Background In addition to the main goal of T cell engraftment, the functional reconstitution of B cell function is an important indicator of successful hematopoietic stem cell transplantation (HSCT) for severe combined immunodeficiency (SCID) patients. Objective Poor functional reconstitution of B cell function may relate to lower degree of Major Histocompatibility Complex (MHC) compatibility in children with SCID after HSCT. Study Design We aimed to analyze the outcomes of HSCT in children with SCID in a referral tertiary center in southern Taiwan. We collected data retrospectively from all seven infants with SCID who received HSCT and were followed-up at the center during 2005-2025. Results All patients survived with reconstituted T cells during the follow-up period. One hundred percent T cell engraftment of donor cells are noted in all patients while variable degrees of chimerism were noted in other leukocytes. However, the extent of B cell chimerism does not appear to determine the outcome of B cell functional recovery. Two haploidentical-transplant patients required regular immunoglobulin supplement to prevent frequent infections. Conclusion Newborn screening for SCID may successfully identified patients with SCID and early HSCT helped them to survive the previously fatal disease. However, poor immunoglobulin recovery requiring lifelong immunoglobulin replacement was observed in the two patients who underwent haploidentical HSCT. Haploidentical transplantation as a potential cause of compromised B cell recovery in SCID treatment should be further investigated.
AIMS:To evaluate the association between fluoroquinolone (FQ) use and incident aortic aneurysm (AA), aortic dissection (AD), aneurysm-related surgery, and all-cause mortality in a large U.S. multicenter database and to explore the influence of comparator selection and infection-related confounding. METHODS AND RESULTS:A retrospective cohort of 180,936 patients prescribed FQs was compared with 180,936 propensity score-matched patients who received comparator antibiotics. Matching was conducted 1:1 based on demographics, socioeconomic status, lifestyle factors, comorbidities, and medication use. The primary outcome was the 90-day incidence of AA/AD, evaluated using adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). The FQ cohort was not found with an elevated risk of AA (aHR:0.95; 95%CI:0.83-1.08) but with elevated risk of AD (aHR:1.38; 95%CI:1.01-1.89), aneurysm-related surgery (aHR:2.32; 95%CI:1.75-3.08) and mortality (aHR:2.75, 95%CI:2.62-2.89). Exploratory sensitivity analyses using alternative comparator groups yielded substantially different estimates, including lower observed risks of AA/AD when last-line antibiotics were used as comparators (AA: aHR, 0.53 [95%CI:0.47-0.60]; AD: aHR, 0.31 [95%CI:0.23-0.43]). These findings suggest important residual confounding related to comparator selection, infection indication, and infection severity. CONCLUSION:In the primary analysis, FQ use was not associated with overall AA but was associated with increased risks of AD, aneurysm-related surgery, and mortality. Estimates varied substantially across comparator-based sensitivity analyses, suggesting potential residual confounding by indication and infection severity. These findings should not be interpreted as establishing the absence of AA/AD risk associated with FQ use.
PURPOSE:The clinical significance of positive acid-fast bacilli (AFB) by microscopy smear in respiratory specimens remains poorly understood in patients with a history of successfully treated pulmonary tuberculosis (PTB). METHODS:A retrospective study was conducted to screen patients with PTB between 2009 and 2020. They were enrolled if microscopic smears of AFB were positive after they completed successful treatments. The first date of a positive AFB smear after treatment completion was denoted as the index date. According to whether culture results indicated Mycobacterium tuberculosis (Mtb), subjects were categorized into Mtb and non-Mtb groups. RESULTS:A total of 84 patients were included, with 27 (32.1%) patients in the Mtb group. The Mtb group had a higher proportion of active smokers and strong positive smears of AFB than the non-Mtb group. Radiologically, the rate of cavitation on the index date was significantly higher in the Mtb group than in the non-Mtb group (77.8 vs. 22.8%, p < 0.001, respectively). By multivariable logistic regression analysis, cavitation on the index date [adjusted odds ratio (aOR): 6.80, p = 0.003] and active smoker (aOR: 7.14, p = 0.044, vs. non-smoker) were independent risk factors of the Mtb group. There were 52 patients (61.9%) having polymerase chain reaction (PCR) tests. While the sensitivity of PCR was 94.1%, the specificity was only 60.0%. CONCLUSIONS:The detection of AFB by microscopic smears and positive PCR might not be sufficient for diagnosing recurrent PTB. Integrating the clinical factors, including active smoking and cavitation, might enhance the diagnostic power.
