. Results: Five staff members in unit A showed positivity for SGSP. All samples from unit B were negative. We identified two major pulsogroups (groups C and D) by PFGE. In group D, the strains isolated from 3 consecutive sepsis patients (P1, P2 and P3) were closely related and clustered together as those from 2 staff members (C1/C2, C6). One staff (staff 4) had a direct contact history with patient (P1) confirmed to have the same clone. The last isolate of the patient in our study (P4) belonged to a distinct clone. Conclusion: We found prolonged gut colonization of SGSP in healthcare workers and its epidemiological relatedness to neonatal sepsis. Fecal-oral or contact transmission is a possible route of SGSP infection. Fecal shedding among staff may be associated with neonatal sepsis in healthcare facilities.

ABSTRACT: Objective: Both ertapenem and other carbapenems, including imipenem, meropenem, and doripenem, are recommended in the treatment of extended-spectrum-β-lactamase (ESBL)-producing Enterobacterales infection. However, whether ertapenem is as effective as other carbapenems for ESBL-producing Enterobacterales remains unclear. Therefore, this meta-analysis was conducted to compare the clinical efficacy of ertapenem versus other carbapenems in the treatment of ESBL-producing Enterobacterales infection. Methods: PubMed, Web of Science, and Cochrane Library were searched from their inception to 29 November 2022. Only studies comparing ertapenem and other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections were included. Results: A total of six studies meeting selection criteria were identified. Overall, ertapenem was associated with a significantly lower 30-d mortality when compared with other carbapenems (10.7% [46/431] vs. 17.7% [104/586]; risk ratio [RR], 0.61; 95% CI: 0.40–0.91). The ertapenem group exhibited a significantly shorter length of hospital stay than the other carbapenem groups (mean differences, -6.02 d; 95% CI, -9.39 to -2.64). No significant differences were noted between ertapenem and other carbapenem groups in terms of rates of clinical cure or improvement (RR, 1.11; 95% CI: 0.97–1.25) and microbiological eradication (RR, 1.01; 95% CI: 0.97–1.06). Conclusions: Ertapenem could be as effective as other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections.

Background: The association between N-acetylcysteine (NAC) and COVID-19 remains undetermined; therefore, this meta-analysis assessed the clinical efficacy of NAC in the treatment of patients with COVID-19. Methods: This study searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for studies published from their inception to December 17, 2022. Only randomized controlled trials (RCTs) that assessed the clinical efficacy of NAC for patients with COVID-19 were included. Results: Five RCTs involving 651 patients were included. There was no significant difference in mortality between the study group receiving NAC and the control group (15.6 % [50/320] vs. 32.3 %, [107/331]; risk ratio [RR]: 0.58; 95 % confidence interval [CI]: 0.24–1.40). In addition, the two groups did not differ with respect to the incidence of invasive mechanical ventilation (RR: 0.93; 95 % CI: 0.65–1.33), the risk of intensive care unit (ICU) admission (RR: 0.86; 95 % CI: 0.62–1.21), the length of hospital stay (mean difference [MD]: 0.17 days; 95 % CI: −0.67–1.01), and the length of ICU stay (MD: −0.77 days; 95 % CI: −2.97–1.42). Conclusions: The administration of NAC did not improve the clinical outcomes of patients with COVID-19; its routine use is not recommended for patients with SARS-CoV-2 infections.

ABSTRACTThe emerging pathogen Elizabethkingia anophelis poses severe threats to public health and has caused several outbreaks. The efficacy of antimicrobials is limited due to the pathogen’s innate multi-drug resistance to most antibiotics. Hence, novel approaches to treat E. anophelis infections are urgently needed. This study evaluated the immunogenic and protective effects of the imipenem-induced outer membrane vesicles (iOMVs) of E. anophelis as a vaccine. Mice immunized with iOMVs were completely protected during lethal-dose challenges. Passive immunization with hyperimmune sera and splenocytes conferred protection against lethal pneumonia. iOMVs also induced Th1-, Th2-, and Th17-driven immune responses. Immunization with iOMVs increased IgG1 and IgG2c isotype levels, and the antisera from immunized mice promoted complement-dependent bactericidal and opsonophagocytic activities against E. anophelis C08. Our study suggests that E. anophelis iOMVs are a promising vaccine candidate for preventing and treating E. anophelis infections and provides insights into the use of OMVs in vaccine development against the clinically emergent E. anophelis.IMPORTANCEElizabethkingia anophelis, a Gram-negative pathogen, causes infections such as bacteraemia, pneumonia, and neonatal meningitis. The pathogen resists most antimicrobial classes, making novel approaches urgently needed. In natural settings, Gram-negative bacteria secrete outer membrane vesicles (OMVs) that carry important molecules in the bacterial life cycle. These OMVs are enriched with proteins involved in virulence, survival, and carbohydrate metabolism, making them a promising source for vaccine development against the pathogen. This study investigated the efficacy of imipenem-induced OMVs (iOMVs) as a vaccine candidate against E. anophelis infection in a mouse pneumonia model. Mice immunized with iOMVs were completely protected during lethal-dose challenges. Passive immunization with hyperimmune sera and splenocytes conferred protection against lethal pneumonia. Further investigation is needed to understand the mechanisms underlying the protective effects of iOMV-induced passive immunity, such as the action on specific antibody subclasses or T cell subsets.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

Objectives: Real-world experience with coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is sparse as a switch regimen among people living with HIV (PLWH) having achieved viral suppression after previous virologic failures with the emergence of K65N/R. Methods: In this retrospective study, PLWH aged ≥20 years who had previous virologic failures with emergent K65N/R were included for switching to BIC/FTC/TAF after having achieved plasma HIV RNA load (PVL) 50 copies/ml) at week 48 using a modified US Food and Drug Administration snapshot algorithm. Results: A total of 72 PLWH with K65N/R who switched to BIC/FTC/TAF were identified. A total of 42 (59.7%) had concurrent M184V/I, and 9 (12.5%) had ≥1 thymidine analog mutations. The median duration of viral suppression was 4.7 years (interquartile range 2.3-5.8), and 97.2% (n = 70) had PVL

Abstract Introduction International treatment guidelines recommend the rapid initiation of antiretroviral therapy (ART) with bictegravir (B)/emtricitabine (F)/tenofovir alafenamide (TAF) and dolutegravir (DTG)-based regimens for treatment-naïve persons living with HIV (PLWH) irrespective of their disease stage. However, we lack evidence of the virological efficacy, virological failure, and tolerability of coformulated B/F/TAF and DTG/ABC/3TC regimens in persons living with advanced HIV (PLWAH; defined as persons with a CD4+ count of

