Infectious Diseases and Therapy最新文献

Introduction: This phase IV study aimed to evaluate the safety of the 23-valent pneumococcal polysaccharide vaccine (PPV23) in individuals aged 2 years and older through active and passive surveillance.

Methods: Safety data were collected from May 2022 to March 2024 through 28-day post-vaccination active surveillance via active follow-up and 1-year passive surveillance via the Chinese National Adverse Events Following Immunization (AEFI) Information System (CNAEFIS). Adverse drug reactions (ADRs) via active follow-up and AEFIs via CNAEFIS were analyzed by age, health status, and co-administration status.

Results: A total of 19,267 participants received a single dose of PPV23, including 2977 under active surveillance and 16,290 under passive surveillance. In active surveillance, the overall incidence of ADRs was 1.81%, mostly mild and self-limiting, with rates of 1.76% in children (2-17 years), 2.28% in adults (18-59 years), and 1.67% in older adults (60 years and older). The incidence was 1.79% among healthy participants and 1.92% among participants with underlying medical conditions, and the incidence was 1.01% following PPV23 alone and 4.96% after co-administration with influenza vaccines. Passive surveillance identified 60 AEFI case reports (368 per 100000 doses), all occurring within 7 days of vaccination. No serious adverse event or serious AEFI were reported.

Conclusion: The PPV23 showed a favorable safety profile in all age groups, regardless of health status or co-administration with influenza vaccines. These findings support the use of PPV23 and provide evidence for its co-administration with influenza vaccines.

Clinicaltrials:

Gov identifier: NCT07071701. Retrospectively registered.

Introduction: The survival benefit of early antibiotic administration in septic shock is well established. In contrast, for sepsis without shock, the current Surviving Sepsis Campaign (SSC) guidelines recommend initiating antibiotics according to the likelihood of infection. Given the persistent challenges in accurately diagnosing sepsis, there is a need to identify patient characteristics to guide antimicrobial timing in this population.

Methods: In this cohort study, we included adult intensive care unit (ICU) patients meeting Third International Consensus Definitions for Sepsis (Sepsis-3) criteria without shock, identified from 24 hours before to 48 hours after ICU admission, who received antibiotics within 0-12 hours after sepsis diagnosis. The primary exposure was shorter time-to-antibiotics (≤ 3 hours), and the primary outcome was 28-day mortality. Heterogeneity of treatment effect (HTE) was evaluated with conventional subgroup, risk-based, and effect-based analyses.

Results: A total of 8400 patients were included, of whom 2891 (34.4%) received antibiotics within 3 hours and emergency admission was the most common admission type (64.2%). Baseline characteristics were well balanced after overlap weighting. Shorter time-to-antibiotics was not associated with 28-day mortality in the overall population (median value for the posterior distribution of the odds ratio (OR) 0.92; 95% credible interval (CrI) 0.79-1.06). In conventional subgroups, the impact of shorter time-to-antibiotics on 28-day mortality varied substantially between patients aged ≥ 78 years and other age subgroups (median value for the posterior distribution of the OR 0.73; 95% CrI 0.55-0.94). In risk-based analysis, patients in the third quartile of baseline mortality risk exhibited the most favorable estimated association with shorter time-to-antibiotics (median value for the posterior distribution of the OR 0.65; 95% CrI 0.46-0.87). In effect-based analysis, patients with advanced age, higher Charlson Comorbidity Index (CCI), higher Acute Physiology Score III (APS III), or acute liver dysfunction were identified as having greater benefit from shorter time-to-antibiotics.

Conclusion: Among ICU patients with sepsis without shock, those who are older, have higher CCI or APS III, or acute liver dysfunction are more likely to benefit from shorter time-to-antibiotics.

