Infection and Drug Resistance最新文献

Background: Anti-interferon-γ autoantibodies (AIGAs) immunodeficiency syndrome is a rare acquired disorder characterized by impaired IFN-γ signaling, predisposing patients to severe intracellular infections. While disseminated non-tuberculous mycobacteria (NTM) and Talaromyces marneffei (TM) are well-documented pathogens, the clinical and immunological features of Salmonella coinfection remain poorly characterized.

Methods: This retrospective study analyzed 12 HIV-negative patients with AIGAs-positive status and confirmed Salmonella infection at the First Affiliated Hospital of Guangxi Medical University, China (2021-2024). Data included demographics, clinical manifestations, laboratory findings, co-infections, treatment, and outcomes. AIGAs were detected via ELISA and Western blot, with neutralizing activity confirmed by STAT1 phosphorylation inhibition.

Results: The cohort was predominantly composed of middle-aged males (83.3%, mean age 55.75 ±8.06 years). The most common symptoms were fever, fatigue and cough (each 91.7%), followed by poor appetite (83.3%), systemic symptoms (chills, weight loss; 58.3%) and dyspnea (58.3%). Bone or joint pain occurred in 41.7% and gastrointestinal complaints (abdominal pain, diarrhea or distension) in 25%. Five patients (41.7%) developed septic shock, three requiring vasopressors and two mechanical ventilations. All had high AIGAs titres (1:2500) and hyper-inflammation (median WBC17.3×10⁹/L, CRP138.1mg/dL, PCT1.28ng/mL). Bacteraemia was present in 91.7% and mortality was 16.7% (2/12). Polymicrobial co-infection was universal; notably cytomegalovirus (50%) and TM (25%). Immunological profiling showed hyperglobulinaemia (IgG23.5±10.6g/L) and elevated IgE (257.5[79.7-598.2]IU/mL). Despite broad-spectrum antibiotics (83.3% survival), both fatalities occurred in patients who had not undergone NGS-based diagnosis.

Conclusion: This study is the first to define AIGAs-associated Salmonella infection as a distinct clinical syndrome, characterized by severe bacteremia, paradoxical hyperinflammation, universal polymicrobial coinfections, and immune dysregulation. Our findings underscore the critical importance of comprehensive pathogen detection, particularly via NGS, for timely diagnosis and improved patient outcomes.

Purpose: This study aimed to explore the resistance mechanisms and molecular characteristics of linezolid-non-susceptible Enterococcus faecium isolates (LNSEFM) from a tertiary hospital in Beijing, China, focusing on novel findings with significant clinical and epidemiological implications.

Patients and methods: LNSEFM strains isolated from clinical specimens between January 2011 and December 2023 were collected and screened for resistance genes, including rplC, rplD, rplV, 23s rRNA, optrA, poxtA, and cfr using polymerase chain reaction (PCR) and DNA sequencing. Molecular epidemiological analysis was performed using multi-locus sequence typing (MLST). Isolates carrying optrA and those harboring poxtA were subjected to whole-genome sequencing (WGS).

Results: Among 2384 clinical E. faecium isolates, 19 (0.80%) were linezolid-non-susceptible (MIC 4-32 mg/L). Among these, two vancomycin-resistant Enterococcus (VRE) strains exhibited an intermediate susceptibility to linezolid. Two distinct optrA variants (designated as KLDK and KLDP) were detected in separate LNSEFM isolates. The KLDK-positive isolate was found to co-harbor the vanM gene cluster despite maintaining vancomycin susceptibility. Additionally, one linezolid-resistant isolate carried a G2576T mutation in the 23S rRNA gene, whereas the other harbored the poxtA gene. MLST revealed 13 sequence types (STs) among the isolates, including a novel type ST2709.

Conclusion: This study identified key notable findings in LNSEFM: identification of linezolid intermediate VRE in China, clinical detection of the optrA KLDK variant in enterococci, optrA-vanM co-presence in vancomycin-susceptible E. faecium, and a novel sequence type (ST2709). These findings enrich our understanding of the molecular epidemiology of LNSEFM and provide critical insights into clinical antimicrobial management and infection control.

