Frontiers in Cellular and Infection Microbiology最新文献

Objectives: Invasive Klebsiella pneumoniae liver abscess syndrome (IKPLAS) is a life-endangering condition. This meta-analysis sought to identify factors that could potentially serve as risk factors for IKPLAS.

Methods: Eight databases were retrieved. The Newcastle-Ottawa Scale and AHRQ criteria were utilized to assess the studies for quality. Stata software was used for pooling the effect size odds ratio (OR) and for subgroup analysis, sensitivity analysis, and regression analysis. Publication bias was examined leveraging funnel plots and Egger's test.

Results: A total of 18 studies (cross-sectional, cohort, case-control studies) were included, with 3,133 patients. The meta-analysis revealed that the following factors were linked to a significantly elevated risk of IKPLAS: history of smoking or alcohol consumption (OR = 1.61, 95% CI: 1.05, 2.45, p = 0.028), diabetes (OR = 1.93, 95% CI: 1.49, 2.51, p<0.001), liver disease (OR = 1.66, 95% CI: 1.01, 2.73, p = 0.044), elevated sequential organ failure assessment (SOFA) score (OR = 1.71, 95% CI: 1.27, 2.30, p<0.001), septic shock (OR = 3.30, 95% CI: 1.70, 6.37,p<0.001), hepatic abscess in the left lobe (OR = 1.51, 95% CI: 1.02, 2.24, p = 0.039), phlebitis (OR = 21.01, 95% CI: 10.24, 43.11, p<0.001), procalcitonin (PCT) (OR = 1.01, 95% CI: 1.01, 1.02, p<0.001), fasting blood glucose (FBG) (OR = 1.21, 95% CI: 1.11, 1.32, p<0.001), prothrombin time (PT) (OR = 1.15, 95% CI: 1.01, 1.30, p = 0.032), total bilirubin (OR = 1.02, 95% CI: 1.01, 1.02, p<0.001), hypervirulent phenotype (OR = 2.17, 95% CI: 1.15, 4.10, p = 0.017), K1 serotype (OR = 4.79, 95% CI: 1.79, 12.76, p = 0.002). No other risk factors were found.

Conclusion: This study identified multiple risk factors significantly associated with IKPLAS, providing evidence for risk assessment and prevention strategies.

Background: Infections due to multidrug- and extensively drug-resistant bacteria can be difficult to treat and are associated with high mortality and burden of disease. Ceftazidime-avibactam (CVA) is used in patients with multidrug-resistant Gram-negative bacterial infections.

Objective: To describe the real-world usage, effectiveness, and antimicrobial features of CVA in clinical practice in China.

Methods: This multicenter, prospective observational study collected medical record data from adult patients (≥18 years) who had been hospitalized and treated with ≥1 dose of CVA. Clinical and microbiological outcomes were evaluated at the end of treatment, with clinical cure defined as resolution of infection following treatment with CVA.

Results: Data were obtained from 220 adult patients receiving ≥1 dose of CVA in China. Infections indicated for CVA included pneumonia (64.5%), complicated intra-abdominal infection (16.8%) and bloodstream infection (7.3%). Klebsiella pneumoniae (129/227 isolates, 56.8%) was the most commonly identified pathogen, followed by Pseudomonas aeruginosa (33 isolates, 14.5%). Of 87 K. pneumoniae isolates, 76 (87.4%) were meropenem resistant and the same proportion carried cabapenemase genes. Low levels of resistance to CVA were observed across all isolates. Three-quarters of patients received CVA as definitive therapy. Clinical cure at end of treatment was achieved in 66.4% of patients and microbiological success in 69.6% of patients.

Conclusion: Findings from this study provide important real-world data on treatment patterns, microbiological features, and clinical and microbiological outcomes for CVA in routine clinical practice in China.

Objective: Through the machine learning Least absolute shrinkage and selection operator (LASSO) algorithm, the system screened core prognostic risk factors for patients with ischaemic stroke and bloodstream infection, constructed and validated a predictive model, provides a basis for formulating precise risk management strategies in clinical practice.

