Background and Objectives: Cephalosporins containing N-hydroxyethyltetrazolethiol (HTT) or N-methylthiotetrazole (NMTT) side chains, such as flomoxef and cefoperazone, have been linked to coagulation abnormalities. Cefazolin, which contains an N-methylthiadiazolethiol (MTD) side chain, may also interfere with vitamin K metabolism. However, comparative clinical evidence remains limited. This study evaluated the associations between selected cephalosporins and coagulopathy risk. Materials and Methods: We conducted a retrospective cohort study using a comprehensive clinical database. Patients receiving cefazolin, flomoxef, or cefoperazone-sulbactam were compared with those receiving reference antibiotics. Coagulopathy was defined as either a ≥25% increase in prothrombin time (PT) from baseline or a PT exceeding the upper limit of normal by more than 3 s within three days before or after antibiotic cessation. Inverse probability of treatment weighting based on propensity scores was applied. Weighted logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: After weighting, no significant association with coagulopathy was observed for cefazolin (OR, 1.05; 95% CI, 0.86-1.29), flomoxef (OR, 1.00; 95% CI, 0.77-1.29), or cefoperazone-sulbactam (OR, 0.88; 95% CI, 0.67-1.15). Although international normalized ratio >1.2 was more frequent with cefoperazone-sulbactam, the risk of bleeding events showed a marginal increase compared with the reference group (OR, 1.06; 95% CI, 1.00-1.11). Conclusions: Cefoperazone-sulbactam was associated with more frequent laboratory INR elevation and a borderline increase in bleeding risk. Given the observational design, these findings should be interpreted cautiously, and close clinical monitoring may be considered when prescribing cefoperazone-sulbactam.

BACKGROUND:The epidemiology of tuberculosis in Taiwan has been influenced by the introduction of multiple Mycobacterium tuberculosis lineages and by the ageing of the population. We conducted a population-based study to investigate M tuberculosis transmission in Kaohsiung, a city in southern Taiwan. METHODS:In this study, we performed whole-genome sequencing (WGS) of M tuberculosis isolates from all culture-positive cases of tuberculosis notified in Kaohsiung between Jan 1, 2019 and Dec 31, 2023. We obtained routine epidemiological data for each case collected through the national tuberculosis control programme. We characterised the lineage composition of the isolate collection and evaluated genomic clustering of isolates, defined as a difference of 12 or fewer single-nucleotide polymorphisms. Univariable and multivariable logistic regression analyses were performed to estimate the odds of a case belonging to a genomic cluster based on host factors (age, sex, sputum smear status, and residential region) and pathogen factors (drug resistance status and strain lineage). Spatial aggregation of large genomic clusters (including greater than or equal to ten isolates) was assessed using a non-parametric statistical clustering method. We used a Bayesian transmission tree inference method to explore the patterns of age-dependent transmission. FINDINGS:During the study period, 5667 tuberculosis cases were notified in Kaohsiung, 4916 (86·7%) of which were culture-positive. Of these 4916 cases, whole-genome sequencing was successfully performed for 4168 (84·8%) isolates. 1219 (29·2%) of 4168 individuals were female and 2947 (70·7%) were male; the median age was 69·7 years (IQR 57·4-80·7). The dominant lineages were lineage 1 (1749 [42·0%] of 4168 isolates), lineage 2 (1510 [36·2%]), and lineage 4 (905 [21·7%]). 1069 (25·6%) of 4168 were genomically linked and formed 287 clusters. Lineage 2 isolates had higher odds (aOR 2·15 [95% CI 1·80-2·52]) than lineage 1 isolates of genomic clustering across all regions, whereas lineage 4 isolates had a significantly higher risk (2·75 [1·16-6·89]) of genomic clustering than lineage 1 only in the rural northeast region, inhabited primarily by indigenous populations. Spatial clustering analysis corroborated these lineage-region interactions. Although younger adults (<35 years) had the highest individual-level odds (5·64 [4·16-7·68]) of clustering in the logistic regression analysis compared with those aged 80 years or older, the transmission inference indicated that individuals aged 55-74 years were responsible for a greater proportion of inferred transmission events, contributing 50·8% of all transmission events. INTERPRETATION:This sequencing study revealed that older adults (aged ≥65 years) might have played a substantial and under-recognised role in the transmission of tuberculosis in Taiwan. The lineage-specific clustering and spatial patterns suggested that both pathogen characteristics and host demographics shaped tuberculosis transmission dynamics. These findings support the use of integrated genomic surveillance to guide precision tuberculosis control and motivate further research on age-specific transmission pathways and targeted interventions to advance tuberculosis elimination efforts. FUNDING:Taiwan National Health Research Institutes and Taiwan National Science and Technology Council.

