Infectious Diseases and Therapy最新文献

Introduction: The management of complicated Gram-positive bloodstream infections (cBSI) and infective endocarditis (IE) often requires prolonged intravenous therapy. Transition to oral therapy is frequently unfeasible because of resistance, drug interactions, or adherence concerns, increasing the risk of intravenous-related complications and healthcare burden. The pharmacokinetic profile and spectrum of oritavancin may enable effective treatment and early discharge. This study evaluated its effectiveness, safety, and impact on hospital resource use in patients with cBSI or IE.

Methods: We conducted a multicenter, retrospective, observational study across eight hospitals in Italy and Spain (April 2023-February 2025). Adult patients with Gram-positive cBSI (persistent/refractory BSI or prosthetic material) or IE (2023 modified Duke criteria) treated with ≥ 1 dose of oritavancin were included. Dosing was determined by the treating physicians. Data on outcomes, adverse events (AEs) and healthcare use were collected from medical records. Patients were followed for at least 6 months.

Results: Twenty-seven patients were included: 13 (48.1%) cBSI and 14 (51.9%) IE. Median age  was 73 years (IQR 65-81); 18 out of 27 (66.7%) were male; Charlson Comorbidity Index 6 (IQR 4-7). In cBSI, oritavancin was first-line in 6/13 (46.2%) and given in multiple doses in 8/13 (61.6%), median of 2 doses (IQR 2-2.5). Clinical success was 100%, with no recurrence or BSI-related mortality. In IE, Staphylococcus aureus was identified in 5 of 14 cases (35.7%), of which 40% were methicillin-resistant. Native valves were involved in 6/14 (42.8%), prosthetic valves in 6/14 (42.8%), cardiac devices in 2/14 (14.3%). Clinical success was achieved in 85.7% of patients with IE (12/14). Two AEs occurred: nausea and a non-fatal acute coronary syndrome in a patient with pre-existing ischemic heart disease. Oritavancin use reduced 369 hospital days with potential savings of approximately €4235 per patient.

Conclusions: Oritavancin may represent a safe, effective treatment option for selected patients with cBSI or IE, with advantages in outcomes, reduced hospital stay, and cost containment.

Introduction: Fecal microbiota, live-jslm (RBL) is the first single-dose, microbiota-based product approved by the US Food and Drug Administration and Health Canada to prevent recurrent Clostridioides difficile infection (rCDI) following standard-of-care antibiotics. The phase 3 PUNCH CD3-OLS study enrolled participants with numerous comorbidities and permitted inclusion of participants hospitalized due to rCDI. The safety and efficacy of RBL were evaluated in this subgroup analysis of hospitalized participants from PUNCH CD3-OLS.

Methods: The hospitalization subgroup included participants hospitalized for rCDI within 90 days prior to RBL administration. Participants received a single dose of RBL 24-72 h after completion of standard-of-care antibiotic treatment for rCDI. These exploratory analyses evaluated the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs), treatment success at 8 weeks, sustained clinical response at 6 months, and incidence of rehospitalization for rCDI during study participation.

Results: The hospitalization subgroup included 74 of 697 (10.6%) participants. Within 6 months following RBL administration, 47 (63.5%) and 350 (56.7%) participants in the hospitalization and nonhospitalization subgroups experienced TEAEs, respectively; most TEAEs were of mild to moderate severity. Serious TEAEs in the hospitalization subgroup were frequently related to preexisting conditions; none were related to RBL or its administration. Most participants (87.8% [65/74]) in the hospitalization subgroup were not rehospitalized within 6 months. Treatment success at 8 weeks was 62.5% (45/72) and 75.1% (449/598) among participants in the hospitalization and nonhospitalization subgroups, respectively. Of those achieving treatment success, 86.7% (39/45) and 91.3% (410/449) had sustained clinical response through 6 months in the hospitalization and nonhospitalization subgroups, respectively.

Conclusion: RBL was safe and effective in a subgroup of hospitalized participants in the PUNCH CD3-OLS study. Efficacy in this subgroup was slightly lower than in nonhospitalized participants, but rCDI-related rehospitalization remained rare.

Trial registration: NCT03931941.

Introduction: Haemophilus influenzae is a human-specific Gram-negative bacterium responsible for respiratory tract infection, sepsis, and meningitis. The study aimed to investigate the epidemiology, serotype distribution, and mechanisms of beta-lactam resistance among invasive H. influenzae strains isolated in Poland from 2018 to 2023.