Purpose: In this study, we aimed to assess the geographic distribution and molecular characteristics of β-lactamases among Enterobacterales isolates causing intra-abdominal infections (IAIs) from 2015 to 2018 in the Asia–Pacific region. Method: Isolates were investigated for extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases using multiplex PCR assays and full-gene DNA sequencing. Result: A total of 832 Enterobacterales isolates from 8 different countries with β-lactamase genes were analysed. Plasmid-mediated ESBLs and AmpC β-lactamases were encoded in 598 (71.9 %) and 314 (37.7 %) isolates, respectively. In 710 (85.3 %) carbapenemase-negative isolates, positivity for both AmpC β-lactamases and ESBLs was identified in 51 (8.5 %) Escherichia coli and 24 (3.4 %) Klebsiella pneumoniae isolates. The most prevalent countries were Taiwan and Vietnam, and the co-occurrence of CMY/CTX-M in E. coli and DHA-1/ESBLs in K. pneumoniae was predominant. All isolates showed high susceptibility to colistin, but susceptibility to carbapenems varied among different resistance mechanism combinations. Among 122 (14.7 %) isolates encoding carbapenemase, NDM (n = 67, including 64.2 % NDM-1) was the most common, followed by the OXA-48-type (n = 49), KPC (n = 24) and IMP (n = 4). The most prevalent country was Thailand (n = 44), followed by Vietnam (n = 35) and the Philippines (n = 21). Twenty-two isolates were found to encode multiple carbapenemases, 16 of which were collected from Thailand and harbored NDM-1, OXA-232 and CTX-M-15. Despite high susceptibility to amikacin, susceptibility to colistin was only 56 %. Conclusion: The emergence of carbapenem-non-susceptible AmpC/ESBL co-occurring Enterobacterales and colistin non-susceptible carbapenemases co-occurring K. pneumoniae highlights potential therapeutic challenges in the Asia–Pacific region.

Background: In Taiwan, there were only 799 confirmed COVID-19 cases in 2020. The unique backdrop amidst a pandemic and promotion of nonpharmaceutical interventions generated some distinct changes in the epidemiology of common respiratory pathogens. In this study, we aimed to investigate the dynamic changes in respiratory pathogens in children during 2020. Methods: We performed a retrospective cohort study at a tertiary hospital in southern Taiwan during 2020. Patients aged 0–18 years who visited the pediatric emergency department were enrolled. Children who presented with clinical symptoms (fever or respiratory illness) and received nasopharyngeal swabs for multiplex polymerase chain reaction (PCR) were included in our analysis. We also compared respiratory syncytial virus (RSV) trends from previous years by PCR and lateral flow immunochromatographic assays from 2017 to 2020. Results: A total of 120 children were tested. The overall detection rate was 55%. With strengthened restrictions, the detection rate dropped from 70% to 30%. However, non-enveloped viruses (rhinovirus/enterovirus and adenovirus) were in constant circulation. Upon easing prevention measures, the detection rate remained above 60%, and an outbreak of an enveloped virus (RSV and parainfluenza virus) was noted. Compared with 2017–2019, the cyclical RSV epidemic was delayed, with a large surge in late 2020. Conclusions: We observed a constant circulation of non-enveloped viruses when strict nonpharmaceutical interventions were employed and a delayed surge of enveloped viruses during the easing of restrictions. Continuous surveillance and monitoring of the evolutionary dynamics of respiratory viruses is important, while easing restrictions requires balanced judgment.

Objectives: This study investigated the clinical efficacy and safety of oral Janus kinase inhibitors (JAKis) in the treatment of hospitalized patients with COVID-19. Methods: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before January 29, 2022. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of oral JAKis in patients with COVID-19 were included. Results: In the pooled analysis of the 7 RCTs, the all-cause 28-day mortality rate in the study group receiving JAKis was significantly lower than that in the control group (9.4% [183/1941] vs. 10.9% [184/1687], risk ratio [RR] = 0.69, 95% confidence interval [CI], 0.58–0.81, I2 = 0%). In addition, the risk of 14-day mortality was in the study group was lower than that in the control group (RR = 0.65, 95% CI, 0.46–0.92, I2 = 0%). Finally, the study group and the control group exhibited similar risks of any adverse events (RR = 0.96, 95% CI, 0.89–1.04, I2 = 0%). Conclusions: Oral JAKis can significantly reduce the risk of death among patients with COVID-19. In addition, JAKis are tolerable for hospitalized patients with COVID-19.

Shigellosis appears to increase in certain at-risk populations in developed countries. Based on the nationwide surveillance, the annual incidence of shigellosis in Taiwan (1999-2019) was 0.38-5.77 cases per 100,000 people. Indigenous shigellosis has mostly affected men who have sex with men (MSM) and people living with HIV (PLWH) since 2015. In this retrospective study, compared with those diagnosed before 2015, indigenous cases diagnosed during 2015–2019 mostly occurred in male adults (96.0% vs 47.1%, P

Candida auris, a multidrug resistant pathogenic yeast, has spread worldwide and caused several outbreaks in healthcare settings. Here, we report the first case of C. auris candidemia in Taiwan in a patient with a two-month history of hospitalization in Vietnam. We performed further investigation on the isolate from the present case as well as the previously reported C. auris isolate identified from a wound in 2018 in Taiwan, which was the first case reported in Taiwan. Both C. auris isolates were found to be susceptible to fluconazole, amphotericin B, and echinocandins. Additionally, mutations in ERG11 or FKS1 were not detected in either isolate. Microsatellite genotyping revealed that both isolates belonged to the South Asian clade. In recent years, C. auris has emerged as a global concern, and differences in clades and susceptibility patterns mandate further awareness and systematic surveillance.

Background/purpose: This study aimed to investigate the in vitro susceptibilities of carbapenem-non-susceptible Pseudomonas aeruginosa (CNSPA) and Acinetobacter baumannii (CNSAB) isolates to cefiderocol, novel β-lactamase inhibitor (BLI) combinations, new tetracycline analogues, and other comparative antibiotics. Methods: In total, 405 non-duplicate bacteremic CNSPA (n = 150) and CNSAB (n = 255) isolates were collected from 16 hospitals in Taiwan between 2018 and 2020. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibilities were interpreted according to the relevant guidelines or in accordance with results of previous studies and non-species-related pharmacokinetic/pharmacodynamic data. Results: Among the isolates tested, cefiderocol demonstrated potent in vitro activity against CNSPA (MIC50/90, 0.25/1 mg/L; 100% of isolates were inhibited at ≤4 mg/L) and CNSAB (MIC50/90, 0.5/2 mg/L; 94.9% of isolates were inhibited at ≤4 mg/L) isolates. More than 80% of CNSPA isolates were susceptible to cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and amikacin, based on breakpoints established by the Clinical and Laboratory Standards Institute. Activities of new BLI combinations varied significantly. Tetracycline analogues, including tigecycline (MIC50/90, 1/2 mg/L; 92.5% of CNSAB isolates were inhibited at ≤2 mg/L) and eravacycline (MIC50/90, 0.5/1 mg/L; 99.6% of CNSAB isolates were inhibited at ≤2 mg/L) exhibited more potent in vitro activity against CNSAB than omadacycline (MIC50/90, 4/8 mg/L). Conclusions: The spread of CNSPA and CNSAB poses a major challenge to global health. Significant resistance be developed even before a novel agent becomes commercially available. The development of on-site antimicrobial susceptibility tests for these novel agents is of great clinical importance.

