Infectious Diseases and Therapy最新文献

Introduction: Adults with certain comorbidities, including metabolic and cardiopulmonary diseases, are at increased risk of severe respiratory syncytial virus (RSV) disease. We evaluated the cost-effectiveness of adjuvanted RSVPreF3 vaccination in adults in the USA aged 50-59 years at increased risk of severe RSV.

Methods: A Markov model with a 5-year time horizon estimated health and cost outcomes associated with adjuvanted RSVPreF3 vaccination in 3,259,715 adults aged 50-59 years with chronic obstructive pulmonary disease (COPD) from a societal perspective, compared with no vaccination. Inputs related to epidemiology, vaccine efficacy, and demographics came from published literature and public sources; assumptions, when needed, relied on expert consultation. A 46.2% vaccine uptake was assumed, on the basis of influenza vaccination. We reported incremental public health impact, costs, quality-adjusted life years (QALYs) lost, and incremental cost-effectiveness ratios. Scenario analyses investigated outcomes in adults aged 50-59 years with heart failure (HF), coronary artery disease (CAD), diabetes, or asthma.

Results: Over a 5-year time horizon, one-time adjuvanted RSVPreF3 vaccination of 1,505,989 adults aged 50-59 years with COPD was projected to prevent 163,181 RSV acute respiratory illness cases, 126,565 lower respiratory tract disease cases, 11,609 RSV-related hospitalizations, 4117 emergency department visits, 816 deaths, and 12,144 QALY losses, compared with no vaccination. Adjuvanted RSVPreF3 vaccination was a cost-saving strategy (i.e., dominant) versus no vaccination in US adults aged 50-59 years with the modeled comorbidities, reducing societal costs and improving health outcomes in each scenario.

Conclusions: In US adults aged 50-59 years at increased risk of severe RSV, a single dose of adjuvanted RSVPreF3 vaccination was projected to improve public health outcomes at a lower societal cost compared with no vaccination. Efforts are needed to ensure access to vaccination for populations at increased risk of severe RSV disease.

Sepsis and acute kidney injury (AKI) are significant contributors to morbidity and mortality in neonates, infants, and children. This comprehensive review aimed to evaluate the application of metabolomics in the challenging diagnostic process of sepsis and AKI in neonatal and pediatric populations. We highlighted the role of metabolomic profiling in enabling the accurate identification of biomarkers associated with sepsis and AKI, allowing for the timely prevention or detection of the disease. Additionally, pharmacometabolomics was presented to ascertain the contribution of metabolomics towards optimizing an individual's drug therapy via direct measurement and monitoring of drug metabolites to predict the pharmacokinetic profiles of drug compounds. This review also addressed the obstacles in translating metabolomic research into clinical practice, including the need for standardized methodologies, age-specific reference data, and large-scale validation studies as a result of the current limited literature in this area. Ultimately, the review showcased how utilizing metabolomics-driven diagnostic and treatment guidelines can promote positive clinical outcomes in infants and children affected by sepsis-associated AKI.

Introduction: EPIC-IC was a randomized, double-blind trial comparing the approved 5-day regimen of nirmatrelvir-ritonavir (NMV/r) vs. 10-day and 15-day NMV/r in immunocompromised individuals with mild-to-moderate COVID-19. We describe patient-reported global impressions of illness from EPIC-IC.

Methods: In EPIC-IC, 155 immunocompromised participants received 5-day, 10-day, or 15-day NMV/r (1:1:1). Participants completed the Global Impressions Questionnaire through week 24. Median times to first alleviation and resolution of symptoms and return to usual health and usual activities were estimated using Kaplan-Meier analyses for each treatment arm and post hoc subpopulations with severe vs. non-severe immunocompromise. Five-day arm times were compared vs. 10-day and 15-day arm times.

Results: Symptoms were alleviated after a median 6.0 (95% CI 4.0-9.0) days with 5-day NMV/r, similar to 9.0 (5.0-9.0) days with 10-day NMV/r (p = 0.627) and 10.0 (6.0-11.0) days with 15-day NMV/r (p = 0.528). Symptoms resolved after a median 16.0 (10.0-22.0) days with 5-day NMV/r, similar to 13.0 (9.0-14.0) days with 10-day (p = 0.140) and 13.0 (11.0-21.0) days with 15-day NMV/r (p = 0.471). In the severely immunocompromised subpopulation, symptoms resolved later with 5-day vs. 10-day NMV/r (p = 0.026). Participants returned to usual health after a median 11.0 (6.0-16.0) days with 5-day NMV/r, similar to 9.0 (6.0-13.0) days with 10-day (p = 0.319) and 10.0 (6.0-13.0) days with 15-day NMV/r (p = 0.218), and to usual activities after 10.0 (9.0-15.0) days with 5-day NMV/r, similar to 9.0 (6.0-10.0) days with 10-day (p = 0.102) and 9.0 (5.0-10.0) days with 15-day NMV/r (p = 0.190).