Methods: Clinical data from patients with bloodstream infections secondary to ischaemic stroke were retrospectively included. The dataset was randomly allocated into training and validation sets at a 7:3 ratio. Within the training set, Model 1 was constructed using traditional univariate and multivariate Cox regression methods, while Model 2 employed the machine learning LASSO regression algorithm. Models were compared using metrics including R-squared, C-index. The superior model was selected for validation on both training and validation sets using Area Under the Curve (AUC) of the receiver operating characteristic curve, calibration curves, and Decision-Making Curves (DCA).

Results: Model 2 was adopted as the final model, with a nomogram generated for the training set. As demonstrated by the nomogram, an increase in the total score was observed in patients with concomitant pneumonia, heart failure (HF), or coronary atherosclerotic heart disease (CHD), in cases where mechanical ventilation (MV) was utilised, and in instances of elevated alanine aminotransferase (ALT) and C-reactive protein-lymphocyte ratio (CLR) values, and reduced albumin levels. In the training set, the AUC values for predicting 7-day, 14-day, and 28-day survival rates were 0.875, 0.886, and 0.861, respectively. The AUC value for the 28-day prognosis on the internal test set was 0.844, while that on the external validation dataset was 0.860. The model demonstrated high concordance between predicted and actual probabilities across three distinct cohorts. The clinical decision curve indicates that the model provides good net benefit within the 5%-25% range at all three time points (7,14,and 28 days) across the three datasets.

Conclusion: Comorbidities such as pneumonia and hypoalbuminaemia constitute prognostic risk factors affecting patients with ischaemic stroke and bloodstream infections. LASSO regression enables precise identification of these risk factors, yielding a prognostic prediction model with outstanding predictive efficacy and clinical utility. Clinicians may utilise model variables to implement targeted risk management strategies.

Introduction: GII noroviruses (NoVs) are the leading cause of viral gastroenteritis worldwide. A critical unresolved question is whether natural infection elicits long-lasting protective antibodies, which is paramount for guiding vaccine development. The long-term persistence of functional neutralizing antibodies against the predominant GII genogroup remains poorly characterized.

Methods: In a 5-year community-based prospective cohort (2014-2018), we longitudinally assessed seroprevalence, seroincidence, and persistence of blockade antibodies against GII.4, GII.6, and GII.17 NoVs in 449 adults. HBGA (human histo-blood group antigen) associations with susceptibility were also analyzed.

Results: GII.4 exhibited the highest and most stable seroprevalence (77.3-79.7%), while GII.17 seroprevalence rose sharply from 41.9% to 72.2%, capturing its emergence as an epidemic strain. Seroincidence was substantial, highest for GII.17 (30.4 per 100 person-years). In contrast to GI NoVs, GII.4 and GII.17 antibody exhibited exceptional persistence, with five-year persistence rate of 94.5% for GII.4 and 81.4% for GII.17, respectively, and no significant decay in blockade activity-both significantly exceeding the 61.2% persistence of GII.6. HBGA susceptibility patterns were distinct: GII.4 and GII.6 were associated with secretor status and Lewis antigens, while only blood type A was linked to GII.17 susceptibility.

Conclusion: This study provides the first longitudinal evidence that natural infection with major GII NoVs, particularly GII.4 and the emerging GII.17, elicits robust and sustained functional antibody responses that persist for at least five years. This fundamental genogroup-specific disparity in immune durability, contrasting sharply with transient GI immunity, reveals a new dimension of NoVs immunology and provides a critical evidence base for the design of effective, long-lasting vaccines.

Background and aims: Fatty liver (FL) is a common comorbidity that has been associated with adverse clinical outcomes in various liver diseases. However, its impact on the prognosis of acute hepatitis B (AHB) remains unclear. This study aimed to evaluate the influence of FL on liver-related outcomes among hospitalized patients with AHB.

Methods: A retrospective analysis was conducted on hospitalized patients diagnosed with AHB from January 1, 2010, to December 30, 2023. Demographic and clinical data were collected, and patients were categorized into AHB with FL (AHB-FL) and AHB without FL (AHB-no FL) groups based on imaging and laboratory examinations. Multivariate regression models were utilized to investigate the association between FL and liver-related outcomes, including acute liver failure (ALF), hepatitis B surface antigen (HBsAg) loss, and seroconversion. Kaplan-Meier analysis was performed to assess differences in time to HBsAg loss and seroconversion.

