Infection and Drug Resistance最新文献

Purpose: Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease characterized by high mortality rate. This study aimed to explore the predictive ability of the red blood cell distribution width to albumin ratio (RAR) for mortality risk in SFTS.

Patients and methods: A total of 650 hospitalized SFTS patients from two centers were randomly assigned to a training (N = 455) and validation (N = 195) cohort at a 7:3 ratio. Independent risk factors were identified by constructing the LASSO regression model and Cox regression model. The predictive power and clinical benefit of risk factors were assessed using receiver operating characteristic (ROC) and decision curve analysis (DCA), respectively, with the nomogram visualizing the model. Kaplan-Meier curve and the Log rank test were employed to compare survival probabilities.

Results: The 650 patients had a median age of 66 years. Deceased exhibited a significantly higher RAR value than survivors (4.61 vs 3.77, P < 0.001). The RAR, neurological manifestations, and viral load were identified as independent risk factors for death in SFTS patients by multivariate Cox regression analysis, and the model was subsequently visualized using a nomogram. RAR demonstrated the strongest predictive performance (AUC: 0.845, P < 0.001), outperforming neurological manifestations (AUC: 0.636, P < 0.001) and viral load (AUC: 0.805, P < 0.001). In the validation cohort, RAR achieved an AUC of 0.824. Kaplan-Meier survival analysis demonstrated that SFTS patients who have RAR > 4.19 (Log rank test; χ² = 67.43, P < 0.001) experienced significantly lower survival rates. DCA demonstrated that the RAR had clinical net benefit for predicting mortality in SFTS patients.

Conclusion: Baseline higher RAR levels were associated with an increased risk of death in SFTS patients. RAR may serve as a valuable predictor of mortality in SFTS patients during the early stage of disease.

Background: The transmission of carbapenem-resistant Pseudomonas aeruginosa (CRPA) between hospital environment and patients poses significant challenges for clinical management. The COVID-19 pandemic may have influenced bacterial transmission dynamics in intensive care units (ICU). This study aimed to prospectively investigate the temporal and spatial spread of P. aeruginosa after a COVID-19 upsurge period in China.

Methods: We routinely screened for P. aeruginosa in both the environment and patients in a newly-opened 21-bed tertiary teaching hospital ICU in eastern China from October 2022 to April 2023, during which a COVID-19 upsurge occurred from December 2022 to January 2023. Whole-genome sequencing and antibiotic susceptibility testing were performed on all non-repetitive P. aeruginosa isolates.

Results: Among 1694 environmental samples, 40 (2.36%) samples were CRPA. In 1576 nasopharyngeal and rectal samples (from 353 patients), 108 samples (6.86%) were CRPA. Sequence type (ST) 463 was the most prevalent clone in both patient and environmental samples. Spatiotemporal distribution and genomic data revealed sporadic patients-related transmission before COVID-19 upsurge period, while high-risk ST463 clone transmission was detected during COVID-19 upsurge period. However, there was no strong evidence to show that antibiotic consumption significantly influenced CRPA transmission in this study. Additionally, the evolution events of bla _KPC (from bla _KPC-2 to bla _KPC-71) were observed, resulting in multi-sites CRPA colonization in one patient.

Conclusion: Our prospective study demonstrates that COVID-19 upsurge is associated with increased P. aeruginosa transmission. These findings provide valuable insights into nosocomial infection management during future public health crisis. We also reported carbapenemase mutation from bla _KPC-2 to bla _KPC-71 in P. aeruginosa, which provides reference for further antibiotic usage.

Purpose: The development of metabolic dysfunction-associated steatotic liver disease (MASLD) in people living with HIV (PLWH) is more complex than in the general population. Despite this, PLWH are often excluded from large-scale MASLD studies. This study aims to develop and validate a nomogram for predicting the risk of MASLD in PLWH.

Patients and methods: This retrospective cohort study included PLWH who attended the outpatient clinic at Ningbo Hospital of Integrated Traditional Chinese and Western Medicine. A total of 717 participants were randomly assigned at a ratio of 7:3. Least absolute shrinkage and selection operator (LASSO) regression was employed to identify significant predictors of MASLD. A multivariable Cox regression model was then utilized to develop a nomogram for predicting the risk of MASLD. The performance of the nomogram was assessed using the concordance index (C-index), receiver operating characteristic curve, calibration plots, and decision curve analysis (DCA). Competing risk analysis was conducted to further validate the identified predictors.