Purpose: This study aimed to evaluate the diagnostic accuracy and clinical applicability of metagenomic next-generation sequencing (mNGS) in pulmonary infections by comparing it with traditional culture methods in a Traditional Chinese Medicine (TCM) hospital setting.

Methods: This retrospective cohort study enrolled 67 consecutively admitted patients with radiologically and clinically confirmed pulmonary infections from the Department of Respiratory Infectious Diseases at Xinchang Hospital of Traditional Chinese Medicine between December 2022 and September 2024. Clinical specimens included blood, bronchoalveolar lavage fluid (BALF), sputum, hydrothorax and cerebrospinal fluid (CSF). mNGS and conventional culture were performed to compare detection rates and microbial community profiles.

Results: Among 67 cases, mNGS identified pathogens in 89.55% (60/67), compared to 20.90% (14/67) by traditional culture. Of 14 dual-positive cases, only 1 (1/14, 7.14%) showed complete concordance, while most exhibited discordance or partial genus-level overlap. mNGS further detected viral co-infections in 44.78% (30/67) and identified fastidious/non-culturable pathogens such as enterovirus, human herpesvirus type 1, and Mycobacterium tuberculosis. Patients with chronic diseases were more susceptible to EB virus infections.

Conclusion: mNGS significantly enhances pathogen detection in pulmonary infections, supports targeted antimicrobial therapy, and holds potential for contributing to clinical outcomes and reducing antibiotic resistance.

Background: Chlamydia abortus is a zoonotic pathogen that commonly causes abortion, pelvic inflammatory disease, or septicemia during pregnancy in humans. It can occasionally lead to pneumonia.

Case presentation: We report a 35-year-old male with pneumonia complicated by psychiatric symptoms and pneumomediastinum. Initial treatment with cefotaxime and piperacillin-tazobactam failed. On admission, chest CT revealed bilateral pulmonary inflammation, pneumomediastinum, and cervical subcutaneous emphysema. Bronchoalveolar lavage fluid underwent Targeted Next-Generation Sequencing, identifying Chlamydia abortus. Treatment with doxycycline and moxifloxacin led to resolution of fever, psychiatric symptoms, and pulmonary lesions. The patient continued oral doxycycline post-discharge, and follow-up CT showed near-complete recovery.

Conclusion: Chlamydia abortus infection can cause pneumonia with psychiatric symptoms, pneumomediastinum, and cervical emphysema-complications not previously reported. Targeted Next-Generation Sequencing (Targeted NGS) plays a crucial role in the early and precise detection of Chlamydia abortus, improving diagnostic accuracy and treatment timeliness. Doxycycline is effective in the treatment of Chlamydia abortus infection and contributed to the patient's recovery.

Background: Scedosporium aurantiacum is a rare opportunistic pathogen distributed worldwide. S. aurantiacum can cause invasive infections in both immunocompromised and immunocompetent individuals following exposure to contaminated environments. The risk associated with wastewater exposure is an important public health concern. Owing to its multi-drug resistance, the treatment of S. aurantiacum infection is very challenging.

Case presentation: We report a case of a 44-year-old Chinese male with disseminated infection and endocarditis caused by S. aurantiacum after falling into a nearly dry wastewater pool. S. aurantiacum isolated from blood cultures was identified using nanopore sequencing technology of internal transcribed spacer 1 (ITS1) and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS). In vitro antifungal susceptibility testing indicated that voriconazole was the most active agent with a minimum inhibitory concentration (MIC) of 0.5 μg/mL. Despite receiving appropriate antifungal therapy, the patient died 12 days after fungal isolation because of uncontrolled infection and systemic organ failure.

Conclusion: This is the first reported clinical case of S. aurantiacum endocarditis in China. This case highlights that even in immunocompetent patients, S. aurantiacum infection should be considered. For clinicians, understanding a detailed history of the contaminated environments that the patient has been exposed to is crucial for early diagnosis. Nanopore sequencing offers a new option for identifying S. aurantiacum. Drug susceptibility testing is essential for determining the most appropriate antimycotic agent.