Conclusions: Times to symptom alleviation/resolution and returns to usual health/activities were similar with 5-day vs. extended NMV/r and comparable to those in the EPIC-HR trial. Five-day treatment may be adequate for most immunocompromised individuals, while extended treatment might improve symptom resolution in those with severe immunocompromise; larger studies are needed to confirm these findings.

Trial registration: ClinicalTrials.gov identifier, NCT05438602.

Introduction: The complex pathophysiology and diverse clinical manifestations of sepsis and septic shock continue to make early diagnosis and severity assessment challenging. Previous studies revealed the distinct roles of histone H3 lysine 18 lactylation (H3K18la) and H3 lysine 18 acetylation (H3K18ac) in infection. However, the functions and interactions of these modifications remain unclear. This study aimed to investigate the expression and roles of H3K18la and H3K18ac in patients with sepsis and septic shock.

Methods: This ambispective cohort study enrolled 86 critically ill patients (13 sepsis, 37 septic shock, and 36 noninfectious) and 12 healthy volunteers. Baseline information and laboratory data were collected. H3K18la and H3K18ac levels in peripheral blood mononuclear cells were detected via Western blotting. Serum cytokines, arginase-1 (ARG1), and Krüppel-like factor 4 (KLF4) mRNA were assayed via microsphere immunofluorescence and quantitative real-time polymerase chain reaction. The potential value of H3K18la, H3K18ac, and their ratio (H3K18la/ac) in the diagnosis and severity assessment was analyzed using logistic regression, receiver operating characteristic curve, and correlation analysis.

Results: Compared with the noninfectious group, the infectious group presented increased H3K18la and H3K18la/ac and decreased H3K18ac levels, with H3K18la/ac as an independent diagnosis biomarker. Compared with the sepsis group, the septic shock group presented higher H3K18la and H3K18la/ac and lower H3K18ac levels. H3K18la and H3K18la/ac levels correlated positively with sequential organ failure assessment (SOFA) scores, length of intensive care unit (ICU) stay, and mechanical ventilation time. H3K18ac levels correlated negatively with SOFA scores and mechanical ventilation time. H3K18la levels correlated negatively with interferon-α (IFN-α) and interleukin‑5 (IL‑5) and positively with IL-10 expression. H3K18ac levels correlated negatively with IL-6, IL-1β, IL-8, and IL-10 expression. H3K18la/ac levels correlated negatively with IFN-α and IL-5 and positively with IL-6, IL-8, and IL-10 expression. H3K18la and H3K18la/ac correlated positively, whereas H3K18ac correlated negatively with ARG1 and KLF4 mRNA expression.

Conclusions: H3K18la, H3K18ac, and H3K18la/ac can serve as biomarkers for the diagnosis and severity assessment of sepsis and septic shock through their involvement in inflammatory responses and macrophage polarization, thereby informing targeted therapies to modulate immune responses and improve patient outcomes.

Introduction: Post-acute sequelae of COVID-19, often referred to as "long COVID," have raised concerns about increased healthcare utilization following hospitalization. Whether these patterns differ significantly from those observed after other acute respiratory infections (ARIs) remains unclear. This study aimed to compare post-discharge healthcare use between patients hospitalized for COVID-19 and those with other ARIs in Lombardy, Italy.

Methods: We conducted a population-based cohort study using 2021 administrative healthcare data from the Lombardy Region. Patients aged ≥ 40 years hospitalized for COVID-19 or other ARIs were followed for 12 months post-discharge. We evaluated specialist consultations, rehospitalizations, diagnostic testing, and new chronic drug treatment initiations. Logistic regression models adjusted for age, sex, and comorbidities (Drug-Derived Complexity Index) were used to assess differences.