Klebsiella pneumoniae invasive syndrome (KPIS), often arising from pyogenic liver abscesses, is characterized by metastatic infections and thrombotic complications. Diabetes mellitus (DM) is the most important risk factor for KPIS, as hyperglycemia promotes resistance of hypervirulent K. pneumoniae ;(hvKp) strains to phagocytosis and impairs neutrophil function. Given the interplay between platelet activation, inflammation, and thrombosis, aspirin, a well-established antiplatelet agent, has been associated with reduced incidence and recurrence of pyogenic liver abscesses in cohort studies. Platelets interact with neutrophils to form platelet - neutrophil aggregates (PNAs), which may contribute to KPIS pathogenesis. This study examined platelet - neutrophil interactions under hyperglycemic conditions using in vitro assays and in vivo models of diabetic mice infected with hvKp. High glucose concentrations significantly increased platelet activation, PNA formation, and bacterial survival. Salicylic acid, the bioactive metabolite of aspirin, reduced platelet activation and bacterial burden but did not impede PNA formation. Aspirin pre-treatment improved survival, reduced organ abscesses, and preserved tissue integrity in diabetic mice infected with hvKp. These results highlight the relationship between hyperglycemia, platelet activation, and immune dysregulation in KPIS, and support aspirin as a potential adjunctive therapy to mitigate thromboinflammatory complications of hvKp infection.

OBJECTIVE:Fluconazole non-susceptibility (FNS) in Candida tropicalis is an escalating global concern. We aimed to evaluate the clinical and molecular factors associated with 30-d mortality among patients with C. tropicalis invasive candidiasis (IC). METHODS:We performed a retrospective cohort study involving C. tropicalis IC episodes at a medical center in southern Taiwan (2018-2023). Multivariable logistic regression identified independent correlates of 30-d mortality. Furthermore, a subset of FNS isolates underwent MIC profiling, ERG11/UPC2 sequencing, qRT-PCR of target and efflux-pump genes, and phylogenetic analysis to investigate molecular mechanisms. RESULTS:We identified 341 C. tropicalis IC patients, with 30-d mortality rate of 45.8%. The average FNS rate was 8.2%, and the annual proportion among sterile-site isolates (ranging from 3.8% to 12.5%) exhibited no significant temporal trend. Independent factors associated with higher mortality included older age (AOR: 1.01 per year), fungemia (AOR: 2.50), recent chemotherapy (AOR: 1.62), and recent exposure to carbapenems (AOR: 1.40), daptomycin (AOR: 2.60), and polymyxins (AOR: 2.49). Dialysis was associated with lower mortality (AOR: 0.48). Importantly, neither FNS nor empiric echinocandin therapy was independently associated with 30-d mortality. Molecularly, FNS isolates were characterized by ERG11 Y132F ± S154F, a recurrent UPC2 Q289L substitution, up-regulation of efflux pump genes (CDR1, CDR2, and MDR1), and predominance of DST538/DST544 lineages. CONCLUSIONS:The 30-d mortality in C. tropicalis IC was primarily driven by host factors and infection site rather than FNS status. In healthcare settings with a low FNS prevalence, these findings suggest that empiric fluconazole therapy remains a reasonable treatment option.

