Infection and Drug Resistance最新文献

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.

Antifungal therapy for invasive pulmonary aspergillosis (IPA) can be challenging in cancer patients due to interpatient variability in pharmacokinetic properties of antifungals and potential drug-drug interactions (DDIs). This case report describes a 14-year-old boy with advanced osteosarcoma diagnosed with invasive pulmonary aspergillosis (IPA) after chemotherapy. Initial treatment of voriconazole showed poor improvement, as therapeutic drug monitoring (TDM) revealed exceptionally low trough concentration (0.28 μg/mL) even after dose increase. When voriconazole was switched to isavuconazole, favorable antifungal response was observed with isavuconazole trough concentrations ranging from 2.43 μg/mL to 4.12 μg/mL. Moreover, TDM also detected no obvious pharmacokinetic DDI between isavuconazole and apatinib but potential DDI between voriconazole and anlotinib in this patient. This case highlights the importance of individualized pharmacokinetic considerations in antifungal therapy in cancer patients. TDM may be a useful aid for therapeutic regimen decision and optimization.

Advances in diagnostic technologies have led to the identification of an increasing number of viruses associated with pneumonia, thereby drawing significant attention to viral pneumonia. The primary viral pathogens implicated in pneumonia include influenza virus, respiratory syncytial virus, coronavirus, adenovirus, parainfluenza virus, human metapneumovirus, and enterovirus. Post-translational modifications, especially phosphorylation, are pivotal in the lifecycle of these viruses. Phosphorylation affects key processes such as viral replication, transcription, assembly, and release, thereby influencing their propagation in host cells. Viral infection can also trigger kinase-associated pathways within host cells, activating host cell phosphatases and related signaling cascades. This results in alterations to host phosphorylation states, aggravating cellular pathology and facilitating viral proliferation. This review examines the common viral pathogens involved in pneumonia and highlights the role of phosphorylation in viral proliferation. Additionally, we explore the potential of phosphorylation inhibitors in controlling viral infections, with the aim of advancing our understanding of viral phosphorylation and promoting the use of these inhibitors in the treatment of viral pneumonia.

Background: Infections caused by daptomycin-resistant and vancomycin-resistant Enterococcus faecium (DRE) are a critical clinical challenge with limited therapeutic options. This study aimed to compare the efficacy of high-dose daptomycin monotherapy against combination therapies in a rat model of DRE infective endocarditis (IE).

Methods: A clinical DRE isolate (daptomycin MIC, 8 mg/L) was used to establish IE in Wistar rats. After 48  h, the animals were randomized to three-day regimens: saline control, daptomycin 90 mg/kg/day s.c. (D90), daptomycin 125 mg/kg/day s.c. (D125), D90 plus fosfomycin 500 mg/kg/day i.p. (D90F), or D90 plus ceftaroline 40 mg/kg q8 h i.m. (D90C). Efficacy was evaluated by quantifying colony-forming units (CFU) in excised cardiac vegetation.

Results: A strong correlation was observed between higher daptomycin exposure (Cmax/MIC and AUC_{0 -2 4}/MIC) and lower vegetation bacterial density (p < 0.01 for both). High-dose daptomycin monotherapy (D125) was the most effective regimen, resulting in the lowest mean vegetation bacterial load (4.75 log_{1 0} CFU/g). This was significantly lower than the bacterial load in the D90F group (5.62 log_{1 0} CFU/g; p = 0.02) and showed a trend towards superiority over the D90C group (5.87 log_{1 0} CFU/g; p = 0.05).

Conclusion: In this severe DRE infection model, escalating the daptomycin dose was more effective in clearing bacteria from the cardiac vegetation than combining a standard high dose with a synergistic agent. These findings suggest that higher daptomycin exposure may be a viable strategy for managing DRE infections, pending clinical validation.

Objective: To compare the clinical value of Group A Streptococcus (GAS) antigen detection and pathogen culture in the diagnosis and treatment of paediatric infections, providing a basis for the rational use of antibiotics.

Methods: This retrospective study included 310 paediatric patients with GAS infections admitted between January 2019 and January 2024. Patients were assigned to either the antigen-positive group (n = 156) or the culture-positive group (n = 154). Demographic characteristics, clinical features, treatment outcomes, and complications were compared between the two groups.