Streptococcus pneumoniae (S.pn) is the predominant bacterial pathogen affecting children under 5 years old. Its polysaccharide capsule is the primary virulence factor, enabling the bacteria to evade the immune system and defining the serotypes that current vaccines target. Recently, nonencapsulated Streptococcus pneumoniae (NESp) have emerged as significant causes of conjunctivitis, otitis media, and invasive diseases worldwide. This report provides the first integrated genomic and phenotypic analysis of two NESp strains identified in China. The NESp colonies are characterized by their rough texture and small size, and they exhibit a slower growth rate compared to other serotypes. Whole-genome sequencing has identified these NESps strains as belonging to the ST10236 type. Notably, these strains demonstrate multidrug resistance. In comparison to encapsulated strains, NESps possess fewer coding genes related to cell wall biogenesis and basal metabolism. However, they still retain crucial virulence genes including the pspK gene. Our findings highlight the clinical significance of NESps and emphasize the need for ongoing surveillance of these "capsule-free" clones in the post-PCV era.

Purpose: Bloodstream infections (BSIs), a frequent and life-threatening complication during acute myeloid leukemia (AML) induction chemotherapy, carry high mortality; however, current predictive models lack robust combined inflammatory-metabolic biomarkers.

Patients and methods: We conducted a retrospective analysis of 225 AML patients (2020-2024). The systemic inflammation response index (SIRI) and lipids measured at baseline. BSIs were confirmed according to Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN) criteria during neutropenia. Predictors selected via univariate analysis (P<0.05) and multivariable logistic regression using backward selection based on the Akaike information criterion (AIC). A nomogram was constructed. Model validation included receiver operating characteristic curve analysis and area under the curve (ROC-AUC), calibration curves (1,000× bootstrap), and decision curve analysis (DCA).

Results: Among 225 AML patients, BSIs incidence was 24% (54/225). Patients with BSIs exhibited significantly elevated systemic inflammation (SIRI: 2.52 ± 0.38 vs 1.57 ± 0.29; P<0.001) and atherogenic dyslipidemia, characterized by higher low-density lipoprotein cholesterol (LDL-C: 3.43 ± 0.91 vs 2.56 ± 0.72 mmol/L; P<0.001) and lower high-density lipoprotein cholesterol (HDL-C: 0.61 ± 0.19 vs 0.92 ± 0.25 mmol/L; P<0.001). The SIRI-lipid nomogram incorporated six independent predictors, including SIRI (OR=3.36, 95% CI 2.00-6.07), LDL-C (OR=5.98, 95% CI 2.84-14.13) and HDL-C (OR=0.06, 95% CI 0.01-0.64). The nomogram achieved an AUC of 0.926 (95% CI 0.879-0.973) and demonstrated excellent calibration, with a mean absolute calibration error of 0.014 based on 1000 bootstrap samples. DCA showed clinical utility across decision thresholds. SIRI remained an independent predictor of BSIs after multivariable adjustment (OR=3.28) and correlated with prolonged hospitalization (P=0.007).

Conclusion: The SIRI-lipid integrated nomogram provides clinically applicable prediction of BSIs risk in AML induction therapy, with validated clinical utility. Elevated SIRI combined with atherogenic dyslipidemia, characterized by high LDL-C and low HDL-C, represents actionable risk indicators enabling early clinical interventions.

Introduction: The Sporothrix schenckii cell wall has been widely studied to understand its role in pathogenesis and the infection process. Previously, a component of the cell wall, the peptidorhamnomannan (PRM), was analyzed, and some proteins with unknown function were identified. Among them, the protein encoded by the SPSK_06559 gene stood out for its high abundance within PRM.