Background:Cephalosporin susceptibility in methicillin-susceptible Staphylococcus aureus (MSSA) is typically inferred from oxacillin or cefoxitin results; however, the reliability of this surrogate approach remains uncertain. This study aimed to evaluate MSSA susceptibility to first- through fifth-generation cephalosporins and assess the predictive value of oxacillin minimum inhibitory concentrations (MICs) for identifying non-susceptibility. Methods:A total of 514 MSSA bloodstream isolates were collected from two hospitals in Taiwan. MICs for oxacillin and various cephalosporins were determined using broth microdilution. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of oxacillin MICs. Multilocus sequence typing (MLST) was performed on isolates exhibiting ceftaroline resistance or the susceptible-dose dependent (SDD) phenotype to examine their genetic diversity. Results:Non-susceptibility rates ranged from 4.9% to 6.2% for cefazolin, cefuroxime, ceftriaxone, and cefepime. For ceftaroline, while resistance was uncommon (1.4%), a notable proportion of isolates (9.7%) exhibited the SDD phenotype. An oxacillin MIC ≥0.25 mg/L predicted non-susceptibility to first- through fourth-generation cephalosporins with high accuracy (area under the curve [AUC] 0.827-0.875; negative predictive value [NPV] ≥ 98.7%) but was less predictive for ceftaroline (AUC 0.614). Among 44 isolates with elevated ceftaroline MICs, MLST identified 36 distinct sequence types, including 25 novel ones, indicating substantial genetic diversity. Conclusions:Cephalosporin non-susceptibility can occur among MSSA isolates. Although elevated oxacillin MICs were associated with higher MICs for several cephalosporins, this relationship was less predictive for ceftaroline. These findings highlight microbiological variability in MSSA cephalosporin susceptibility and may inform situations where direct MIC testing provides additional clarity.

Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical public health threat due to its broad-spectrum antimicrobial resistance and capacity for horizontal gene transfer. Methods Three clinical CRKP isolates, each carrying one of the three major classes of carbapenemase as class A (blaKPC), class B (blaNDM), and class D (blaOXA) were selected. A CRISPR/Cas9-based system (pCasKP-pSGKP) was employed to target carbapenem resistance genes in these strains (KP21040 with blaOXA-181, KP4-78 with blaNDM-1, and KP5-4 with blaKPC-2). Results CRISPR/Cas9-mediated editing led to partial reduction or complete loss of resistance plasmids, as evidenced by S1 nuclease-pulsed-field gel electrophoresis. This plasmid elimination correlated with a marked restoration of susceptibility to ertapenem, showing a greater than 64-fold reduction in minimum inhibitory concentrations (MICs) across all strains. In KP21040, MICs for ertapenem and levofloxacin decreased to 0.006 μg/mL and 0.125 μg/mL, respectively. Whole-genome analysis revealed that blaOXA-181 was flanked by insertion sequence (IS)26 elements, which mediated homologous recombination upon CRISPR-induced double-strand breaks, resulting in excision of a ∼15 kb segment including blaOXA-181 and qnrS1. These findings suggest that ISs may enhance CRISPR efficacy by promoting recombination-driven deletion. Moreover, the complete removal of all three resistance plasmids was observed in the KP5-4 strain harboring blaKPC-2. Conclusion This study demonstrates that CRISPR/Cas9-based genome editing can eliminate plasmid-encoded carbapenemase genes in clinical CRKP isolates and, in specific genetic contexts, facilitate the concurrent removal of associated quinolone resistance determinants. These findings support CRISPR-based genome editing as a proof-of-concept strategy for addressing plasmid-mediated multidrug resistance in Gram-negative pathogens.