BACKGROUND:Acute undifferentiated febrile illness (AUF) remains a challenge in medical diagnosis. This study aimed to investigate the microbial profiles of non-leptospirosis AUF patients from Sisaket province, an endemic region for leptospirosis, and to elucidate their associations with clinical parameters. METHODS:Blood samples from 78 non-leptospirosis AUF patients were confirmed negative for leptospirosis by bacterial culture, lipL32-qPCR, and the microscopic agglutination test. 16S rDNA and ITS sequencing were used to identify bacterial and fungal communities. Patients were categorized into Only Bacteria (OB), Only Fungi (OF), and Both Bacteria and Fungi (BBF) groups. Microbial differences were assessed using Principal Coordinate Analysis (PCoA) and associations with clinical variables analyzed using Generalized Linear Models (GLM). RESULTS:Stenotrophomonas emerged as the predominant bacterial genus in both OB and BBF groups, while Aspergillus and Candida dominated the fungal profiles in OF and BBF groups. Bacterial compositions differed significantly between OB and BBF groups (P = 0.002), indicating that concurrent bacterial-fungal presence alters bacterial community structure, whereas fungal profiles remained stable. GLM analysis revealed significant associations between specific microbial taxa and clinical parameters, including blood pressure, temperature, hematological indices, and liver function tests. CONCLUSION:Our study sheds light on the microbial landscape in non-leptospirosis AUF patients, establishing connections with clinical parameters. This holistic approach enriches our understanding of AUF's etiology, presenting avenues for targeted diagnostic and therapeutic strategies in systemic infections.
In this study, we report the first proteomic characterization of extracellular vesicles (EVs) in a Mucorales species. EV cargo of Mucor lusitanicus contains multiple virulence-associated and biomarker-relevant proteins, supporting a potential role for EVs in host-pathogen interaction and providing a basis for future diagnostic and functional studies.
This systematic review and meta-analysis evaluated therapeutic strategies for iliopsoas muscle abscess (IPA). Overall treatment success and mortality rates were 80.4% and 8.3%, respectively, with mortality escalating in complex cases. Modality-specific descriptive estimates showed mortality rates of 4.2% for percutaneous catheter drainage (PCD), 6.2% for open surgical drainage (OSD), and 12.7% for antibiotic monotherapy, with corresponding treatment success rates of 71.4%, 92.0%, and 64.6%, respectively. Length of hospital stay and recurrence were summarized descriptively because of inconsistent definitions and reporting across studies. Staphylococcus species were the most frequently identified pathogens among evaluable pus cultures (38.1%), with S. aureus predominating in primary IPA. In contrast, IPA of gastrointestinal or genitourinary origin was more frequently associated with Enterobacteriaceae. These findings support prompt risk stratification and individualized management based on abscess etiology, morphology, and local microbiology.
INTRODUCTION:Community-acquired pneumonia constitutes a significant burden to healthcare systems. While international guidelines recommend beta-lactam plus macrolide in treating severe community-acquired pneumonia, doxycycline instead of macrolide provides antimicrobial activity to macrolide-resistant organisms that are highly prevalent in East Asia and avoids its side effects. Yet, doxycycline's immunomodulatory effect is not as well studied. We investigated the comparative efficacy of doxycycline with azithromycin in the treatment of severe community-acquired pneumonia. METHODS:From 1 January 2014 to 31 December 2023, consecutive adult patients with pneumonia or pulmonary sepsis requiring intensive care within 48 h of hospital admission, who received a beta-lactam in combination with either azithromycin or doxycycline were retrospectively reviewed. The two groups were matched by propensity scores and compared for all-cause mortality at day 30. RESULTS:A total of 670 patients were analysed. Streptococcus pneumoniae was the dominant bacteria identified in one fourth of all patients with a bacterial cause. 75% of those cultured were macrolide resistant. Mycoplasma pneumoniae was detected in 0.9% of all patients, while detection of Legionella pneumoniae was 2.8 times higher. Propensity score matching resulted in 250 pairs of patients with balanced covariates. Thirty-day mortality did not differ between groups (21.1% in beta-lactam/azithromycin vs 19.2% in beta-lactam/doxycycline, p = 0.649). A longer duration of azithromycin more than or equal to 3 days did not alter this outcome. CONCLUSIONS:Beta-lactam/azithromycin or beta-lactam/doxycycline are viable empirical treatments for severe community-acquired pneumonia despite local resistance patterns. Our result did not support a longer duration of azithromycin over doxycycline.