Results: The LASSO regression analysis identified eight independent predictors, including the antiretroviral therapy regimen, alanine aminotransferase, serum amylase, uric acid, triglycerides, high-density lipoprotein cholesterol, and CD4 and CD8 T lymphocyte counts. The Area Under the Curve (AUC) for 1-, 3-, and 5-year outcomes in the development cohort ranged from 0.793 to 0.830, while the validation cohort exhibited AUC ranging from 0.749 to 0.903. Calibration plots confirmed a robust agreement between the predicted and observed outcomes. The C-index and DCA indicated the superior prediction performance of the nomogram. This relationship remained statistically significant after using the competing risk analysis.

Conclusion: This study developed the first clinical nomogram specifically for PLWH based on the 2023 MASLD definition. The model is based on eight clinically accessible and objective variables, including HIV-specific parameters, and is intended for the early screening of MASLD within this population.

Introduction: Candida auris poses a global public health threat due to its multidrug resistance and association with severe invasive infections. With limited treatment options, combination therapies are being explored to enhance antifungal efficacy. This study aimed to evaluate the in vitro synergistic activity of anidulafungin combined with isavuconazole, voriconazole, posaconazole, and amphotericin B against clinical C. auris isolates.

Methods: Fifty clinical C. auris isolates were identified via MALDI-TOF MS. Antifungal susceptibility testing was performed using the EUCAST broth microdilution method to determine Minimum Inhibitory Concentrations (MICs). Subsequently, the in vitro interactions of anidulafungin with four other antifungals were assessed using a checkerboard assay. Drug interactions were classified by calculating the Fractional Inhibitory Concentration Index (FICI).

Results: High resistance rates were observed for fluconazole (72%) and amphotericin B (48%), whereas no isolates were resistant to echinocandins. In combination tests, interactions were predominantly indifferent (56-84%), followed by partial synergy (12-40%). A single instance of true synergy (FICI = 0.49) was noted with the anidulafungin-posaconazole combination in one isolate. Synergy rates (synergy + partial synergy) varied significantly across combinations (Fisher's exact test, p = 0.0044), with anidulafungin-azole combinations showing the highest rates (36-40%) compared to anidulafungin-amphotericin B (12%). No antagonism (FICI ≥ 4) was detected in any combination.

Discussion: The predominance of indifferent interactions, with some partial synergy, suggests that combination therapy may not consistently offer a strong synergistic benefit for these isolates. This exploratory study characterizes the in vitro interaction landscape in our isolate collection, providing foundational data to guide future research and inform clinical decisions where treatment options are scarce.

Purpose: Bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) after liver transplantation (LT) is a rising threat during postoperative care. An alternative antibiotic treatment approach comprises ceftazidime-avibactam. This retrospective cohort study evaluated a novel ceftazidime-avibactam-centered bundle therapy (CCBT) for CRKP BSIs in LT recipients.

Patients and methods: Among 728 LT recipients, 25 patients with CRKP BSIs were included. The CCBT comprised: (1) prompt infection source control; (2) early ceftazidime-avibactam initiation (<3 days post-culture); (3) immunosuppression adjustment (discontinuation of calcineurin/mechanistic target of rapamycin inhibitors/mycophenolate until blood culture clearance); and (4) intravenous immunoglobulin (IVIG, 300 mg/kg/day for 5 days). The controls received empirical anti-infection therapy comprising polymyxin- and tigecycline-based combination regimens, or amikacin and polymyxin used in combination with meropenem according to drug susceptibility results. Outcomes included microbiological clearance, mortality, immune/liver function recovery, recurrence, and complications.

Results: Patients were distributed into CCBT (n=15) and control (n=10) groups. The CCBT group had a higher blood culture clearance rate (100% vs 50%; P=0.005) and longer post-infection median survival time (407 vs 18.5 days; P=0.011) than the control group. Liver enzyme (aspartate aminotransferase, alanine aminotransferase, direct bilirubin) levels improved significantly (P<0.05) and normalized in the CCBT group. The CCBT group also exhibited significant rebounds in natural killer, CD4+, and CD8+ cell numbers post-recovery (P<0.01), indicating immune reconstitution. Despite immunosuppression withdrawal, rejection occurred in only 2 CCBT group patients (Banff scores 3 and 5), which were managed successfully with steroid pulses. Perioperative complications (bile leaks, hepatic artery issues) showed no intergroup differences.