ObjectivesTo investigate the in vitro activity of antibiotic combinations against Stenotrophomonas maltophilia isolates and their associated biofilms.MethodsThirty-two S. maltophilia clinical isolates with at least twenty-five different pulsotypes were tested. The antibacterial activity of various antibiotic combinations against seven randomly selected planktonic and biofilm-embedded S. maltophilia strains with strong biofilm formation was assessed using broth methods. Extraction of bacterial genomic DNA and PCR detection of antibiotic resistance and biofilm-related genes were also performed.ResultsThe susceptibility rates of levofloxacin (LVX), fosfomycin (FOS), tigecycline (TGC) and sulfamethoxazole-trimethoprim (SXT) against 32 S. maltophilia isolates were 56.3, 71.9, 71.9 and 90.6%, respectively. Twenty-eight isolates were detected with strong biofilm formation. Antibiotic combinations, including aztreonam-clavulanic (ATM-CLA) with LVX, ceftazidime-avibactam (CZA) with LVX and SXT with TGC, exhibited potent inhibitory activity against these isolates with strong biofilm formation. The antibiotic resistance phenotype might not be fully caused by the common antibiotic-resistance or biofilm-formation gene.ConclusionS. maltophilia remained resistant to most antibiotics, including LVX and β-lactam/β-lactamases; however, TGC, FOS and SXT still exhibited potent activity. Although all tested S. maltophilia isolates exhibited moderate-to-strong biofilm formation, combination therapies, especially ATM-CLA with LVX, CZA with LVX and SXT with TGC, exhibited a higher inhibitory activity for these isolates.

ABSTRACT Data regarding the durability of tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) in maintaining hepatitis B virus (HBV) viral suppression among HIV/HBV-coinfected patients are limited. Between February and October 2018, 274 HIV/HBV-coinfected participants who had achieved HIV RNA of

Background: Atherosclerosis and vascular inflammatory response have been considered as risk factors for non-typhoidal Salmonella (NTS) vascular infection. The study aims to assess the risk of vascular infection by measuring atherosclerosis severity, NTS vascular infection (NTSVI) score, and serum levels of inflammatory markers in people with NTS bacteremia. Methods: A prospective observational study was conducted in two medical centers and two regional hospitals. Adults aged ≥50 years with NTS bacteremia who underwent computed tomography (CT) scan for revealing vascular infections were enrolled. The degree of atherosclerosis was scaled by a calcium score determined by a CT scan. Serum concentrations of inflammatory biomarkers were determined in the patients enrolled in a medical center. Results: Fourteen (20.3%) of 69 patients with NTS bacteremia had vascular infections. Calcium scores over the thoracic (12,540 vs. 3,261, P = 0.0005) and abdominal (9755 vs. 3,461, P = 0.0006) aorta of those with vascular infections were higher than those without vascular infection. All vascular infections were present in the high-risk group (NTSVI score ≥1), yielding a sensitivity of 100% and specificity of 30.9%. Among 17 low-risk patients (NTSVI score

BackgroundPeople living with HIV (PLWH) have an increased risk of developing cardiovascular diseases (CVD). As speckle-tracking echocardiography (STE) has been used to detect subclinical myocardial abnormalities, this study aims to detect early cardiac impairment among Asian PLWH using STE and to investigate the associated risk factors.MethodsWe consecutively recruited asymptomatic PLWH without previous CVD from a medical center of Taiwan, and their cardiac function was evaluated by conventional echocardiogram and STE. Enrolled PLWH were classified as antiretroviral therapy (ART)-experienced and ART-naive, and multivariable regressions were used to assess the association between myocardial strain and risk factors including traditional CVD and HIV-associated factors.ResultsA total of 181 PLWH (mean age: 36.4 ± 11.4 years, 173 males) were recruited and conventional echocardiogram parameters were within normal ranges. Decreased myocardial strain across the myocardium was found, with a mean left ventricular (LV) global longitudinal strain of −18.7 ± 2.9%. The LV strain in the ART-experienced group (−19.0 ± 2.9%) was significantly better than the ART-naive group (−17.9 ± 2.8%), despite a younger age and lesser CVD risk factors in the ART-naive group. Hypertension [B = 1.92, 95% confidence interval (95% CI) 0.19–3.62, p = 0.029] and ART-naive with both low and high viral loads (VL) (B = 1.09, 95% CI 0.03–2.16, p = 0.047; and B = 2.00, 95% CI, 0.22–3.79, p = 0.029) were significantly associated with reduced myocardial strain.ConclusionThis is the first and largest cohort using STE to investigate myocardial strain in Asian PLWH. Our results suggest that hypertension and detectable VL are associated with impaired myocardial strain. Thus, timely ART administration with VL suppression and hypertension control are crucial in preventing CVD when making the management parallel with the improved life expectancy of PLWH on ART.

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/Purpose: Accurate identification of Candida species is increasingly important in the era of emergence of Candida auris. We aimed to compare the identification performance of two matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems (Vitek MS and Bruker biotyper MS) and an oligonucleotide array for uncommon blood yeast isolates and demonstrate the susceptibilities among those isolates. Method: Candida species isolates from blood culture other than Candida albicans, Candida parapsilosis, Candida tropicalis, Candida glabrata, and Candida krusei identified by biochemical methods were collected from multiple hospitals and further identified by an oligonucleotide array based on the internal transcribed spacer-1 (ITS-1) and ITS-2 sequences of the rRNA genes, Vitek MS and Bruker biotyper MS. The minimal inhibitory concentrations (MICs) of these clinical isolates were determined by the Sensititre YeastOne (SYO) system. Results: Among 136 isolates, Candida guilliermondii was most common (52, 38.2%), followed by C. lusitaniae (13, 9.6%) and C. haemulonii (12, 8.8%). The oligonucleotide array, Vitek MS and Bruker biotyper MS correctly identified 89.7% (122), 90.4% (123), and 92.6% (126) of these isolates, respectively. Elevated minimal inhibitory concentrations (MICs) of fluconazole were observed for C. haemulonii (MIC90: 256 mg/L), and C. guilliermondii (MIC90: 16 mg/L) with 28.4% of uncommon Candida isolates with MIC ≧ 8 mg/L. Conclusions: For uncommon Candida species, the unmet need for current databases of two commercial MALDI-TOF MS systems is highlighted, and the oligonucleotide array may serve as a supplement.