Methods: Invasive H. influenzae isolates were received from patients with positive culture results from blood, cerebrospinal fluid (CSF), and pleural fluid. Sample data were obtained from the Polish laboratory surveillance system. For all isolates screening test for beta-lactam resistance was performed and the minimum inhibitory concentrations (MICs) of clinically relevant antibiotics were determined using antibiotic gradient strips. For isolates with inhibition zone P 1U < 12 mm (n = 133), whole genome sequencing (WGS) analysis was performed.

Results: Most strains of H. influenzae were isolated from blood (90.7%). Non-typeable Hinf (NTHi) strains were responsible for most invasive disease in all age groups and accounted for 85.7% (342/399) of all cases. Capsulated isolates constituted 14.3%; among them the most common serotype was type f (Hif; 64.9%), followed by serotypes: e (Hie; 19.3%), b (Hib; 14.0%), and d (Hid; 1.8%). Of the 399 isolates collected between 2018 and 2023, 15.8% and 1.0% were resistant to ampicillin and cefotaxime, respectively. Resistance to meropenem and ciprofloxacin using the meningitis breakpoint was detected in 4.3% and 1.8% strains, respectively. All isolates showed susceptibility to chloramphenicol. Resistance to rifampicin characterized 3.8% of isolates tested. The Cefinase test revealed beta-lactamase production in 8.8% of isolates.

Conclusions: In our study NTHi predominated among invasive cases across all age groups, especially among elderly patients, similarly to other countries. β-Lactam resistance among studies strains has remained stable over the years. Recently, however, resistance to third-generation cephalosporins has emerged. Continuous surveillance and a rational antibiotic policy are essential to address H. influenzae resistance.

Introduction: This study evaluated the effectiveness of Moderna's updated mRNA-1273 vaccine targeting the KP.2 variant, compared to people who did not receive any 2024-2025 COVID-19 vaccine, in preventing COVID-19-associated hospitalizations and medically-attended COVID-19 among adults aged ≥ 18 years in the United States during the 2024-2025 season.

Methods: Data were extracted from linked administrative healthcare claims and electronic health records (EHR) for vaccinations from 23 August 2024 through 23 April 2025 and followed through 30 April 2025. We conducted a retrospective matched cohort study with propensity score weighting to adjust for differences between groups to assess vaccine effectiveness (VE) against COVID-19 outcomes. VE was calculated as 1 minus the hazard ratio (HR) from Cox proportional hazards models.

Results: Overall, 596,248 mRNA-1273 KP.2 vaccine recipients were matched 1:1 to unexposed adults. The mean (standard deviation) age was 63 (17) years, with more than half of the population being 65 years or older. Approximately 70% of individuals had an underlying medical condition making them high-risk for severe outcomes for COVID-19. VE was 52.8% [95% confidence interval (CI) 34.8%, 65.8%] against COVID-19-related hospitalization and 39.4% (35.0%, 43.5%) against medically-attended COVID-19 over a median follow-up of 55 (interquartile range 32-77) days in an interim analysis. The VE was sustained throughout the entire study period and shown to be 45.2% (37.7%, 51.8%) against COVID-19-related hospitalizations and 33.1% (30.6-35.4%) against medically-attended COVID-19 over a median follow-up of 127 (interquartile range 84-173) days.

Conclusion: The mRNA-1273 KP.2 vaccine demonstrated significant incremental effectiveness in preventing hospitalization with COVID-19 and medically-attended COVID-19 in adults during the 2024-2025 season to date. The VE was sustained with longer median follow up time. These findings support ongoing vaccination efforts to mitigate the public health impact of COVID-19.

Introduction: This study aims to deliver contemporary, population-based estimates of herpes zoster (HZ) incidence, temporal trends, complications, healthcare utilisation and direct costs among general adults and adults with increased-risk conditions.

Methods: A retrospective cohort study using the Yinzhou Integrated Health Platform (2015-2021; China) was performed. Incident HZ was ascertained after a 1-year washout; increased-risk conditions were pre-specified (immunocompromising/autoimmune). We calculated age-/sex-standardised incidence, assessed trends with joinpoint regression and summarised HZ-related outpatient visits, hospitalisations and direct medical costs [Chinese yuan (¥) and US dollars ($)].