BACKGROUND:Omicron is known for its higher transmissibility and milder respiratory symptoms than those of other SARS-CoV-2 variants. How comorbidities contribute to mortality outcomes in Omicron-related COVID-19 remains unclear. This study compared clinical features and outcomes between Omicron and non-Omicron variants and identified risk factors for in-hospital mortality. METHODS:This retrospective cohort study was conducted from April 2020 to September 2022. Patients with COVID-19 infection were divided into Omicron and non-Omicron groups. Demographic data, laboratory results, and treatment information were collected and analyzed. Clinical outcomes for different variants were analyzed. RESULTS:The Omicron group had a greater burden of comorbidities but exhibited lower COVID-19 disease severity and fewer complications than did the non-Omicron group. Overall mortality was relatively high in the Omicron group, primarily due to non-COVID-related causes. In multivariate analysis, a Charlson comorbidity index score of ≥3 (odds ratio [OR] = 4.60, 95% confidence interval [CI] = 1.94-10.91, p < 0.001), severe or critical COVID-19 (OR = 1.60, 95% CI = 1.24-2.07, p < 0.001), a high white blood cell count (OR = 1.00, 95% CI = 1.00-1.00, p = 0.021), and a high C-reactive protein level (OR = 1.01, 95% CI = 1.00-1.01, p = 0.003) emerged as positive predictors of COVID-19-related mortality. CONCLUSION:Severe or critical COVID-19 and a Charlson comorbidity index score of ≥3 were independently associated with high in-hospital mortality. Intensive monitoring and early intervention should be prioritized for high-risk groups to improve clinical outcomes.
BACKGROUND:Nocardia species are emerging pathogens of increasing significance, particularly in immunocompromised hosts. Due to diverse clinical manifestations and resistance patterns, accurate identification is critical. This study characterized species distribution in Taiwan, evaluated identification methodologies, and identified mortality risk factors. METHODS:We analyzed 99 Nocardia isolates from 76 patients at a Taiwanese tertiary center (2011-2025). Identification via MALDI-TOF MS and concatenated gene sequencing (16S rRNA, secA1, hsp65) was compared against whole-genome sequencing (WGS). Susceptibility was tested using broth microdilution. Potential mortality-associated variables were first evaluated in univariate analyses, and the final multivariable model was constructed using Firth's penalized logistic regression. RESULTS:N. brasiliensis was most prevalent (27/76; 35.5%), primarily causing cutaneous infections, while N. farcinica (25/76; 32.9%) was linked to pulmonary cases and higher mortality. Firth's penalized logistic regression identified immunosuppressant use (OR 18.44; 95% CI, 3.62-93.89) and higher Charlson Comorbidity Index (CCI) (OR 1.70; 95% CI, 1.23-2.35) as independent predictors of mortality. High rates of imipenem non-susceptibility were observed in N. farcinica (85.7%) and N. cyriacigeorgica (83.3%). In addition, the proportion of imipenem non-susceptible isolates increased significantly during 2020-2025 compared with 2011-2019 (94.1% vs. 67.1%, p = 0.024). Regarding species identification, MALDI-TOF MS demonstrated acceptable performance (PPA = 0.89), whereas concatenated gene sequencing achieved perfect agreement with WGS (PPA = 1.00). CONCLUSIONS:Accurate species-level identification is crucial for guiding antimicrobial therapy, especially given the emerging burden of imipenem non-susceptibility in clinically important Nocardia species. Immunosuppressant use and a higher CCI were independently associated with mortality, highlighting the importance of early recognition and appropriate management in high-risk patients. Concatenated multilocus sequence analysis based on 16S rRNA, secA1, and hsp65 provides a practical and accurate alternative to WGS for routine species identification in clinical microbiology laboratories.