ObjectivesThis study investigated the inhibitory effect of Lactobacillus spp. with prebiotics against Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing Klebsiella pneumoniae using both in vitro experiments and animal models.MethodsThirty-three Lactobacillus spp. strains were confirmed by 16S rDNA sequencing, and four different PFGE genotyped KPC-2-producing K. pneumoniae strains were selected for investigation. In vitro studies, including broth microdilution assays, changes in pH values in lactobacilli cultures with different prebiotics, time-kill tests of Lactobacillus spp. against KPC-2-producing K. pneumoniae and further in vivo Lactobacillus alone or in combination with prebiotics against KPC-2-producing K. pneumoniae in an animal model, were performed.ResultsThe lower pH value of the cell-free supernatant was associated with a lower minimal inhibitory percentage of the Lactobacillus strain against KPC-2-producing K. pneumoniae. Furthermore, lactulose/isomalto-oligosaccharide/inulin and fructo-oligosaccharide can enhance the inhibitory effect of all 107 CFU/ml Lactobacillus strains against KPC001. Three Lactobacillus strains (LYC1154, LYC1322, and LYC1511) that could be persistently detected in the stool were tested for their ability to reduce the amount of KPC001 in the feces individually or in combination. A significantly better effect in reducing the amount of KPC001 was observed for the combination of three different Lactobacillus species than for each of them alone. Furthermore, their inhibitory effect was enhanced after adding lactulose or isomalto-oligosaccharide (both p

Background: This study aims to investigate the antimicrobial ability and mechanism analysis of Lactobacillus species against carbapenemase-producing Enterobacteriaceae (CPE). Methods: Five Lactobacillus spp. strains and 18 CPE clinical isolates were collected. Their anti-CPE effects were assessed by agar well diffusion and broth microdilution assay, as well as time-kill test. Finally, the specific anti-CPE mechanism, especially for the effect of organic acids was determined using broth microdilution method. Results: All of five Lactobacilli isolates displayed the potent activity against most CPE isolates with mean zones of inhibition ranging 10.2–21.1 mm. The anti-CPE activity was not affected by heating, catalase, and proteinase treatment. Under the concentration of 50% LUC0180 cell-free supernatant (CFS), lactic acid, and mix acid could totally inhibit the growth of carbapenem-resistant Klebsiella pneumoniae (CPE0011), and acetic acid could inhibit 67.8%. In contrast, succinic acid and citric acid could not inhibit the growth of CPE0011. While we decreased the concentration to 25%, only lactic acid and mix acid displayed 100% inhibition. In contrast, succinic acid, citric acid and acetic acid did not show any inhibitory effect. Conclusions: Lactobacillus strains exhibit potent anti-CPE activity, and lactic acid produced by Lactobacillus strains is the major antimicrobial mechanism.

We report 4 cases of neonatal sepsis caused by Streptococcus gallolyticus. The clinical course was quite similar to early-and late-onset group B streptococcus disease. None of the mothers had group B streptococcus (GBS) colonization on prenatal screening nor received intrapartum antibiotics. We proposed the sporadic distribution of S. gallolyticus sepsis among neonates was partly due to relatively low colonization rate in adults compared with GBS. Species determination of S. gallolyticus may not be available using conventional microbiological methods and may contribute to underestimation or misclassification. In our series, we highlighted the importance of S. gallolyticus as an important pathogen in neonatal sepsis deserving further surveillance.

Background/purpose: This multicenter study aimed to evaluate the seroprevalence of hepatitis B virus (HBV) and the use of combination antiretroviral therapy (cART) among patients receiving HIV care in Taiwan. Methods: We retrospectively reviewed the medical records of HIV-infected adult patients who initiated cART at 11 designated hospitals in Taiwan between 2012 and 2016. The clinical information collected included serological profiles on HBV, hepatitis C virus (HCV), and syphilis, plasma HIV RNA load, nadir CD4 cell count, and antiretrovirals with activity against both HBV and HIV (tenofovir disoproxil fumarate [TDF], lamivudine [LAM], and emtricitabine [FTC]). Results: We analyzed 1800 HIV-infected patients; 1742 (96.8%) were male and 794 (44.1%) were born after July, 1986, when nationwide universal neonatal HBV vaccination was implemented. HBsAg positive results were 11.6% (209/1800), which decreased significantly from 18.1% (182/1006) in those born before July 1986 to 3.4% (27/794) in those born after. In multivariable analysis, HBsAg positivity was significantly associated with age (adjusted odds ratio [aOR] 1.06, 95% confidence interval [CI] 1.05–1.08), CD4≧200 cells/μL (aOR 0.73, 95% CI 0.53–0.99), and HCV seropositivity (aOR 1.62, 95% CI 1.06–2.50). Of 209 HBV/HIV-coinfected patients, 31.1% started cART containing only LAM with anti-HBV activity, while 68.9% started cART containing TDF plus LAM or coformulated TDF/FTC. Conclusions: The overall prevalence of HBV/HIV coinfection remained high among HIV-infected patients in Taiwan. Despite recommendations of the HIV treatment guidelines for the management of HBV infection, a substantial proportion of HIV/HBV-coinfected patients received cART containing only LAM for HBV infection.

Background/Purpose: The 2009 WHO guideline established warning signs (WS) to predict severe dengue (SD). However, their positive predictive value has been found to be low in the general adult population, but they might be higher in a different population. This study investigated the association between WS and SD in end stage renal disease (ESRD) patients on maintenance dialysis in Taiwan where both diseases are prevalent. Methods: This study enrolled ESRD dialysis patients with dengue in 2015. Demographic, laboratory data, symptoms/signs and complication of dengue were retrospectively collected from medical records at our hospital. Results: Of 49 ESRD patients with dengue, 44 patients were receiving hemodialysis and 5 peritoneal dialysis. Older patients (>65 years old) tended to have the WS(56% vs 16.7%, P = 0.007). The rate of hospitalization, intensive care unit admission and in-hospital mortality was 79.6%, 22.5%, and 8.2%, respectively. Eighteen patients (36.7%) presented WS and eighteen patients (36.7%) developed to SD, including ten with plasma leakage, twelve with hemorrhage, and six with organ failure. Patients with WS were seven times more likely to develop SD than those without (OR: 7.06; 95%CI: 1.34–37.21). WS was associated with plasma leakage (OR: 12.36; 95% CI: 1.56–97.74) and severe hemorrhage (OR: 5.1; 95% CI: 1.03–25.18), but not organ failure. Conclusions: Prevalence of SD is high in ESRD dialysis patients. The presence of WSs in this group was highly correlated with SD. Thus, more attention should be paid to treating ESRD patients with dengue fever if they present WSs.