BACKGROUND:Fusarium species are emerging pathogens known to cause both superficial and disseminated human infections. Aerosolized Fusarium species in healthcare settings have been associated with nosocomial fusariosis, particularly in patients with severe immunosuppression. OBJECTIVES:To analyse the phylogenetic relationships of clinical and hospital environmental Fusarium isolates and assess their susceptibility to available antifungal agents. METHODS:Clinical Fusarium isolates were procured from four hospitals in Taiwan, with environmental air and water sampling collected at Kaohsiung Chang Gung Memorial Hospital (KCGMH). All clinical and hospital environmental Fusarium isolates were identified through gene sequencing of translation elongation factor 1-α and internal transcribed spacer regions of ribosomal DNA. Antifungal susceptibility testing followed the CLSI M38-A3 broth microdilution method. RESULTS:A total of 41 clinical and 4 hospital environmental Fusarium isolates were identified, belonging to five species complexes (SC): F. solani SC (FSSC) (62.8%), F. fujikuroi SC (FFSC) (14.0%), F. incarnatum-equiseti SC (11.6%), F. dimerum SC (7.0%), and F. oxysporum SC (4.7%). Phylogenetic analysis revealed that clinical Fusarium isolates from KCGMH were closely related to environmental Fusarium isolates from air samples at the same hospital. Amphotericin B exhibited high activity against most Fusarium species. With the exception of FFSC, other Fusarium SC demonstrated significantly elevated MIC values to itraconazole, voriconazole, posaconazole, and isavuconazole. CONCLUSIONS:FSSC was the most prevalent SC in Taiwan, exhibiting higher MIC values for azoles than FFSC isolates. The clinical Fusarium isolates were observed to form clusters with the corresponding environmental isolates. The potential of airborne nosocomial infections in the healthcare environment cannot be overlooked.

Neutralizing anti–interferon-γ (IFN-γ) autoantibodies (nAIGAs) impair IFN-γ–mediated immunity, predisposing patients with nAIGAs to infection by nontuberculous mycobacteria, Talaromyces marneffei , and other intracellular pathogens. Current clinical management relies on continuous antimicrobial therapy, with no treatment offering sustained benefits. Here, we developed human chimeric autoantibody receptor (CAAR) T cells targeting autoreactive B cells expressing nAIGA B cell receptors (BCRs) using an IFN-γ receptor–irresponsive IFN-γ variant as bait. By exploiting a mouse model of nAIGA BCR-expressing B cell leukemia, we found that IFN-γ CAAR T cells lack off-target toxicity, including IFN-γ receptor cross-reactive toxicity and Fc-redirected toxicity. IFN-γ CAAR T cells substantially reduced circulating AIGAs secreted from target cells in vivo. Further, IFN-γ CAAR T cells effectively eliminated autoreactive B cells in ex vivo cultures of peripheral blood mononuclear cells from patients with nAIGAs. Together, these results demonstrate that IFN-γ CAAR T cells may be a promising strategy to ameliorate nAIGA-associated infections by eliminating autoreactive B cells.

ABSTRACT This study aimed to evaluate the in vitro activity of isavuconazole and ravuconazole against clinical Trichosporon isolates. Additionally, we assessed the performance of the Sensititre YeastOne (SYO) assay compared to the reference Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BMD) method for antifungal susceptibility testing. A total of 267 Trichosporon clinical isolates were collected from multiple centers in Taiwan between 2008 and 2020. The MIC values for amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole obtained using the CLSI BMD were compared to those determined using SYO. Among the seven antifungal agents tested using the CLSI BMD method, T. asahii isolates ( n = 224) exhibited significantly higher MICs for fluconazole, voriconazole, isavuconazole, and ravuconazole compared to non- T . asahii isolates ( n = 43) ( p < 0.05). Across all isolates, voriconazole demonstrated the lowest geometric mean (GM) MIC (0.06 mg/L). For T. asahii , the MIC₅₀, MIC₉₀, and GM MICs for posaconazole, isavuconazole, and ravuconazole were within ±1 twofold dilution, while mode MICs showed slightly greater variation (MIC₅₀, MIC₉₀, mode, and GM MICs were 0.25, 0.5, 0.5, and 0.28 mg/L; 0.12, 0.5, 0.12, and 0.17 mg/L; and 0.25, 0.5, 0.25, and 0.21 mg/L, respectively). The consistency of the MIC measurements between the SYO and CLSI BMD methods was assessed for amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole. The highest agreement within ±1 twofold dilution for T. asahii isolates was observed for posaconazole (94.2%). The essential agreement within ±2 twofold dilutions between both methods for all drugs was >97%. In conclusion, isavuconazole and ravuconazole demonstrated favorable in vitro activity against clinical Trichosporon isolates, while the SYO assay showed good concordance with the CLSI BMD method. IMPORTANCE Invasive infections caused by Trichosporon species pose significant therapeutic challenges, primarily due to their intrinsic resistance to echinocandins and the limited availability of effective treatment options. This study provides essential data on the in vitro activity of newer azoles and comprehensively evaluates the performance and concordance of the Sensititre YeastOne (SYO) and CLSI broth microdilution (BMD) methods. The current study analyzed 267 Trichosporon clinical isolates collected from multicenter settings in Taiwan. Our results demonstrate that both isavuconazole and ravuconazole exhibit favorable in vitro activities against Trichosporon species. For T. asahii , the essential agreement between the SYO and CLSI BMD methods exceeded 97% for all tested antifungal agents, indicating that the SYO method exhibits good concordance for most Trichosporon species. Further investigations are warranted to validate these findings and to assess their clinical implications.