Results: Among 5.42 million person-years, including 790,410 subjects, 25,855 incident HZ events were identified. Overall incidence was 4.77/1000 person-years (PY) [95% confidence interval (CI) 4.71-4.83] and 16.13/1000 PY (95% CI 15.25-17.06) in increased-risk adults [incidence rate ratio (IRR) 3.44 versus in adults without immunocompromising conditions or autoimmune diseases (AIDs)]. Incidence rose with age (peak 70-79 years overall; 60-69 years increased-risk) and was higher in women. Postherpetic neuralgia (PHN) was the most frequent complication (8.96% overall; 10.88% increased-risk). Standardised incidence increased from 4.67 to 7.51/1000 PY during 2015-2021 [annual percentage change (APC) 7.94%], with a steep rise to 2019 and plateau thereafter. Hospitalisation among incident HZ was 1.35%. Mean direct cost per episode was Chinese yuan (¥)625.52 [US dollars ($)94.35] for outpatients and ¥8854.03 ($1335.45) for inpatients; increased-risk outpatients incurred higher mean costs (¥1205.47, $181.82). Across strata, complications - especially PHN - were associated with more visits and higher expenditure.

Conclusions: HZ imposes a rising, age- and risk-concentrated burden in Chinese adults, with PHN being the principal driver of resource use and costs. These real-world estimates support prioritising zoster vaccination for adults ≥ 50 years and clinically vulnerable groups, and integrating HZ surveillance and management within chronic-disease programmes.

Introduction: Detailed characterization of the antibody profile induced by SARS-CoV-2 mRNA vaccines has shown that repeat dosing boosts all immunoglobulin G (IgG) subclasses, with a notable emergence of antigen-specific IgG4 antibodies. While the IgG4 subclass is traditionally associated with limited Fc-effector functions, its role in SARS-CoV-2 mRNA vaccine-induced immunity remains unclear.

Methods: This study tracked IgG subclass dynamics, IgG Fc-mediated functions, and neutralization following immunization with two or three doses of Moderna SARS-CoV-2 mRNA vaccine (mRNA-1273) in healthy adults.

Results: We observed robust spike-specific IgG1 and IgG3 responses after the primary series (two doses) and booster dose, with a significant increase in IgG4 responses after repeated dosing. Despite this rise in spike-specific IgG4 antibodies, strong Fc-effector functions were maintained at the overall IgG level, including antibody-dependent cellular phagocytosis, antibody-dependent neutrophil phagocytosis, and antibody-dependent complement deposition, with no antagonism from IgG4 antibodies. Additionally, IgG4 antibodies exhibited enhanced affinity and potent neutralization, complementing IgG1-driven responses.

Conclusions: These findings suggest that elevated IgG4 responses did not antagonize overall Fc-mediated effector mechanisms, indicating that mRNA-1273 induces a multi-subclass antibody response that preserves antiviral functionality.

Trial registration: NCT04470427.

Introduction: This study aimed to investigate whether droplet digital polymerase chain reaction (ddPCR) assay can be integrated with antimicrobial stewardship for rapid diagnosis to improve clinical outcomes in patients with suspected bloodstream infections (BSIs). We also explored whether combining ddPCR assay with procalcitonin (PCT) could better guide antibiotic discontinuation in patients with suspected BSIs.

Methods: This prospective observational study was conducted in Zhejiang Provincial People's Hospital from April 2019 to October 2023. Antimicrobial drug combinations were categorized as appropriate or inappropriate based on the findings of the ddPCR assay. Propensity score matching (PSM) was conducted to address possible confounding variables. The primary outcome was 28-day all-cause mortality.

Results: A total of 703 patients were evaluated for the consistency of pathogens detected by ddPCR with those covered by the initial antibiotic regimen (IAR). Among these patients, 355 received appropriate IAR, 256 were adjusted for inappropriate IAR, and 92 were unadjusted for inappropriate IAR. A significant difference in 28-day mortality among the three cohorts was observed before and after PSM (P ≤ 0.002). Multivariate Cox regression analysis showed that IAR adjustment [inappropriate IAR unadjusted as reference, appropriate IAR: hazard ratio (HR) = 0.47; P < 0.001; inappropriate IAR adjusted: HR = 0.54; P < 0.001] remained independent predictors for 28-day mortality. In addition, in a subgroup analysis of 257 patients receiving > 7 days of antibiotic therapy and antibiotic discontinuation, the 28-day mortality using the ddPCR assay combined with PCT-guided antibiotic discontinuation was significantly lower (12.0 vs. 37.3 vs. 39.6%; P < 0.001) than that of those guided by ddPCR assay or PCT alone.