BACKGROUND:Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major cause of healthcare-associated infections, especially in intensive care units. Its rapid acquisition of antimicrobial resistance necessitates molecular epidemiology to inform infection control measures and treatment strategies. This study evaluated antimicrobial resistance phenotypes and the prevalence of resistance genes among clinical CRAB isolates in Thailand, complemented by MLST-based population structure analysis incorporating a temporal dimension of clonal distribution compared with previous reports. METHODS:This study analyzed 316 clinical A. baumannii isolates from five regions across Thailand (2022-2023). Species confirmation was performed by PCR targeting blaOXA-51-like. Antimicrobial susceptibility testing against thirteen antibiotics followed CLSI 2024 guidelines. Resistance genes were identified by PCR, and MLST with PHYLOViZ goeBURST characterized population structure. RESULTS:All isolates demonstrated carbapenem resistance, with the majority exhibiting extensively drug-resistant (XDR) phenotypes. Isolates showed resistance to β-lactams, fluoroquinolones, aminoglycosides, tetracyclines, and sulfamethoxazole/trimethoprim, while remaining susceptible to minocycline. MLST revealed ST2 as the predominant clone (78.8%), followed by ST164 (8.9%) and ST16 (6.0%). Class A β-lactamase blaVEB was highly detected (95.3%), followed by Class D β-lactamase blaOXA-23-like (93.7%). Temporal distribution of clonal lineages revealed persistence of major STs without clonal shifts, with ST2, ST164, and ST25 remaining dominant across sampling periods. ST164 (IC11) notably exhibited high resistance gene carriage capacity. CONCLUSIONS:The results reinforce the predominance and persistence of ST2 (IC2) in the CRAB population circulating in Thailand and geographic dissemination of high-risk clones across different regions. This highlights the importance of continuous molecular surveillance to guide infection prevention and antimicrobial stewardship.
BACKGROUND:Vibrio vulnificus is a highly virulent pathogen associated with rapidly progressive sepsis and necrotising soft-tissue infection, particularly among patients with diabetes or chronic liver disease. Effective treatment options remain limited, especially in the setting of high bacterial burden or immunocompromis. METHODS:We performed an integrated preclinical assessment of mitomycin C (MMC) alone and in combination with ciprofloxacin (CIP) using in vitro susceptibility testing and a neutropenic murine model challenged with increasing inocula of V. vulnificus. Myelotoxicity, organ-specific toxicity, and the development of resistance under subinhibitory MMC exposure were evaluated through haematological profiling and histopathology. RESULTS:MMC demonstrated potent in vitro activity and conferred complete protection in mice challenged with low bacterial inocula (103-104 colony-forming units (CFU)/mL). Although efficacy declined with increasing bacterial burden, combination therapy with MMC and ciprofloxacin significantly improved survival across all inoculum levels, achieving complete protection at concentrations up to 1.4 ⨯ 107 CFU/mL and partial protection at 4.3 ⨯ 107 CFU/mL. The combination regimen was not associated with dose-dependent myelosuppression, and no hepatotoxicity or nephrotoxicity was observed. Exposure to subinhibitory concentrations of MMC did not result in increased minimum inhibitory concentrations over time. CONCLUSIONS:MMC-CIP combination therapy demonstrated synergistic efficacy against severe V. vulnificus infection in a neutropenic mouse model and may represent a promising therapeutic option. Dose-limiting myelotoxicity and the potential for resistance necessitate cautious dosing and further clinical investigation. This study addresses a critical therapeutic gap in severe V. vulnificus infection by proposing a mechanistically rational, dose-optimized adjunctive strategy supported by robust preclinical evidence.