Introduction: Neutralizing antibody titers are recognized as an acceptable surrogate efficacy endpoint for immunobridging next-generation monoclonal antibodies (mAbs) to those with demonstrated clinical efficacy for the prevention of COVID-19. However, titers measured at early time points after dosing overestimate levels required for clinical protection. Long-term efficacy data are limited due to continued evolution of SARS-CoV-2 and loss of activity of previously effective mAbs against emerging variants. We aimed to develop a predictive tool for efficacy using neutralizing titers to provide a framework for dose selection, target efficacy, and immunobridging of mAbs for the prevention of COVID-19.

Methods: Drug concentration and clinical efficacy data collected over 12 months following pemivibart administration in the phase 3 CANOPY trial were used to develop a Cox proportional hazards model with time-varying covariate as a statistical immune correlates of protection model. The time-varying covariate was estimated serum virus neutralizing antibody activity, estimated at 2-week intervals by integrating drug concentration with weighted average IC₅₀ (half-maximal inhibitory concentration) values of the circulating variant population. Clinical efficacy was predicted in immunocompromised and non-immunocompromised populations.

Results: Efficacy increased with antibody titer in a non-linear manner, with smaller incremental gains at higher concentrations. Predicted efficacy was lower at all titer levels in the immunocompromised cohort. Model-derived estimates aligned well with observed infection outcomes and external analyses, supporting model validity. A titer of 1:500 predicted an estimated efficacy of 50% (immunocompromised) and 70% (non-immunocompromised).

Conclusion: The Cox model enables evaluation of suitable neutralizing titer targets to guide dosing, predict estimated clinical benefit for related mAbs derived from the same platform, and support immunobridging in both immunocompromised and non-immunocompromised populations.

Trial registration: ClinicalTrials.gov identifier, NCT06039449.

Introduction: Outpatient parenteral antimicrobial therapy (OPAT) enables effective infection management outside hospital settings, offering clinical and economic benefits. While widely adopted internationally, its implementation in Italy remains fragmented. This study aimed to systematically map the use of OPAT in Italy to identify research and policy priorities.

Methods: A scoping review was conducted following the Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews guidelines. The protocol was registered on the Open Science Framework ( https://doi.org/10.17605/OSF.IO/GX8S6 ) in August 2025. Searches were performed across PubMed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Scopus. Eligible studies included primary research on OPAT in Italy, with no restrictions on publication date or language. Data extraction focused on study characteristics, OPAT indications, antimicrobial agents, delivery models, and outcomes.

Results: Twenty-three studies were included, mostly observational and single-center, published between 2000 and 2025. OPAT was primarily delivered at home or in infusion centers. The most frequent indications were infections of bone and joint, skin and soft tissue, and the respiratory tract. Ceftriaxone was the most used antimicrobial. Delivery was mainly intravenous, often via elastomeric pumps and peripheral or central venous access. Reported outcomes were generally favorable, with cure or improvement rates exceeding 90% in several studies. Adverse events were infrequent, mostly associated with drug reactions or catheter-related complications. Patient satisfaction was consistently high. Economic evaluations were limited but suggested cost savings primarily driven by reductions in hospital stays.

Conclusions: OPAT is feasible and increasingly used in Italy, but remains inconsistently implemented across regions. Broader adoption would benefit from national guidance, standardized protocols, and integrated stewardship frameworks. Future research should address comparative and cost-effectiveness, as well as equitable access, to support systematic scale-up aligned with national health priorities on antimicrobial resistance and community-based care.

Introduction: Candidemia is a notable cause of morbidity and mortality in critically ill children. The Pediatric (Paed)-EQUAL scale, which includes 11 clinical and microbiological assessment parameters, was recently developed to improve guideline compliance in pediatric patients with candidemia. The aim of our study was to evaluate compliance with the Paed-EQUAL scale in pediatric patients with candidemia and to demonstrate its relationship with survival.

Methods: We retrospectively analyzed the clinical and microbiological characteristics and compliance with the Paed-EQUAL scale parameters of patients aged 1 month to 18 years who were diagnosed with candidemia and admitted to our pediatric intensive care unit over a 10-year period. Among the 117 candidemia cases identified, 103 were included in the study. We evaluated the associations between survival and various parameters, including the Paed-EQUAL score and candidemia-related clinical and microbiological characteristics.