Results: A total of 200 eligible patients were included, with 29 (14.5%) in the AHB-FL group and 171 (85.5%) in the AHB-no FL group. The incidence of ALF was significantly higher in the AHB-FL group (34.5% vs. 15.8%, P = 0.02). No significant differences were observed in rates of HBsAg loss (75.9% vs. 82.5%, P = 0.40) or seroconversion (44.4% vs. 53.1%, P = 0.40) between the two groups. Kaplan-Meier analysis indicated comparable times to HBsAg loss (P = 0.07) and seroconversion (P = 0.43). Multivariable analysis confirmed FL as an independent risk factor for ALF (OR 4.61, 95% CI 1.26-16.86; P = 0.02), but not for HBsAg loss (HR 1.60, 95% CI 0.92-2.78; P = 0.10) or seroconversion (HR 1.69, 95% CI 0.80-3.57; P = 0.17). Subgroup analysis indicated a stronger association between FL and ALF in rural patients (P interaction=0.02), suggesting regional differences may affect clinical risks and management.

Conclusion: FL constitutes a robust and independent determinant of ALF in AHB patients, sustained after rigorous adjustment for confounding factors. This evidence highlights a specific metabolic aggravation of liver injury, mandating the integration of FL screening into early risk stratification and management protocols.

Introduction: The reed vole, Microtus fortis, is the only known natural non-permissive mammalian host of Schistosoma japonicum. However, the molecular mechanisms underlying this resistance have not been fully understood.

Methods: We performed single-cell RNA-seq to investigate the peripheral blood mononuclear cells (PBMCs) responses to S. japonicum in M. fortis and the susceptible host, Kunming mice. The samples were collected from uninfected animals (control group) and infected animals at 10 dpi.

Results: The major cell types identified in the PBMCs of the two species were monocytes, dendritic cells (DCs), T cells, NK cells, B cells, and erythrocytes. We observed that the population of monocytes decreased considerably in the bloodstream after infection in both M. fortis and Kunming mice. However, differential gene expression analysis revealed that Cxcl9 was upregulated in M. fortis monocytes after infection, while it was not detected as a DEG in Kunming mice. In addition, we observed that infection induced the upregulation of IL2 and IL4 in M. fortis CD4+ T cells, and the expansion of the Th2 cell population. Regarding B cells, we did not observe any significant alteration among M. fortis B cell subpopulations after infection compared to the control. However, DEG analysis revealed that Igha, Ighg1, and Ighg3 were upregulated in M. fortis antibody secreting cells (ASCs) but not in Kunming mice.

Discussion: Together, our results suggest that both the innate and adaptive immune responses were activated in the peripheral blood of M. fortis at 10 dpi, while their activation was not obvious in Kunming mice at the same moment.

Objective: Sepsis remains a leading cause of intensive care unit (ICU) mortality worldwide, characterized by dysregulated inflammation and immune dysfunction mechanisms also central to many neglected tropical diseases. Omega-3 fatty acids (Ω-3 FAs) possess potent anti-inflammatory and immunomodulatory properties that may improve survival outcomes in such conditions. This retrospective real-world study evaluated the impact of Ω-3 FA supplementation on ICU mortality among patients with sepsis and identified prognostic factors influencing therapeutic efficacy.

Methods: Patients admitted with sepsis to the ICU of Shenzhen People's Hospital between December 2016 and July 2019 were retrospectively analyzed. Propensity score matching (PSM) was applied at a 1:2 ratio between Ω-3 FA-treated and control groups using covariates including age, sex, diagnosis, norepinephrine (NE) requirement, hemofiltration (HF), C-reactive protein (CRP), and lymphocyte count. Logistic regression and inverse probability of treatment weighting (IPTW) were performed to determine the independent effect of Ω-3 FAs on mortality.