BACKGROUND:Unusual cell death in immune cells contributes to immunosuppression in sepsis. Neutrophils play a crucial role in fighting pathogens. However, the roles of apoptosis, pyroptosis, and neutrophil extracellular trap (NET) formation (NETosis) in neutrophils during sepsis remain unclear. METHODS:Patients admitted to the intensive care unit with sepsis were enrolled between August 2021 and July 2024. Apoptosis, pyroptosis, and NETosis in circulating neutrophils were measured on days 1 and 8. Finally, data from 43 patients were used for analysis. RESULTS:On day 8, the count and percentage of neutrophils dying primarily through apoptosis were significantly higher in non-survivors compared to survivors (9.7 vs. 2.0/μL; 7.2 vs. 3.4%, respectively). General Linear Model revealed significant differences in both the percentage (p = 0.035) and count (p = 0.008) of apoptosis-predominant neutrophil death on days 1 and 8 between survivors and non-survivors. The percentage and count of apoptosis-predominant neutrophils on day 8 were positively correlated with the APACHE II score on day 8 with correlation coefficients of 0.560 (p < 0.001) and 0.513 (p = 0.002), respectively. SOFA score was weakly positively correlated with the count of apoptosis-predominant neutrophils on days 1 and 8 with correlation coefficients of 0.347 (p = 0.023) and 0.375 (p = 0.029), respectively. CONCLUSION:This study suggests that increased neutrophil death via apoptosis is associated with higher mortality rates in sepsis patients. Neutrophil apoptosis levels correlated with disease severity scores. Larger-scale studies are needed to confirm these findings.
A close but genetically divergent retrovirus named HIV-2 was discovered in 1986 in West African patients with AIDS negative or indeterminate for HIV-1 antibodies. Viral replication is lower in HIV-2, being plasma viremia often undetectable or low. As result, HIV-2 transmission either by sex or vertically, is lower compared to HIV-1. Alongside, CD4+ T-cell declines occur slowly and clinical manifestations of immunodeficiency may appear after 15 years in HIV-2 patients. Over 10% of HIV-2 carriers may remain asymptomatic lifelong. The susceptibility of HIV-2 to antiretroviral drugs is generally lower than for HIV-1, being non-nucleoside reverse transcriptase inhibitors non active. Some protease inhibitors, as darunavir, are effective. All integrase inhibitors block HIV-2, and either dolutegravir or bictegravir are the preferred drug choices. Specific viral load tests must be used to monitor HIV-2 plasma viremia. Trends in epidemiological surveys confirm that the HIV-2 pandemic is falling down with less infected persons yearly in endemic regions and globally.
INTRODUCTION:Chryseobacterium indologenes bacteremia poses significant therapeutic challenges due to intrinsic multidrug resistance and the absence of established Clinical and Laboratory Standards Institute breakpoints for fluoroquinolones. We aimed to develop machine learning models to predict mortality and guide fluoroquinolone treatment decisions. METHODS:In this retrospective study of 61 patients, we compared Logistic Regression, Conservative Random Forest, and two Calibrated Random Forest variants (Sigmoid/Isotonic) using Borderline Synthetic Minority Over-sampling Technique and conservative parameter settings to address small-sample limitations. RESULTS:Mortality was 21.3%, with shock identified as the strongest predictor (p < 0.001). Conservative Random Forest achieved the highest area under the curve (0.908) and good calibration stability. Notably, complex calibration methods yielded unstable probability curves, revealing a "calibration paradox" in small-sample settings. A risk stratification system based on optimal models successfully identified low-risk patients suitable for fluoroquinolone therapy. CONCLUSIONS:For rare infections with limited data, robust, conservative RF demonstrated a trend of stable calibration characteristics. This study provides an objective clinical decision support tool for Chryseobacterium indologenes treatment when standard susceptibility interpretation is unavailable.