Aeromonas dhakensis is an emerging human pathogen which causes fast and severe infections worldwide. Under the gradual pressure of lacking useful antibiotics, finding a new strategy against A. dhakensis infection is urgent. To understand its pathogenesis, we created an A. dhakensis AAK1 mini-Tn10 transposon library to study the mechanism of A. dhakensis infection. By using a Caenorhabditis elegans model, we established a screening platform for the purpose of identifying attenuated mutants. The uvrY mutant, which conferred the most attenuated toxicity toward C. elegans, was identified. The uvrY mutant was also less virulent in C2C12 fibroblast and mice models, in line with in vitro results. To further elucidate the mechanism of UvrY in controlling the toxicity in A. dhakensis, we conducted a transcriptomic analysis. The RNAseq results showed that the expression of a unique hemolysin ahh1 and other virulence factors were regulated by UvrY. Complementation of Ahh1, one of the most important virulence factors, rescued the pore-formation phenotype of uvrY mutant in C. elegans; however, complementation of ahh1 endogenous promoter-driven ahh1 could not produce Ahh1 and rescue the virulence in the uvrY mutant. These findings suggest that UvrY is required for the expression of Ahh1 in A. dhakensis. Taken together, our results suggested that UvrY controls several different virulence factors and is required for the full virulence of A. dhakensis. The two-component regulator UvrY therefore a potential therapeutic target which is worthy of further study.

Objectives: We assessed the economic burden of AIDS-defining illnesses (ADIs), which was further stratified by adherence to antiretroviral therapy (ART). Methods and materials: A nationwide longitudinal cohort of 18,234 incident cases with HIV followed for 11 years was utilized. Adherence to ART was measured by medication possession ratio (MPR). Generalized estimating equations modeling was used to estimate the cost impact of ADIs. Results: Having opportunistic infections increased the annual cost by 9% (varicella-zoster virus infection) to 98% (cytomegalovirus disease), while the annual costs increased by 26% (Kaposi’s sarcoma) to 95% (non-Hodgkin’s lymphoma) in the year when AIDS-related cancer occurred. ADIs occurred more frequently in the years with low adherence for ART compared to the high-adherence years (e.g., 0.1 ≤ MPR

BackgroundCOVID-19 vaccination is essential. However, no study has reported adverse events (AEs) after ChAdOx1 nCoV-19 vaccination in patients with end-stage renal disease (ESRD) on hemodialysis (HD). This study investigated the AEs within 30-days after the first dose of ChAdOx1 nCoV19 (Oxford-AstraZeneca) in ESRD patients on HD.Methods and findingsA total of 270 ESRD patients on HD were enrolled in this study. To determine the significance of vascular access thrombosis (VAT) post vaccination, we performed a self-controlled case study (SCCS) analysis. Of these patients, 38.5% had local AEs; local pain (29.6%), tenderness (28.9%), and induration (15.6%) were the most common. Further, 62.2% had systemic AEs; fatigue (41.1%), feverishness (20%), and lethargy (19.9%) were the most common. In addition, post-vaccination thirst affected 18.9% of the participants with female predominance. Younger age, female sex, and diabetes mellitus were risk factors for AEs. Five patients had severe AEs, including fever (n = 1), herpes zoster (HZ) reactivation (n = 1), and acute VAT (n = 3). However, the SCCS analysis revealed no association between vaccination and VAT; the incidence rate ratio (IRR)-person ratio was 0.56 (95% CI 0.13-2.33) and 0.78 (95% CI 0.20-2.93) [IRR-event ratio 0.78 (95% CI 0.15-4.10) and 1.00 (95% CI 0.20-4.93)] in the 0-3 months and 3-6 months period prior to vaccination, respectively.ConclusionsThough some ESRD patients on HD had local and systemic AEs after first-dose vaccination, the clinical significance of these symptoms was minor. Our study confirmed the safety profile of ChAdOx1 nCoV-19 in HD patients and presented a new viewpoint on vaccine-related AEs. The SCCS analysis did not find an elevated risk of VAT at 1 month following vaccination. Apart from VAT, other vaccine-related AEs, irrespective of local or systemic symptoms, had minor clinical significance on safety issues. Nonetheless, further coordinated, multi-center, or registry-based studies are needed to establish the causality.

Background: In Southeast Asia, Japanese encephalitis (JE) is an important cause of viral encephalitis which may cause severe neurological sequelae. JE affects mostly children; therefore, clinical presentations and prognosis of adult JE patients are seldom addressed. This study aimed to describe the clinical characteristics and prognostic factors for the outcome of adult JE patients. Methods: Medical records of adult JE patients with acute encephalitis syndrome during 2001–2018 from five medical centers in southern Taiwan were reviewed. Clinical characteristics, brain images, and prognostic factors for outcomes were analyzed. Patients were divided into the good outcome (GO) group and poor outcome (PO) group according to their Glasgow Coma Scale (GCS) scores (GCS >8 vs. ≤ 8) at discharge. Results: Sixty-eight patients (men, 61.8%; median age, 50 years) were included. Summer is the epidemic season, and the number of cases peaked in June. The most common symptoms at initial presentation were altered consciousness and fever (both 94.1%), followed by headache (51.4%). The most commonly involved brain regions were thalamus (55.7%) and basal ganglion (37.7%). The median GCS score at nadir was 8, and the median time from onset to nadir was five days. Fifty-two patients were included in the GO group, while 16 were included in the PO group. On multivariate analysis, flaccidity, rigidity, and elevated CSF protein level were identified as independent prognostic factors for PO. Conclusion: Initial clinical presentations of abnormal muscle tone including flaccidity, rigidity and high CSF protein levels are independent prognostic factors for PO in adult JE patients. Keywords: Adult, Japanese encephalitis, Outcome, Prognostic factor

Abstract Background Bloodstream infections are associated with high morbidity and mortality, both of which contribute substantially to healthcare costs. The effects of early administration of appropriate antimicrobials on the prognosis and timing of defervescence of bacteremic patients remain under debate. Methods In a 6-year retrospective, multicenter cohort, adults with community-onset bacteremia at the emergency departments (EDs) were analyzed. The period from ED arrival to appropriate antimicrobial administration and that from appropriate antimicrobial administration to defervescence was regarded as the time-to-appropriate antibiotic (TtAa) and time-to-defervescence (TtD), respectively. The primary study outcome was 30-day mortality after ED arrival. The effects of TtAa on 30-day mortality and delayed defervescence were examined after adjustment for independent predictors of mortality, which were recognized by a multivariate regression analysis. Results Of the total 3194 patients, a TtAa-related trend in the 30-day crude (γ = 0.919, P = 0.01) and sepsis-related (γ = 0.909, P = 0.01) mortality rate was evidenced. Each hour of TtAa delay was associated with an average increase in the 30-day crude mortality rate of 0.3% (adjusted odds ratio [AOR], 1.003; P 24 h) on the TtD was noted, regardless of bacteremia severity, bacteremia sources, or causative microorganisms. Conclusions The delay in the TtAa was associated with an increasing risk of delayed defervescence and 30-day mortality for adults with community-onset bacteremia, especially for critically ill patients. Thus, for severe bacteremia episodes, early administration of appropriate empirical antimicrobials should be recommended.