BACKGROUND:By June 2024, Taiwan reported 381 Mpox virus (MPXV) cases and one death. This study aims to analyze the characteristics and clinical presentations during the first outbreak of Mpox in Taiwan. METHODS:The study was conducted across 16 hospitals and included patients aged 20 and older diagnosed with Mpox between May 2022 and March 2024. Data on demographics, symptoms, medication, vaccination history, and laboratory results were collected. Patients with HIV (PWH) were classified based on their HIV plasma viral load (PVL): undetectable viral load (UDVL) was defined as PVL<50 copies/ml, while detectable viral load (DVL) was higher. Statistical analyses examined differences among HIV-negative individuals, PWH with UDVL, and PWH with DVL, with P < .05 considered significant. RESULTS:A total of 178 patients were analyzed; 99.4 % were male, with 94.9 % identifying as gay, bisexual, or men who have sex with men. Two-thirds were PWH, and among them, two-thirds had UDVL. PWH with UDVL showed a lower incidence of concurrent STIs compared to those with DVL (P < .05), with syphilis being the most common STI. The vaccination rate against MPXV was about 7 %, with only nine patients vaccinated prior to acquiring the infection. Symptoms often included fever, and infections predominantly affected the genitourinary system. The number of vesicles was significantly associated with PVL (P < .05), with UDVL patients exhibiting fewer vesicles and less confluent skin lesions than those with DVL. CONCLUSION:Most MPXV infections in Taiwan occur among PWH, particularly those with UDVL. Enhanced screening, vaccination efforts, and integrated STI testing are crucial in addressing this outbreak.

Background and Objectives: Spirituality and loneliness are widely recognized as important aspects of holistic healthcare. This observational study was conducted among hospitalized patients with chronic illnesses in a medical ward during three waves of the epidemic in Taiwan, from April 2022 to March 2023, to examine changes in spiritual needs and loneliness. Materials and Methods: These waves were classified as the first wave (outbreak period, April 2022 to July 2022); second wave (mitigation period, August 2022 to November 2022); and third wave (December 2022 to March 2023). The Spiritual Needs Scale and Loneliness Scale were used to assess changes in spiritual needs and loneliness of the enrolled patients across the different waves of the epidemic. Results: We found that the spiritual needs of the enrolled patients were higher during the outbreak period (F = 9.847, p < 0.001) compared to the other periods. In addition, loneliness was higher during the conclusion period (F = 45.764, p < 0.001) compared to the other two periods. Age (r = 0.261, p < 0.001) and the Charlson comorbidity index (r = 0.193, p < 0.01) were significantly positively correlated with spiritual needs. Furthermore, the number of daily confirmed COVID-19 cases (r = −0.392, p < 0.001) was significantly negatively correlated with loneliness. Conclusions: Hospitalized patients with chronic illnesses experienced heightened spiritual needs during the COVID-19 outbreak, while loneliness increased as the epidemic waned. The study’s prospective observational design is a strength, but incorporating additional temporal measures between periods would have enhanced the findings.