BACKGROUND:Here, we aim to determine the effect of previous infection with Paracoccidioides brasiliensis (Pb18), a primary human pathogenic fungus, associated with high mortality and morbidity rates, on the outcome of SARS-CoV-2 infection. METHODS:The K18hACE2 transgenic mice were infected with 1 × 106 yeasts of the Pb18 fungus followed by the infection with 5 × 104 Plaque-Forming Unit (PFU) of the SARS-CoV-2 virus. RESULTS:The coinfected mice exhibit lower weight loss and mortality compared to mice infected with the virus alone. Moreover, the inflammatory infiltrate and the viral load of lung, heart, spleen, and brain were lower, suggesting that prior infection with the Pb18 leads to increased resistance against the virus infection. In addition, after SARS-CoV-2 infection, a lower frequency of inflammatory monocytes in the lung tissue of mice previously infected with Pb18 was found. We also observed that mice infected only with SARS-CoV-2 had higher expression of pro-inflammatory cytokines and lower frequency of dendritic cells, alveolar and interstitial macrophages and T lymphocytes in lung tissue compared to mice coinfected or infected only with the fungus. The fungus-induced resistance is dependent on the IFN-I signaling pathway, since treatment with antibody against IFNAR impaired animal survival and viral load. CONCLUSION:This study reveals a distinct outcome compared to what is typically observed in opportunistic fungal coinfections, highlighting the pathways necessary to induce resistance against viral infections.
BACKGROUND:The occurrence of foreign body (FB) infections in patients with Staphylococcus aureus bacteraemia (SAB) can lead to serious complications. We therefore sought to evaluate the host risk factors and bacterial determinants associated with FB infection following SAB. METHODS:We retrospectively included patients hospitalized with a SAB and carrying FB, over a four-year period. Factors associated with FB infection were assessed with multivariable logistic regression analysis. Bacterial determinants (lineage and virulence factors) were determined using whole genome sequencing. RESULTS:We included 104 patients of whom 40 patients (38.5%) with FB infection. Factors associated with FB infection were community-acquired SAB (OR = 3.8; 95% confidence interval, CI [1.36-10.59]; p = 0.011), Charlson's score >3 (OR = 0.39; 95% CI [0.16.-0.99]; p = 0.048 and unknown source of infection (OR = 3.54; 95% CI [1.34-9.33]; p = 0.011). No clonal complex or virulence gene was associated with a risk of FB infection in patients with SAB. CONCLUSION:FB infection is frequent in patients with SAB, particularly when the bacteremia is community-acquired. Our results suggest that bacterial characteristics (clonal complex or virulence factors) are not involved in the occurrence of FB infection in patients with SAB.
BACKGROUND:Sepsis diagnosis remains challenging, and conventional biomarkers such as CRP and PCT show limited specificity. Circulating microRNAs (miRNAs) have been investigated as diagnostic biomarkers, but substantial methodological variability across studies has limited the interpretation of current evidence. Previous meta-analyses largely evaluated miRNAs as a single biomarker category, leaving variation across biologically distinct subgroups insufficiently explored. METHODS:Following PRISMA 2020 and PRISMA-DTA 2018 guidelines, we systematically searched PubMed, EMBASE, and Scopus through April 2026. Study quality was assessed using QUADAS-2, and pooled diagnostic performance was analyzed using a hierarchical summary receiver operating characteristic (HSROC) model. Subgroup analyses explored clinical, methodological, and functional sources of heterogeneity. RESULTS:Thirty-nine studies involving 59 distinct miRNAs were included. Pooled sensitivity was 0.79 (95% CI: 0.76-0.82) and specificity was 0.82 (95% CI: 0.78-0.85), with an AUROC of 0.87 (95% CI: 0.84-0.90). Substantial heterogeneity was observed (sensitivity I2 = 92.4%; specificity I2 = 89.0%). In exploratory functional subgroup analyses, IL-1β-associated miRNAs demonstrated higher overall diagnostic accuracy (AUROC 0.90, 95% CI: 0.87-0.92), while endothelial dysfunction-related miRNAs showed comparatively higher specificity. CONCLUSION:Circulating miRNAs demonstrate moderate diagnostic accuracy for sepsis, with functional subgroup analyses showing differences across biologically distinct miRNA categories. Diagnostic performance appears to vary according to both biological function and methodological context. Substantial heterogeneity limits the generalizability of current evidence. Future multicenter studies using standardized protocols and infected non-septic control groups are needed to determine the clinical utility of pathway-specific miRNA panels.