Conclusion: A multidisciplinary bundle integrating ceftazidime-avibactam, IVIG and immunosuppression minimization significantly improved survival and microbiological outcomes in patients with CRKP BSI after LT, compared with antibiotic therapy alone. Multicenter studies are merited to confirm whether wider implementation of this multidisciplinary bundle would improve outcomes in patients with CRKP BSI after LT.

Purpose: Ventilator-associated pneumonia (VAP) is a common complication in intensive care units (ICUs) with high mortality rates. Early risk stratification is often limited by the lack of availability of complex prognostic scoring and microbiology turnaround time. This study aimed to assess the neutrophil-to-lymphocyte ratio (NLR) and systemic inflammatory response index (SIRI) on the day of VAP diagnosis as predictors of in-hospital mortality.

Patients and methods: We conducted a retrospective cohort study using secondary data from mechanically ventilated adult patients with VAP admitted to Hasan Sadikin General Hospital (a tertiary referral hospital in Bandung, Indonesia) from January 1, 2021 to December 31, 2022. VAP was confirmed by chart review using standard clinical and radiologic criteria occurring ≥48 hours after the start of mechanical ventilation, with endotracheal aspirate culture when available. The primary outcome was all-cause in-hospital mortality (death before hospital discharge). NLR and SIRI were calculated from the first complete blood count on the day of VAP diagnosis. Optimal cut-offs were determined using ROC analysis (Youden index). Survival was analyzed from VAP diagnosis until death or discharge.

Results: Among 87 patients, 68 died in hospital and 19 survived to discharge. NLR had excellent discriminatory power for in-hospital mortality (AUC 0.981); a cut-off >11 had 100% sensitivity and 89.5% specificity. SIRI had good discriminatory power (AUC 0.860); a cut-off >16 had 64.7% sensitivity and 100% specificity. In univariable Cox models, NLR >11 was associated with increased mortality risk (HR 29.07; 95% CI 2.24-376.92), whereas SIRI >16 showed a non-significant trend (HR 1.55; 95% CI 0.93-2.57).

Conclusion: NLR and SIRI obtained on the day of VAP diagnosis are simple, non-invasive laboratory markers that could aid in early risk stratification for in-hospital mortality in VAP. These markers should not replace but rather complement established clinical severity assessment and treatment decisions.

Purpose of review: Concurrent HIV and hepatitis B virus (HBV) affect an estimated 4-5 million people worldwide and remain a major driver of liver-related morbidity and mortality, even among individuals receiving tenofovir-containing antiretroviral therapy (ART). Both viruses establish long-lived reservoirs that are not eliminated by current antiviral therapies. This review summarizes current mechanistic and clinical frameworks for understanding concurrent HIV and HBV, highlights the interplay between their viral reservoirs, and discusses the implications of these interactions for cure strategies.

Recent findings: The liver functions as a multicellular reservoir. HBV persists within hepatocytes as nuclear covalently closed circular DNA (cccDNA) and integrated viral sequences. HIV persists as integrated provirus in tissue-resident CD4⁺ T cells and liver macrophages, with evidence supporting viral transfer or cell-to-cell spread involving stellate cells and hepatocytes. Concurrent HIV and HBV accelerate fibrosis and immune dysfunction through shared pathogenic pathways, including epigenetic silencing, cytokine- and checkpoint-mediated T-cell exhaustion, metabolic stress, and inflammation driven by the gut-liver axis. HBV-associated liver injury promotes recruitment of HIV target cells, while HIV-associated immune dysregulation impairs HBV control. Despite these interlinked biological mechanisms, individuals living with HIV and HBV are frequently excluded from clinical trials, slowing therapeutic progress and exacerbating health inequities.

Summary: Concurrent HIV and HBV represent a synergistic disease model that demands integrated therapeutic approaches and inclusive research frameworks. Priority needs include robust tissue-based reservoir measurements, validated biomarkers that distinguish latent from transcriptionally active viral states, combination strategies incorporating antiviral, antifibrotic, and immunomodulatory agents, and community-engaged clinical trial designs that are inclusive of individuals living with HIV and HBV and safe in the context of HBV. Advancing these areas will be essential to achieving durable remission-and ultimately functional cure-for both viruses.

Purpose: The aim of this cross-sectional study was to evaluate the environmental-human interface of antimicrobial resistance (AMR) by investigating drug-resistant bacteria in hospital air and the nasal microbiota of healthcare personnel across four tertiary care hospitals in Pakistan.