Background/purpose: Acute HIV infection is characterized by a high concentration of HIV RNA in the plasma and rapid depletion of the CD4 cell count. This multicenter, retrospective observational study aimed to characterize the manifestations of acuteHIV infection in Taiwan. Methods: Between 1 January 2012 and 31 December 2016, all patients aged 20 years or greater who presented with acute HIV infection were included. Demographic and clinical characteristics of the patients at diagnosis were collected. Baseline laboratory assessment included hemogram, CD4 count, plasma HIV RNA load (PVL), serologic markers of syphilis and hepatitis A, B, and C viruses, and serum biochemistry. Results: The proportion of acute HIV infection was 6.9% among the patients with newly diagnosed HIV infection during the study period. The most common presenting symptoms of acute HIV infection were fever, fatigue, and myalgia. The median PVL at diagnosis was 5.9 log10 copies/ml, and median CD4 count was 307 cells/mm3. A total of 68 patients (27%) had baseline CD4 count less than 200 cells/mm3. Multiple logistic regression analysis, showed that the baseline CD4 count (OR, 4.02; p = 0.013) and aspartate aminotransaminase levels (OR, 3.49; p = 0.002) were associated with high PVL (>5 log10 copies/ml); and high baseline PVL (OR, 2.64; p = 0.002) was associated with symptomatic acute HIV infection. Conclusions: Manifestations of acute HIV infection are nonspecific and of wide spectrum ranging from fever to severe illness. A higher proportion of patients with initial CD4 counts of 200 cells/mm3 or less during acute HIV infection warrants early, timely diagnosis and treatment to prevent rapid disease progression. Keywords: Acute HIV infection, Aseptic meningitis, Combination antiretroviral therapy, Fiebig stage, Infectious mononucleosis

Objective: This retrospective study investigated clinical manifestations of candidemia caused by uncommon Candida species and antifungal susceptibility of the isolates in a regional hospital in Taiwan. Methods: The uncommon Candida species was initially defined as Candida species other than C. albicans, C. tropicalis, C. glabrata complex, C. parapsilosis complex and C. krusei. All uncommon Candida isolates were identified and confirmed by molecular methods. In vitro susceptibility testing of the uncommon Candida species to nine antifungal agents was conducted using the broth microdilution method with the Sensititre YeastOne (SYO) system (Trek Diagnostic Systems, Ltd., East Grimstead, UK). Results: Twenty-one patients, comprising 11 males and 10 females with a median age of 69 years, were recruited. Cancer (n = 11) was the most common underlying disease, 19 (90.5%) cases had prior antibiotic exposure, and only two patients had prior antifungal use. The overall in-hospital mortality rate was 38.1% (n = 8). C. guilliermondii (n = 11) was the most common pathogen, followed by C. curvata (n = 3). C. guilliermondii isolates exhibited relatively high rates of azole minimum inhibitory concentrations (MICs) above epidemiological cut-off values (ECVs), whereas C. pelliculosa and C. lusitaniae isolates all remained susceptible to azoles. All three C. curvata isolates had high caspofungin (>8 mg/L) and fluconazole MICs (8 mg/L) and could be defined as multidrug-resistant. Conclusions: Uncommon Candida species frequently exhibit high rates of non-susceptibility to antifungals. Identification of all Candida isolates at the species level from blood samples is of value for treatment. Keywords: Candidemia, Uncommon candida species, Healthcare-associated infection, Antifungal susceptibility testing, Azoles, Echinocandin

Background: Dengue is an important mosquito-borne tropical viral disease and dual infection, though rare, has been regarded as a risk factor for severe disease and mortality. However, few studies focused on bloodstream infections (BSIs) and empirical antibiotic therapy rarely addressed. Methods: Dengue patients with concurrent or subsequent BSIs between July 1 and December 31, 2015 were included. Clinical information, laboratory data, and drug susceptibility data were collected. Results: Totally 80 patients, with an in-hospital mortality rate of 32.5%, were included and categorized into three groups. 32 patients in Group I (BSI onset within 48 h after admission), 32 in Group II (between 48 h and one week), and 16 in Group III (more than one week). Patients in Group I were older (mean age: 75.6 vs. 72.6 or 69.6 years; P = 0.01) and had a higher Charlson comorbidity index (3.1 vs. 1.8 or 1.9; P = 0.02) than those in Group II or III. Streptococcus species (28.9%, 11/38) and Escherichia coli (23.7%, 9/38) were major pathogens in Group I. Enterobacteriaceae (38.2%, 13/34) isolates predominated in Group II. Fatal patients more often received inappropriate empirical antibiotic than the survivors (61.5% vs. 35.2%; P = 0.03). According to susceptibility data, pathogens in Group I and II shared similar susceptibility profiles, and levofloxacin, cefepime, or piperacillin/tazobactam, can be empirically prescribed for those hospitalized within one week. Conclusions: BSI pathogens vary among dengue patients. For adults with dengue and suspected BSI hospitalized within one week, empirical antimicrobial agents are recommended. Keywords: Severe dengue, Sepsis, Bacteremia, Candidemia, Empirical therapy, Concurrent infection, Fatality

Background/Purpose: In vitro studies of the combination of an aminoglycoside with tigecycline or doxycycline against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates are rarely published. The goal of this study was to evaluate the antibacterial activity of the combination regimens. Methods: Thirteen genetically different KPC-producing K. pneumoniae isolates were randomly selected. Drug concentrations of amikacin, gentamicin, tigecycline, and doxycycline were adjusted to 1-, 1/2-, and 1/4-fold of respective minimum inhibitory concentrations (MICs). Each drug alone or the combinations of amikacin or gentamicin with tigecycline or doxycycline were tested by combination studies. Results: Treatment with the 1× MIC concentration in combinations of amikacin or gentamicin and tigecycline or doxycycline for 24 hours resulted in bactericidal activity of 84–100% in the isolates. Treatment with 1/2× MIC combinations resulted in synergism of 69–100% in the isolates. Notably, doxycycline plus gentamicin or amikacin was synergistic for all tested isolates. However, bactericidal or synergistic effect was barely evident following 1/4× MIC combinations. There was no antagonism in any of the combination regimens. Conclusion: Enhanced activity was noted following treatment with doxycycline combined with gentamicin or amikacin against KPC-producing K. pneumoniae isolates, warranting further in vitro and animal investigations before clinical application. Keywords: aminoglycoside, doxycycline, KPC, synergism, tigecycline