Methods: In this work, in silico analyses were performed to predict the adhesive properties of the SPSK_06559 protein (renamed as Pap2) to extracellular matrix (ECM) components, such as fibrinogen, fibronectin, and type-I and type-II collagen. Subsequently, a recombinant Pap2 (rPap2) version was generated to obtain experimental evidence of its adhesive properties to ECM components. Finally, the role of Pap2 in pathogenesis was assessed in Galleria mellonella larvae.

Results: Bioinformatic analyses consistently suggested that Pap2 possesses adhesive properties. Prediction was experimental validated: rPap2 showed strong adhesion to ECM components. Immunization with rPap2 conferred significant protection to G. mellonella larvae against a lethal dose of S. schenckii. Furthermore, preincubation of fungal cells with anti-rPap2 antibodies drastically reduced their ability to kill the larvae.

Discussion: These findings demonstrate that the SPSK_06559 protein (Pap2) participates in the initial adhesion to host tissues. Induction of a protective response through immune priming with rPap2 suggest that Pap2 is a promising immunogenic antigen. Reduction of lethality upon blocking Pap2 confirms its essential role in pathogenesis, positioning it as a potential target for the development of new therapies and vaccines against sporotrichosis.

Background: Given the limited treatment options for Acinetobacter infections due to drug resistance, timely and accurate diagnosis is crucial for effective management. This study evaluated the performances of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in identifying Acinetobacter bacteria.

Methods: Retrospective forty bacterial isolates from Thailand previously identified as A. baumannii using biochemical method were recruited. The retrospective diagnostic performances of biochemical method and MALDI-TOF MS were compared, considering whole-genome sequencing (WGS) as the reference standard.

Results: For identification performance, accuracy was 70% for the biochemical method, 82.5% for MALDI-TOF MS using direct colony samples, and 80% for MALDI-TOF MS using protein extract samples. In comparison to WGS, the direct colony method achieved the highest typing concordance. Regarding processing speed, MALDI-TOF MS effectively reduces the turnaround time compared to the biochemical method (p < 0.0001).

Conclusion: MALDI-TOF MS significantly outperforms biochemical method in the species-level identification of Acinetobacter. The superior efficacies in terms of accuracy, resolution, and speed emphasize the technical robustness of MALDI-TOF MS and position the method as an excellent identification technique for Acinetobacter isolates.

Introduction: The aim of this study was to detect lymphocyte subpopulations to discover potential immunologic indicators to differentiate active tuberculosis (ATB) from latent tuberculosis infection (LTBI) and healthy controls (HC) and to predict the risk of progression of LTBI to ATB.

Methodology: Flow cytometry was used to detect lymphocyte subsets in ATB, LTBI and HC to compare the differences in lymphocyte subpopulation levels between groups, and Logistic regression was used to screen ATB-related immune indices, development of a novel nomogram model to predict the risk of progression to ATB in individuals with LTBI.

Results: Compared to the LTBI group, the ATB group had significantly higher CD3⁺CD4⁺T cell percentage, whereas CD3^-CD16⁺CD56⁺NK cell percentage, lymphatic cell, CD3⁺T cell number, CD3⁺CD8⁺T cell number, and CD3^-CD16⁺CD56⁺NK cell number were significantly lower (P<0.05). Compared with the HC group, the ATB group had significantly higher CD3⁺T cell percentage and CD3⁺CD4⁺T cell percentage, whereas CD3^-CD16⁺CD56⁺NK cell percentage, lymphatic cell, CD3⁺T cell number, and CD3^-CD16⁺CD56⁺NK cell number were significantly lower (P<0.05); logistic regression analysis showed that CD3⁺CD4⁺T cell percentage, CD3⁺T cell number, and CD3⁺CD8⁺T cell number were all independent indicators for the diagnosis of ATB (P<0.05), and based on these three immune indicators, we constructed diagnostic feature to distinguish ATB and LTBI, ATB from HC, and successfully developed a novel nomogram model to predict the risk of progression to ATB in individuals with LTBI.

Conclusion: A combined assay of lymphocyte-associated immune markers serves as a biomarker for early ATB diagnosis in adolescents, and established a predictive model to evaluate the risk of progression of LTBI to ATB.