Results: A total of 633 patients were included (Ω-3 FA group, n = 211; control, n = 422). The unadjusted mortality rate was 32.7% in the Ω-3 FA group and 24.6% in controls (p = 0.032). Univariate analysis showed a weak protective effect of Ω-3 FAs (HR = 0.74, 95% CI: 0.54-1.02, p = 0.062). After adjusting for age, HF and NE requirements, CRP, lymphocyte count, Sequential Organ Failure Assessment (SOFA) score, and abdominal infection, Ω-3 FAs demonstrated a significant protective effect (HR = 0.60, 95% CI: 0.43-0.83, p = 0.003). Kaplan-Meier analysis confirmed improved survival in the Ω-3 FA group (p = 0.038). Advanced age, elevated CRP, and higher NE dependence were identified as factors that negatively modulated Ω-3 FA efficacy.

Conclusion: Omega-3 fatty acid supplementation was associated with significantly reduced adjusted ICU mortality in sepsis, underscoring its host-directed immunomodulatory properties. These findings highlight the translational potential of Ω-3 FAs as adjunct therapeutic agents in sepsis and other infection-associated inflammatory disorders, supporting further drug development toward host-directed treatments for neglected tropical diseases.

Background: Although fungal infections are relatively rare, they have low detection rates and high mortality rates. The value of metagenomic next-generation sequencing (mNGS) in kidney transplant patients with fungal infections remains insufficiently explored, especially regarding diagnosis and antimicrobial stewardship.

Methods: From September 2021 to August 2023, 234 kidney transplant patients were enrolled, with detailed data collected on 66 patients suspected of fungal infections. The pathogen detection performance of mNGS and conventional microbiological tests (CMTs) was compared. The impacts of mNGS and CMTs on treatment adjustment were also assessed. Finally, the value of mNGS in detecting donor-derived infections was investigated.

Results: Among 66 patients, 21 fungal species were identified: 18 species detected by mNGS and 10 by CMTs. The overall positive rate of mNGS was significantly higher than culture (90.67% vs. 26.67%), especially for multiple fungal infections (9vs0). mNGS identified more Candida (26vs12), Pneumocystis jirovecii (14vs0), Aspergillus (10vs4), Mucor (6vs2) organisms compared with CMTs. Donor-derived fungi were identified in 11 (6.7%) patients, including 10 cases of Candida spp. and 1 case of Mucor spp. Anti-infection therapies were adjusted in 28 (24.4%) cases based on mNGS.

Conclusion: The mNGS technique showed distinct advantages in detecting fungal infections in kidney transplant patients, facilitating informed anti-infection strategies and enhanced graft protection. Moreover, it provides effective identification of fungal infections originating from donor sources.

The infective stages of apicomplexan protozoans, such as the malaria parasite Plasmodium, possess apical organelles rhoptries and micronemes, which contain secretory proteins required for host cell invasion. The mechanisms mediating invasion are largely conserved among apicomplexan parasites; for example, rhoptry proteins are secreted to form a tight junction prior to invasion, which facilitates parasite entry into target cells. Stage-specific invasion mechanisms have also been described; such as those differentially mediating Plasmodium merozoite infection of erythrocytes versus sporozoite stage invasion of mosquito salivary glands and mammalian hepatocytes. Sporozoites are the transmission stage present within the salivary glands of infected mosquitoes, and can efficiently infect the mammalian liver after being deposited in the skin during a blood meal. While some sporozoite rhoptry proteins have been demonstrated to be critical for invasion of mosquito salivary glands and mammalian hepatocytes, their comprehensive molecular mechanisms have not been elucidated due to the limited availability of material. To screen for Plasmodium sporozoite-specific rhoptry proteins in the rodent malaria parasite, Plasmodium berghei, a proximity-dependent biotin identification method was employed combined with a genome editing strategy. Rhoptry neck protein 12 (RON12) was identified as a rhoptry molecule with the highest transcript levels in sporozoites; and was selected for use as a bait following tagging with UltraID. In RON12::ultraID expressing transgenic sporozoites, several secretory proteins were successfully biotinylated during parasite maturation in mosquitoes, including known rhoptry proteins. A novel rhoptry molecule was identified, PBANKA_1363400, which was localized to sporozoite rhoptries and was predominantly expressed in sporozoites rather than merozoites. This study demonstrates that the UltraID strategy enables highly sensitive and comprehensive protein identification in a species- or stage-specific manner in Plasmodium sporozoites.