Background/purpose: This study investigated the cause of hand hygiene deficit, and further implemented a quality improvement program using WHO's hand-hygiene strategy to enhance the compliance of hand hygiene in the nursing home in Taiwan. Methods: This prospective study was conducted in eleven nursing homes in Taiwan from January 2015 to December 2016. After intervention, we monitor the compliance, and accuracy of hand hygiene. In addition, we also calculated the number of episodes of infection per 1000 resident-days in each nursing home in the intervention period (July–December 2015) and post-intervention period (January–October 2016). Results: Overall, the consumption of alcohol-based handrubs increased from 10.1 ml per resident-day in intervention period to 12.2 ml per resident-day in post intervention period. The compliance of hand hygiene increased from 74% in intervention period to 79% in post-intervention period and the rate of correct hand hygiene increased from 81% in intervention period to 87% in post-intervention period. Most importantly, the infection density decreased from 2.39 per 1000 resident-day in intervention period to 1.89 per 1000 resident-day. Conclusions: A national quality-improvement program using WHO's hand-hygiene strategy to enhance hand hygiene and reduce healthcare associated infection is effective in nursing homes in Taiwan. Keywords: Quality improvement program, Hand hygiene, Nursing homes, Taiwan

Background/purpose: Globally, multidrug-resistant Acinetobacter baumannii (MDRAB) has emerged as an important pathogen in nosocomial outbreaks. This study aimed to investigate the correlation between the biofilm formation and survival of MDRABs, and to investigate the antiseptic efficacy of hand sanitizers for the MDRABs, embedded with biofilm (MDRAB-Bs). Methods: The MDRABs were selected randomly after pulsed-field gel electrophoresis (PFGE), and their biofilm formation was analyzed. Desiccation and ethanol tolerances were assayed to test the bacterial survival. The antiseptic efficacy of combined chlorhexidine gluconate (CHG) and 70% ethanol agents against MDRAB-Bs were compared with the 70% ethanol cleanser. Results: Eleven MDRABs, which varied in biofilm formation (MRDAB-B) and planktonic type (MDRAB-P), were tested. In desiccation survival, the mean survival time for the MDRAB-Bs was 49.0 days which was significantly higher than that of their planktonic type (17.3 days) (P

The optimal dosage of cefoperazone-sulbactam for patients with chronic kidney disease (CKD) remains unclear. This study aimed to investigate two treatment strategies of cefoperazone-sulbactam–2 g/2 g twice daily and adjusted dose according to renal function for patients with CKD. A total of 155 patients with CKD received cefoperazone-sulbactam either at a dose of 2 g/2 g twice daily (study group) or adjusted according to renal function (control group) for the treatment of acute bacterial infection. The primary outcome was the clinical response rate at day 14 and the secondary outcomes included treatment failure and all-cause death. The study group had a higher clinical response rate (80.0% vs. 65.0%) and a lower treatment failure rate (4.0% vs. 23.8%) as compared with the control group. Further multivariable analysis showed that compared with the control group, the study group had a higher clinical response rate (adjusted OR = 4.02; 95% CI, 1.49–10.81) and lower treatment failure rate (adjusted OR = 0.06; 95% CI, 0.01–0.28). In addition, no significant difference in all-cause mortality was observed between the study and the control group (adjusted OR = 1.95; 95% CI, 0.57–6.66). Finally, no significant difference was observed between the study and the control group in the risk of the adverse events (AEs)–diarrhea (p = 0.326), eosinophilia (p = 1.000), prolonged PT (p = 0.674), alteration in renal function (p = 0.938) and leukopenia (n = 0.938). In conclusion, cefoperazone-sulbactam at a dose of 2 g/2 g twice daily could achieve better clinical efficacy than the reduced dosage regimen. Additionally, this dosage did not increase the risk of AE compared to the reduced dose. Therefore, cefoperazone-sulbactam at a dose of 2 g/2 g twice daily is an effective and safe regimen for acute bacterial infection in patients with CKD.

This study was conducted to compare the number of cases of airborne/droplet-transmitted notifiable infectious disease (NID) between the pandemic period (defined as from January 2020 to December 2021) and the pre-pandemic period (defined as the period from January 2018 to December 2019). The annual case numbers of airborne/droplet-transmitted NIDs from 2018 to 2021 were collected for comparison. Fourteen airborne/droplet-transmitted NIDs including measles, rubella, pertussis, influenza with severe complications, invasive pneumococcal diseases (IPD), Q fever, mumps, meningococcal meningitis, varicella, legionellosis, invasive Haemophilus influenzae type b infection, hantavirus syndrome, TB, and multidrug-resistant TB (MDRTB), were included for the analysis. Overall, the annual case number of these 14 airborne/droplet-transmitted NID was 11,930, 12,747, 9477, and 8268 in 2018, 2019, 2020, and 2021, respectively, and the overall incidence was 50.3, 53.6, 39.8, 34.6 per 100,000 populations in in 2018, 2019, 2020, and 2021. The case number of influenza with severe complications had the largest reduction from the pre-pandemic period to the pandemic period, with a reduction of 3076 cases, followed by TB (−2904), IPD (−490), mumps (−292), measles (−292), pertussis (−57), MDRTB (−43), rubella (−35), Q fever (−20), varicella (−12), meningococcal meningitis (−5), invasive H. influenzae type B (−4). In contrast, the case number of legionellosis increased from 492 during the pre-pandemic period to 676 during the pandemic period. In addition, hantavirus syndrome also increased from zero cases during the pre-pandemic period to three during the pandemic period. In conclusion, the occurrence of most airborne/droplet-transmitted NIDs, including both domestic and imported cases in Taiwan, was lower during the pandemic period than during the pre-pandemic period.