Conclusions: Integrating a ddPCR assay for rapid diagnosis with antibiotic stewardship could improve the prognosis in patients with BSIs, not only by guiding antibiotic regimen adjustment but also by making decisions on antibiotic discontinuation in conjunction with PCT.

Trial registration: ChiCTR, ChiCTR2600116655.

Introduction: Respiratory syncytial virus (RSV) is the leading cause of infant hospitalizations in the United States, with a significant seasonal impact on healthcare resources. Long-acting monoclonal antibodies (mAbs), nirsevimab and clesrovimab, provide protection against RSV-related lower respiratory tract disease (LRTD); however, no head-to-head comparisons are available to inform clinical decision-making.

Methods: We developed a cost-effectiveness analysis framework to perform an indirect comparison of nirsevimab and clesrovimab for RSV prevention, consistent with CDC guidance for pre-season catch-up and in-season immunization for infants born outside and during the RSV season, respectively. Pharmacokinetic data were used to model the duration of cumulative efficacy over time. A 150-day duration was evaluated for nirsevimab, while three scenarios were assessed for clesrovimab (100-, 120-, and 150-day durations). A cost-utility analysis evaluated health outcomes, healthcare resource use, and associated costs.

Results: The modeled prediction suggests nirsevimab demonstrated greater clinical benefit and more favorable economic outcomes compared to clesrovimab across all protection duration scenarios. Nirsevimab use consistently resulted in reduced cases of RSV medically attended (MA)-LRTDs and therefore direct and indirect costs associated with RSV management. From a cost-effectiveness perspective, nirsevimab was dominant (i.e., more effective and less costly) compared to clesrovimab in all analyzed scenarios. Additional scenario analyses leveraging trial data differentiated by infant gestational age for both nirsevimab and clesrovimab and alternative RSV seasonality demonstrated that model conclusions remain stable. These analyses confirmed the robustness of our findings, with nirsevimab consistently offering greater value.

Conclusions: Our findings predict that nirsevimab is economically dominant over clesrovimab while providing greater clinical protection against RSV-related disease in these scenarios. These results are robust to sensitivity analyses with nirsevimab consistently estimated as reducing healthcare resource utilization and total costs compared to clesrovimab across assumptions related to clesrovimab duration of cumulative efficacy as well as variation in key model parameters.

Introduction: Tuberculosis (TB) affects over 10 million people worldwide annually, is difficult to treat, and is a major cause of death. The M72/AS01_E candidate vaccine is the first vaccine in over 100 years with the potential to protect adolescents/adults. To prepare for the introduction of the vaccine and ensure adequate manufacturing capacity, global vaccine demand must be carefully estimated in advance.

Methods: A global demand forecasting model was developed that considered demand factors such as TB burden, external funding, anticipated interest, and country vaccine adoption capabilities, which determined assumptions for the timing and implementation approach of vaccine introduction. Assuming initial M72/AS01_E regulatory approval in 2029, demand for routine vaccination and catch-up campaigns was forecasted through to 2045.

Results: Adoption of M72/AS01_E was projected to begin in South Africa in 2029, expanding to 89 countries by 2039. In the base-case forecast, demand reached a steady state of around 56 million doses per year by 2036, and decreased to around 43 million doses per year following licensure of another global TB vaccine, assumed in 2037. Seven countries accounted for 61% of demand, and approximately half of all demand was from Gavi-eligible countries (Gavi, the Vaccine Alliance). In scenario analyses, demand increased by 43% (peaking at 79 million in 2036), assuming higher efficacy and more available funding, and decreased by 34%, assuming narrower, delayed policy recommendations and less available funding. Key drivers of global demand included adoption timing, target population, and coverage.

Conclusions: M72/AS01_E has the potential to reduce the TB burden worldwide. Successful vaccine introduction requires early and coordinated planning, with detailed demand forecasting refined over time. The model will be updated as new data and country implementation plans emerge. To avoid access delays, continued collaboration among key stakeholders, including vaccine suppliers, and early visibility on policy recommendations and domestic and donor funding availability will be critical in the coming years.