Results: Among 57,795 patients, 35,458 were hospitalized for COVID-19 and 21,375 for other ARIs. Patients with COVID-19 were younger and had lower comorbidity burden and post-discharge mortality (10.7% vs. 33.5%). A higher proportion received at least one specialist visit (75.8% vs. 70.3%), though with a longer median time to first visit (63 vs. 45 days, p < 0.0001). Patients with COVID-19 had more frequent imaging and spirometry but initiated fewer chronic drug treatments overall. However, a higher prescription rate for antidiabetics (OR 1.42), psychoanaleptic (OR 1.21), and genitourinary/hormonal drugs (OR 1.29) emerged after COVID-19 hospitalizations: this rate remained statistically higher for antidiabetics even after excluding subjects who died in the year following discharge. Hospitalizations for causes other than COVID-19 were more frequent in patients with ARI.

Conclusions: Compared to other ARIs, COVID-19 survivors exhibited distinct post-discharge healthcare patterns, with delayed but focused specialist care and selective increases in diagnostic and pharmacological interventions.

Introduction: The aim of this study was to assess the relative vaccine effectiveness (rVE) of cell-based versus egg-based quadrivalent influenza vaccines (QIVc versus QIVe) in preventing test-confirmed influenza during the 2023-2024 US influenza season.

Methods: rVE was estimated using a test-negative design applied to a large, linked, real-world dataset. QIVc or QIVe recipients aged 6 months-64 years who were tested for influenza within ± 7 days of an acute respiratory or febrile illness were included. rVE was estimated using doubly robust logistic regression. Analyses were performed for the full, pediatric, adult, outpatient and high-risk populations and by influenza type. Public health impact was assessed using a compartmental influenza burden averted model.

Results: The analysis included 2119 QIVc-cases, 14,750 QIVc-controls, 14,559 QIVe-cases, and 75,351 QIVe-controls. QIVc was superior to QIVe in preventing test-confirmed influenza with an rVE of 19.8% (95% CI 15.7-23.8%) in the full population, and with rVEs of 19.6% (13.6-25.3%) in the pediatric population aged 6 months-17 years and 18.5% (12.1-24.5%) in adults aged 18-64 years. Consistent results were observed for all sensitivity and subgroup analyses against any influenza. If all vaccinated individuals aged 6 months-64 years in the US received QIVc over QIVe, an estimated 2,379,395 additional symptomatic illnesses would have been prevented, with proportionate reductions in related complications.

Conclusions: Our analysis showed superior effectiveness of QIVc over QIVe in preventing test-confirmed influenza among persons aged 6 months-64 years, and provided the first demonstration of superiority in pediatric populations from 6 months of age. A Graphical Abstract is availible for this article.

Introduction: Antimicrobial resistance (AMR) is a substantial global health threat and economic burden. Vaccines reduce antibiotic use and prevent resistant infections, combating AMR. However, their economic and health benefits are often underestimated because economic analyses do not consider vaccines' broader impacts, such as effects on AMR. We conceptualize a framework for estimating the impacts of vaccination on AMR using pneumococcal conjugate vaccines (PCVs) as an example.

Methods: The proposed framework includes three pathways: population and pathogen, care, and health outcomes. Operationalizing this framework requires extensive detailed data, such as serotype distribution, disease incidence, resistance profile, antibiotic use, and treatment failure, derived from multiple sources, such as national surveillance systems, epidemiological studies, and hospital records, which are often unavailable. However, considering vaccines' impact on AMR is crucial because of potential future health and cost issues. Therefore, we adopted a simplified framework leveraging all available data related to antibiotic prescriptions and resistance to estimate the impact on critical outcomes.

Results: Routine PCV20 vaccination was estimated to prevent up to 23,509,406 antibiotic prescriptions and 14,050,115 antibiotic-resistant infections over 25 years compared to PCV13 and 12,087,128 antibiotic prescriptions and 7,245,908 antibiotic-resistant infections compared to PCV15, demonstrating the potential impact of PCV infant immunization on AMR cases and antibiotic prescriptions.

Conclusions: A simplified model can effectively incorporate critical AMR parameters for a more comprehensive evaluation of PCVs. Our framework also identifies key data gaps that should be addressed for future modeling efforts.

Introduction: International guidelines advocate obtaining urine cultures prior to antibiotic administration in hospitalized patients with suspected urinary tract infection (UTI). However, adherence remains suboptimal. The aim of this study was to evaluate the positivity rate of urine cultures following a single empiric antibiotic dose and to identify factors associated with post-antibiotic culture positivity.

Methods: A prospective observational study was conducted in an internal medicine ward between December 2019 and June 2024. Patients diagnosed with UTI who had both pre- and post-antibiotic urine cultures were included. Positivity rates of post-antibiotic urine cultures were assessed. Factors associated with culture positivity were examined using logistic regression.