This study aimed to compare clinical outcomes and adverse effects in septic patients with impaired renal function who received different dosages of cefoperazone–sulbactam (CFP–SUL 1 g/1 g or 2 g/2 g every 12 h). The retrospective study was conducted using the Chang Gung Research Database to include adult patients who had renal insufficiency presented with septicemia caused by Gram-negative organisms and had received CFP–SUL for more than 1 week. A total of 265 patients (44 in the CFP–SUL 1 g/1 g group and 221 in the CFP–SUL 2 g/2 g group) were eligible to be included in this study. After 1:3 propensity score matching, 41 and 123 patients in the CFP–SUL 1 g/1 g and CFP–SUL 2 g/2 g groups, respectively, were included for analyses. There were no significant between-group differences in all-cause mortality rates and adverse effects, including prolonged prothrombin time. A logistic regression model showed that the Pitt bacteremia score was related to all-cause mortality rate and prolonged prothrombin time was associated with renal replacement therapy. The adverse effects of CFP–SUL did not increase in septic patients with impaired renal function receiving CFP–SUL 2 g/2 g Q12H. However, this study may be underpowered to reveal a difference in all-cause mortality.

Matriptase plays important roles in epithelial integrity and function, which depend on its sorting to the basolateral surface of cells, where matriptase zymogen is converted to an active enzyme in order to act on its substrates. After activation, matriptase undergoes HAI-1-mediated inhibition, internalization, transcytosis, and secretion from the apical surface into the lumen. Matriptase is a mosaic protein with several distinct protein domains and motifs, which are a reflection of matriptase's complex cellular itinerary, life cycle, and the tight control of its enzymatic activity. While the molecular determinants for various matriptase regulatory events have been identified, the motif(s) required for translocation of human matriptase to the basolateral plasma membrane is unknown. The motif previously identified in rat matriptase is not conserved between the rodent and the primate. We, here, revisit the question for human matriptase through the use of a fusion protein containing a green fluorescent protein linked to the matriptase N-terminal fragment ending at Gly-149. A conserved seven amino acid motif EEGEVFL, which is similar to the monoleucine C-terminal to an acidic cluster motif involved in the basolateral targeting for some growth factors, has been shown to be required for matriptase translocation to the basolateral plasma membrane of polarized MDCK cells. Furthermore, time-lapse video microscopy showed that the motif appears to be required for entry into the correct transport vesicles, by which matriptase can undergo rapid trafficking and translocate to the plasma membrane. Our study reveals that the EEGEVFL motif is necessary, but may not be sufficient, for matriptase basolateral membrane targeting and serves as the basis for further research on its pathophysiological roles.

The outbreak of COVID-19 has significantly changed the epidemiology of respiratory tract infection in several ways. The implementation of non-pharmaceutical interventions (NPIs) including universal masking, hand hygiene, and social distancing not only resulted in a decline in reported SARS-CoV-2 cases but also contributed to the decline in the non-COVID-19 respiratory tract infection-related hospital utilization. Moreover, it also led to the decreased incidence of previous commonly encountered respiratory pathogens, such as influenza and Streptococcus pneumoniae. Although antimicrobial agents are essential for treating patients with COVID-19 co-infection, the prescribing of antibiotics was significantly higher than the estimated prevalence of bacterial co-infection, which indicated the overuse of antibiotics or unnecessary antibiotic use during the COVID-19 pandemic. Furthermore, inappropriate antimicrobial exposure may drive the selection of drug-resistant microorganisms, and the disruption of infection control in COVID-19 setting measures may result in the spread of multidrug-resistant organisms (MDROs). In conclusion, NPIs could be effective in preventing respiratory tract infection and changing the microbiologic distribution of respiratory pathogens; however, we should continue with epidemiological surveillance to establish updated information, antimicrobial stewardship programs for appropriate use of antibiotic, and infection control prevention interventions to prevent the spread of MDROs during the COVID-19 pandemic.

Background: The presence of extended-spectrum β-lactamase (ESBL) in Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) is of great microbiological and clinical importance. The study dealing with the direct impact of ESBL producers on the outcome of patients with community-onset bacteremia is lacking. Methods: Adults with community-onset EKP bacteremia were recruited retrospectively during a 6-year period. ESBL producers were determined according to ESBL phenotype. ESBL patients were compared on a 1:2 basis with non-ESBL patients by using propensity-score matching (PSM) calculated based on independent predictors of 28-day mortality. Results: Of the 1141 eligible adult patients, 65 (5.7%) caused by ESBL producers. Significant differences between the two groups were discovered in the proportions of patients with critical illness (a Pitt bacteremia score ≥ 4) at bacteremia onset, inappropriate empirical antibiotic therapy, bacteremia because of urosepsis and pneumonia, and several comorbidities. In a PSM analysis after controlling for six independent predictors—critical illness at bacteremia onset, underlying fatal comorbidities (McCabe classification), inappropriate empirical antibiotic therapy, comorbidities with liver cirrhosis, bacteremia because of urosepsis and pneumonia—a appropriate matching between two groups (ESBL group, 60 patients; non-ESBL group, 120) were observed in age, causative microorganism, bacteremia severity, major comorbidities, comorbidity severity, and major bacteremia source. Consequently, a strong relationship between ESBL producers and poor prognosis was highlighted. Conclusions: The adverse influence of ESBL producers on clinical outcomes was presented with respect to adults with community-onset EKP bacteremia. Establishing a predictive scoring algorithm for identifying patients at risk of ESBL-producer infections is crucial. Keywords: Bacteremia, Extended-spectrum-β-lactamase, Escherichia coli, Klebsiella species, Proteus mirabilis

Background/Purpose: To investigate the clinical characteristics and pathogens of community-onset bacteremia among human immunodeficiency virus (HIV)-infected adults as well as to establish the clinical predictors of the major microorganisms. Methods: An observational cohort study was conducted retrospectively between January 2007 and December 2012. Demographic characteristics and pathogens determined from chart records were analyzed. Results: Of the 121 eligible HIV adults with bacteremia, there was a male predominance (106 patients, 87.6%); elderly individuals (age ≥ 65 years) accounted for only 2.5% of the study population (3 patients). Of the total microorganisms isolated (n = 123), Staphylococcus aureus (55, 44.7%) and Salmonella enterica (17, 13.8%) were the common pathogens. In a multivariate analysis, the leading two significant predictors of S. aureus infection were infective endocarditis (odds ratio, 11.49; p = 0.001) and transmission risk with injection drug users (IDUs; odds ratio, 6.22; p = 0.001). In addition, transmission risk with men who have sex with men (MSM; odds ratio, 37.49; p = 0.001) was the leading clinical predictor of S. enterica infection. In further analyses, a strong linear-by-linear correlation between S. aureus infection and IDU (γ = 0.94, p = 0.02) as well as between S. enterica infection and MSM (γ = 0.96, p = 0.01) was evidenced. Conclusion: Focusing on the two key pathogens in HIV-infected adults with community-onset bacteremia, IDU was one of independent predictors associated with S. aureus infection, whereas MSM was the leading risk factor of S. enterica infection. Although the proposed predictive model of these pathogens has been not established, a scoring system involving the transmission risk of HIV may be of use for the early identification of these patients for clinicians.