Material and methods: A total of 80 samples (40 aerosol samples and 40 nasal swabs) were collected and analyzed using culture-based microbiological identification. Antimicrobial susceptibility testing was performed using the Clinical & Laboratory Standards Institute-guided disc diffusion method, and polymerase chain reaction (PCR) was used to screen representative β-lactam-resistant isolates for key resistance genes, including blaZ, blaI, CTX-M, and SHV.

Results: Bacterial isolates were categorized into three ecological groups: environment-exclusive strains (eg, Escherichia coli detected only in aerosols and viridans streptococci detected only in nasal samples), co-existing strains prevalent in both niches (notably Staphylococcus aureus and Staphylococcus epidermidis), and strains showing marked differential prevalence between environments (eg, Serratia marcescens predominant in aerosols and Enterococcus spp. in nasal samples). A high proportion of isolates exhibited resistance to multiple antibiotic classes, consistent with multidrug-resistant (MDR) phenotypes, while resistance patterns suggestive of extensive drug resistance were observed in selected isolates. Molecular analysis confirmed the presence of clinically relevant β-lactamase genes, including blaZ/blaI in aerosol-derived S. aureus and CTX-M/SHV in nasal Klebsiella pneumoniae.

Conclusion: These findings demonstrate that hospital air acts as not only a reservoir for environmental pathogens but also a potential conduit for microbial exchange with healthcare personnel. Therefore, integrated infection control strategies incorporating air quality management and personnel surveillance are essential. As the interpretation of the findings is limited by the cross-sectional design and reliance on culture-based methods, future studies should include longitudinal and molecular-based approaches.

Background: Community-acquired pneumonia (CAP) represents a substantial global health burden; however, the characteristics of its etiological spectrum remain incompletely defined. Targeted next-generation sequencing (tNGS) has significantly advanced the understanding of the etiological spectrum. This study aimed to investigate the pathogen characteristics in CAP patients across different age groups and severity levels based on tNGS results.

Methods: We retrospectively analyzed the etiological test results of 272 hospitalized CAP patients at the First Hospital of Shanxi Medical University (Taiyuan, China) from 2021 to 2024. Patients were stratified by age and Pneumonia Severity Index (PSI) score, and their clinical characteristics, etiological spectrum, and infection patterns were systematically evaluated.

Results: Among the 145 patients included in the final analysis, 34.48% had simple infections, while 65.52% had multiple infections. Elderly patients (≥80 years) exhibited the highest proportion of mixed infections (81.82%), with the detection rates of viruses and fungi-such as Epstein-Barr virus, Human herpesvirus 5, Candida glabrata, and Candida albicans-increasing significantly with advancing age. Younger patients (18-39 years) were more susceptible to atypical pathogen infections (eg, Mycoplasma pneumoniae). The proportion of mixed infections in severe cases was significantly higher than that in mild cases (76.92% vs 59.14%), and triple co-infections (involving bacteria, viruses, and fungi) were significantly concentrated in the severe group. Significant specific differences in the composition of the etiological spectrum were also observed among different age and severity groups; for instance, the detection rates of Klebsiella spp. and Acinetobacter baumannii were higher in the elderly and severe groups, whereas atypical pathogens were mainly concentrated in the young group.

Conclusion: The etiological spectrum of CAP exhibits significant differences across different age groups and disease severity levels. Therefore, stratified diagnosis and therapeutic strategies should be developed based on age and disease severity to optimize prognosis and reduce the misuse of antibiotics.

Plasma microbial cell-free DNA sequencing (mcfDNA-seq) has emerged as a promising diagnostic and prognostic tool for infectious diseases, with early enthusiasm driven by its potential to outperform conventional microbiological assays in detection sensitivity. However, its anticipated clinical superiority has not consistently translated into transformative improvements in infection management, particularly in high-risk populations. Since its inception in 2015, key controversies have persisted regarding the optimal timing of mcfDNA-seq testing, clinical utility of longitudinal quantification, preferred testing modality (plasma mcfDNA-seq vs blood cell DNA sequencing), and integrative analysis of mcfDNA-seq data incorporating host immune biomarkers and antimicrobial resistance (AMR) gene profiling to enhance diagnostic precision. To address these unresolved questions, this review synthesizes the current evidence on the clinical applications of plasma mcfDNA-seq, critically evaluates its performance across diverse infectious disease contexts, and concludes by delineating future challenges and opportunities to optimize its translational utility for clinical practice.