Results: A total of 132 patients were included in the analysis (59% female; median age 79 years). Eighty-eight patients (67%) had a positive post-antibiotic urine culture. The positivity rate in patients with a sensitive and resistant uropathogen to the empirically administrated antibiotic was 58% and 100%, respectively. Independent predictors for urine culture positivity included older age (adjusted odds ratio [aOR] 1.04, confidence interval [CI] 1.01-1.07, p = 0.007) and recent urinary catheter use in the last 30 days (aOR 14.7, CI 1.66-128, p = 0.016). Culture sampling more than 9 h after antibiotic administration was a negative predictor for culture positivity (aOR 0.41, CI 0.18-0.96, p = 0.041).

Conclusion: Urine culture positivity remains high after a single antibiotic dose in hospitalized patients with UTI. In cases where pre-antibiotic urine cultures are missed, a timely post-antibiotic urine sampling remains clinically relevant for pathogen identification and appropriate antibiotic selection.

Introduction: Baloxavir marboxil (baloxavir), a cap-dependent endonuclease inhibitor, has been proven safe and efficacious against influenza and approved for the treatment of influenza in children aged ≥ 5 years in China. There were limited data on baloxavir in Chinese pediatric patients aged 1 to < 5 years with influenza. This study aimed to evaluate the safety, clinical efficacy, and virologic outcomes of baloxavir for treating influenza in this younger age group.

Methods: In this single-arm, multicenter trial, patients received a single oral dose of baloxavir (2 mg/kg for participants weighing < 20 kg, or 40 mg for participants weighing ≥ 20 kg to < 80 kg). The primary endpoint was safety. Efficacy, virology, and palatability endpoints were also assessed.

Results: All 100 enrolled children completed the study and received baloxavir. Adverse events were reported in 29 (29.0%) children, most commonly bronchitis and diarrhea. No death or adverse events leading to discontinuation occurred. Eighty children were included in the clinical efficacy and virologic assessment. The median [95% confidence interval (CI)] time to resolution of influenza signs and symptoms was 150.17 (90.23, NE) h. The median duration of fever was 38.65 (95% CI 25.32, 42.35) h. Infectious virus titers rapidly declined by day 2 post-dose. The proportion of subjects with a positive viral titer was reduced to 8.7% at this timepoint. Of the 100 children enrolled, more than 70% of children rated baloxavir as favorable in the palatability test.

Conclusion: A single, oral dose of baloxavir was well-tolerated in Chinese children aged 1 to < 5 years, with rapid influenza virus clearance and associated symptom alleviation, suggesting baloxavir was an important treatment option for Chinese pediatric patients with influenza.

Trial registration: The study was registered at the Chinese Clinical Trial Registry (ChiCTR) on March 14, 2025 (registration no. ChiCTR2500098911); Retrospectively registered.

Introduction: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still an ongoing public health threat. COVID-19 can be accompanied by prolonged symptoms, known as "long COVID", however, no pharmaceutical treatments are currently available for these symptoms. Lactococcus lactis strain Plasma (LC-Plasma; Lactococcus lactis subsp. lactis JCM 5805) directly activates human plasmacytoid dendritic cells (pDCs) and triggers antiviral immune responses. We hypothesized that LC-Plasma reduced SARS-CoV-2 viral load and eased symptoms in patients with mild COVID-19.

Methods: This PLATEAU study enrolled 100 patients with mild COVID-19 during Omicron BA.1 endemic, who were randomized into the LC-Plasma or placebo group in a 1:1 ratio and were observed for 14 days. The primary endpoint was change in total score of eight subjective symptoms (fatigue, anorexia, headache, cough, shortness of breath, chest pain, smell, and taste disturbance). Secondary endpoints included each symptom, SARS-CoV-2 viral load, and pDCs.

Results: The primary endpoint did not show between-group differences. However, the proportion of patients without smell and taste disturbances was significantly higher in the LC-Plasma group on day 13 (p = 0.030). The LC-Plasma group showed a significantly earlier decrease in SARS-CoV-2 viral load on day 4 (p < 0.001) and an increase in pDCs on day 8 (p = 0.0498). Mild adverse events, such as diarrhea, cough-variant asthma, and urticaria, occurred in three (5.9%) patients in the LC-Plasma group.

Conclusions: The intake of LC-Plasma in patients with mild COVID-19 activates pDC, decreases SARS-CoV-2 viral load earlier, and may improve smell and taste disorders more quickly. LC-Plasma could be a safe, inexpensive, and easily accessible tool for the treatment of mild COVID-19.

Trial registration: jRCTs071210097.