Timely pathogen identification in bloodstream infections is crucial for patient care. A comparison is made between positive blood culture (BC) pellets from serum separator tubes using a direct identification (DI) method and colonies on agar plates from a short-term incubation (STI) method with a matrix-assisted laser desorption/ionization Biotyper for the evaluation of 354 monomicrobial BCs. Both the DI and STI methods exhibited similar identification rates for different types of bacteria, except for Gram-positive and anaerobic bacteria. The DI method’s results aligned closely with the STI method’s results for Enterobacterales, glucose-non-fermenting Gram-negative bacilli (GNB), and carbapenem-resistant Enterobacterales. The DI method exhibited high concordance with the conventional method for GNB identification, achieving 88.2 and 87.5% accuracy at the genus and species levels, respectively. Compared with the STI method, the DI method showed a less successful performance for Gram-positive bacterial identification (50.5 vs. 71.3%; p < 0.01). The DI method was useful for anaerobic bacterial identification of slow-growing microorganisms without any need for colony growth, unlike in the STI method (46.7 vs. 13.3%; p = 0.04). However, both methods could not identify yeast in positive BCs. Overall, the DI method provided reliable results for GNB identification, offering many advantages over the STI method by significantly reducing the turnaround time and enabling quicker pathogen identification in positive BCs.

Background: In Taiwan, COVID-19 outbreaks caused by the Omicron variant occurred in 2022. We investigated the incidence of candidemia during COVID-19 pandemic and the mortality of candidemia patients with COVID-19 in Taiwan. Methods: The incidence of candidemia and fluconazole susceptibility of Candida species before (2015-2019) and during COVID-19 pandemic (2020-2023) at Kaohsiung Chang Gung Memorial Hospital were investigated. The associated factors with mortality in candidemia patients during COVID-19 pandemic were analyzed. Candidemia patients who had COVID-19 within the prior 90 days (case group, n = 34) were propensity-score matched for age, ICU admission, and abdominal surgery in a 1:4 ratio with candidemia patients without COVID-19 (control group, n = 136). Results: Age (adjusted odds ratio [AOR] = 1.02, 95% CI: 1.01-1.03), ICU stay (AOR = 1.84, 95% CI: 1.29-2.62), higher Charlson comorbidity index (AOR = 1.08, 95% CI: 1.03-1.13), corticosteroid use (AOR = 1.50, 95% CI: 1.04-2.17) were associated with increased risk of mortality; abdominal surgery (AOR = 0.47, 95% CI: 0.29-0.74) and infected by Candida parapsilosis (AOR = 0.61, 95% CI: 0.38-0.98) were associated with decreased risk of mortality. After matching, there was no significant difference in mortality rates between the case and control groups. The incidence of candidemia increased from 196 to 278 patients/100,000 admissions during COVID-19 pandemic, while the causative species of candidemia and fluconazole susceptibility rates were similar. Conclusion: While the incidence of candidemia increased during COVID-19 pandemic, there was no significant difference in mortality between candidemia patients with and without COVID-19 in the Omicron era. Copyright (c) 2024, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).