Results: There were no significant differences between the two groups in terms of demographic data (age, sex, weight) and clinical symptoms (such as fever, sore throat, and rash) (P > 0.05). The time to fever resolution (3.00 [3.00, 4.00] days vs 3.00 [2.00, 4.00] days, P = 0.103), time to sore throat resolution (3.00 [3.00, 5.00] days vs 4.00 [3.00, 5.00] days, P = 0.405), acute complication rates (6.41% vs 9.09%, P = 0.377), and late complications (none in either group) during the 3-month follow-up period showed no significant differences.

Conclusion: GAS antigen detection and pathogen culture have comparable clinical efficacy and can both effectively guide antibiotic treatment. Rapid antigen detection can be used as the preferred screening method in clinical practice, optimising early diagnosis and treatment.

Purpose: To examine the distribution of clinical pathogens and their antimicrobial resistance trends in a hospital in East China to provide evidence for rational antibiotic use and infection control.

Methods: We conducted a retrospective study of bacterial isolates from January 2020 to December 2024. Bacterial identification and antimicrobial susceptibility testing were performed using the VITEK 2 system. WHONET 5.6 and R software were used for data analysis. Statistical analyses included chi-square tests and trend tests.

Results: A total of 8680 pathogenic isolates were collected. Gram-negative bacteria predominated (74.7%) over Gram-positive bacteria (25.3%). The primary specimens were urine (33.7%), sputum (25.3%), and secretions (19.4%). The leading pathogens were E. coli (28.4%), K. pneumoniae (12.8%), and P. aeruginosa (11.5%). The carbapenem resistance rate was less than 1.9% in Escherichia coli strains over five years. The rate for carbapenem resistant K. pneumoniae (CRKP) showed a significant increasing trend, rising from 9.4% in 2022 to 16.7% in 2024 (p<0.05). CRKP rates were lower than national CHINET data. The imipenem resistance rate of Pseudomonas aeruginosa exhibited an upward trend from 2020 (24.2%) to 2023 (34.1%) (p<0.05). A. baumannii maintained high resistance to imipenem (>73%), exceeding national levels. The proportion of methicillin-resistant Staphylococcus aureus (MRSA) fluctuated over the course of the five years (26.9-44.8%). No vancomycin-resistant Enterococcus (VRE) was detected.

Conclusion: E. coli, K. pneumoniae, and P. aeruginosa were the predominant pathogens in this hospital. The rising and high resistance rates of CRKP and CRAB highlight the urgent need for enhanced antimicrobial stewardship. Β-lactamase, β-lactamase inhibitor combination preparations and carbapenems were recommended for susceptible strains of E. coli and K. pneumoniae. For CRKP infections and CRAB infections, tigecycline and colistin are recommended. Continuous surveillance and infection control are crucial to combat the evolving threat of multidrug-resistant organisms.

Objective: This study reports five clinical cases of adult Febrile Infection-Related Epilepsy Syndrome (FIRES) treated with a ketogenic diet (KD). The aim is to explore the clinical efficacy, safety, optimal initiation timing, and related efficacy factors of KD in adult FIRES through case analysis, and to provide reference for clinical decision-making.

Methods: We retrospectively reviewed the medical records of five FIRES patients treated with KD at Shanxi Bethune Hospital between October 2019 and January 2025.

Results: Among the five FIRES patients (2 males, 3 females), with a median age of 32 years [interquartile range (IQR) 25-34]. All patients presented with refractory status epilepticus following a febrile illness. EEG revealed slowed background activity with multifocal epileptiform discharges, and 60% (3/5) showed abnormal brain MRI findings. All patients received multidrug antiseizure therapy, anesthetics, and immunotherapy. KD was initiated at a median of 33 days (IQR 10-50) post-onset. Ketosis was achieved within a median of 2 days (IQR 2-3), followed by significant seizure reduction after a median of 3 days (IQR 3-4) of KD. At discharge, mRS scores were 2 (40%) or 4 (60%); by 3-month follow-up, all patients achieved an mRS score of 2. Common adverse effects included diarrhea (60%), hypoalbuminemia (100%), anemia (80%), fecal occult blood (60%), and hyperlipidemia (40%), all of which resolved with symptomatic management.

Conclusion: FIRES is a rare and devastating clinical syndrome with an unclear pathogenesis, high mortality, and poor prognosis, often accompanied by cognitive decline or severe neurological sequelae. KD appears effective in FIRES management; however, due to limited case data, further large-sample, prospective, or randomized controlled studies are needed to elucidate its short- and long-term efficacy in adult FIRES patients.