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 <50 copies/mL (87.5% vs 87.7%) and composite unfavorable outcome (7.7% vs 7.7%). PWH aged >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/Purpose: Nocardiosis is an uncommon infectious disease. This study aimed to assess the clinical outcome of patients with nocardiosis and examine the antimicro-bial susceptibility profiles of Nocardia spp. isolated.Methods: We retrospectively reviewed the medical records of all inpatients diagnosed with no-cardiosis between 2011 and 2021. The identification of Nocardia spp. at the species level was performed with the use of MALDI-TOF and 16S rRNA assays. The antimicrobial susceptibility of Nocardia spp. was performed using the microbroth dilution method. Factors associated with 90-day all-cause mortality were identified in multivariate logistic regression analysis.Results: Of 60 patients with nocardiosis in the 11-year study period, the lungs (55.0%) were the most common site of involvement, followed by the skin and soft tissue (45.0%). Twenty-two pa-tients (36.7%) died within 90 days following the diagnosis. All of the Nocardia isolates were sus-ceptible to trimethoprim-sulfamethoxazole, linezolid, and amikacin, whereas more than 70% of the isolates were not susceptible to ciprofloxacin, imipenem-cilastatin, moxifloxacin, cefepime, and clarithromycin. Nocardiosis involving the lungs (relative risk [RR], 9.99; 95% confidence interval [CI], 1.52-65.50; p = 0.02), nocardiosis involving the skin and soft tissue (RR, 0.15; 95% CI, 0.02-0.92; p = 0.04), and treatment with trimethoprim-sulfamethoxazole (RR, 0.14; 95% CI, 0.03-0.67; p = 0.01) were independently associated with 90-day all-cause mortality.Conclusions: Nocardia spp. identified between 2011 and 2021 remained fully susceptible to trimethoprim-sulfamethoxazole, linezolid, and amikacin. Nocardiosis of the lungs, skin and soft tissue infection, and treatment with trimethoprim-sulfamethoxazole were independently asso-ciated with 90-day all-cause mortality.Copyright (c) 2022, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction High-dose dual therapy (HDDT) can attain acceptable eradication rates provided that the optimal doses, timing and treatment duration are applied. The existing evidence still shows inconsistent reports (< 90%) on HDDT therapy except in some Asian countries. We aimed to assess and compare the efficacy of 14-day HDDT by comparing it to 14-day rabeprazole-containing hybrid therapy (HT) and to investigate the host and bacterial factors predicting the treatment outcomes of eradication therapies. Methods In this open-label, randomized controlled trial, we recruited 243 naïve Helicobacter pylori -infected patients from September 1, 2018, to November 30, 2021. They were randomly allocated (1:1) to the HDDT group (rabeprazole 20 mg and amoxicillin 750 mg q.i.d for 14 days, n = 122) and the HT group (rabeprazole 20 mg and amoxicillin 1 g b.i.d. for 7 days, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg b.i.d. for 7 days, n = 121). Twelve patients were absent during follow-up in the HDDT group and 4 in the HT group, resulting in 110 for the HDDT group and 117 for HT group in the per protocol (PP) study. The outcome was determined by urea breath tests 8 weeks later. Results The eradication rates for the HDDT and HT groups were 77.0% (95% confidence interval [CI]: 68.5% to 84.1%) and 94.2% (95% CI: 88.4% to 97.6%) ( P < 0.001) in intention-to-treat analysis; 85.5% (95% CI: 77.5% to 91.5%) and 97.4% [95% CI: 92.6% to 99.5%] ( P = 0.001) in per protocol analysis. The adverse event rates were 7.3% in the HDDT group and 14.5% in the HT group ( P = 0.081). The habit of coffee drinking was the dependent factor for eradication failure in the HDDT group (88.2% vs. 68.8%, P = 0.040), but had no influence in the HT group (97.9% versus 95.0%, P = 0.449) in the univariate analysis. Conclusion This study demonstrated that 14-day rabeprazole-containing HDDT did not achieve > 90% eradication rates for first-line H. pylori eradication as 14-day rabeprazole-containing HT did. HDDT is a potentially beneficial combination, which involves only two drugs with mild adverse effects; more precise studies are urged to find answers regarding these failures. This clinical trial was registered retrospectively on 28 November, 2021, as ClinicalTrials.gov identifier: NCT05152004.

Swallowing difficulties often occur in older adult patients during acute hospitalization, leading to reduced nutritional intake, increased frailty, and various psychosocial challenges. This randomized controlled study aimed to assess the effects of two interventions, thickeners and swallowing exercises, on the spiritual well-being, physical activity, and happiness of older adult patients with swallowing difficulties during acute hospitalization from October 2019 to August 2020. Sample size calculation was performed using a conservative estimate approach, resulting in an estimate-required sample size of 42 participants. The sampling method was a random cluster sampling approach, with three ward rooms assigned to the thickeners group, swallowing exercises group and control group, respectively. Seventy-two participants were assigned to the intervention groups (thickeners or swallowing exercises) or the control group using a 1:1:1 stratified random assignment. Data were collected before and after the intervention, and matched samples were analyzed using t-tests, ANOVA, and generalized estimating equations for statistical analysis. Both intervention groups showed significant improvements in spiritual well-being (p < 0.001), physical activity (p < 0.001), and happiness (p < 0.001) compared to the control group. However, there were no significant differences between the intervention groups. Our findings suggest that interventions involving thickeners and swallowing exercises have positive effects on the spiritual well-being, physical activity, and happiness of older adult patients with swallowing difficulties during acute hospitalization and emphasize the importance of implementing these interventions to enhance the overall well-being and quality of life of this vulnerable patient population.