Results: The 30-day mortality rate in our cohort was 17.5%. The Paed-EQUAL score had a significant discriminatory ability for identifying mortality outcomes. In the entire cohort, patients with a score of ≥ 16.5 had a greater likelihood of survival (AUC 0.742; p = 0.001). Separate analyses for patients with and without central venous catheters (CVCs) revealed that the discriminatory performance increased to an excellent level (AUC 0.913) among those without CVCs, which was based on a lower optimal cutoff (≥ 12.5). Multivariable regression revealed that the presence of breakthrough candidemia was associated with 10.5-fold greater odds of mortality (OR 10.52, 95% CI 1.66-66.7; p = 0.013), whereas each 1-point increase in the Paed-EQUAL score was associated with 1.4-fold greater odds of survival (OR 0.703, 95% CI 0.53-0.89; p = 0.004). Individual Paed-EQUAL components had no significant predictive role in assessing mortality risk.

Conclusion: The present study revealed that the Paed-EQUAL score can predict mortality in pediatric patients with candidemia. Patients with a Paed-EQUAL score of ≥ 16.5 had significantly higher rates of survival.

Introduction: Infections caused by metallo-β-lactamase-producing Enterobacterales offer limited therapeutic options. Aztreonam-avibactam (ATM-AVI) provides a promising alternative, but its approved intermittent regimen is complex and can lead to substantial drug waste.

Methods: We describe a case of mastoiditis with a retrotympanic abscess due to OXA-48- and NDM-1-producing Klebsiella pneumoniae, managed with continuous infusion (CI) of ATM-AVI after a full-vial loading dose, supported by therapeutic drug monitoring (TDM) and whole-genome sequencing (EPISEQ CS V2.0, bioMérieux).

Results: A 35-year-old man previously treated abroad for meningitis and brain abscesses presented with residual deep-seated infection caused by OXA-48- and NDM-1-producing K. pneumoniae. After initial treatment with ceftazidime-avibactam plus aztreonam, therapy was switched to ATM-AVI using a full-vial loading dose followed by CI. TDM demonstrated sustained plasma levels of both drugs, and the patient improved without adverse events.

Conclusion: CI of ATM-AVI following a high loading dose was feasible, safe, and allowed optimized pharmacokinetic/pharmacodynamic (PK/PD) exposure while preventing drug wastage. Larger studies are warranted to determine the clinical utility of CI ATM-AVI across different MIC ranges.

Invasive meningococcal disease (IMD) in older adults frequently presents with atypical clinical manifestations, including bacteremic pneumonia, often without classical meningeal signs or sepsis, which presents clinicians with diagnostic challenges, and may delay treatment, which contributes to the high mortality observed in older adults. Within the broader resurgence of IMD observed since relaxation of quarantine measures introduced to mitigate the impact of the COVID-19 pandemic, there has been a notable increase in reporting of such atypical cases. The aim of this review is to summarize epidemiological, diagnostic, and treatment aspects of non-meningeal forms of IMD in older patients, with a focus on meningococcal pneumonia. By convention, laboratory confirmation requires N. meningitidis detection by culture, polymerase chain reaction (PCR), or antigen detection. In most cases, presentation of meningococcal pneumonia is similar to that of other forms of community-acquired pneumonia, and cerebrospinal fluid sampling may be non-informative. This places a premium on early blood culture for N. meningitidis, allied with testing of respiratory samples (e.g., broncho-alveolar washes). Many cases are linked to isolates of serogroups Y and W. When confirmed, treatment with third-generation cephalosporins is generally preferred. Chemoprophylaxis and vaccination of close contacts is essential for controlling onward meningococcal disease transmission and prevention of further cases.

Antibiotic discovery and antibiotic prescribing represent two domains that both stand to benefit from artificial intelligence (AI)-driven progress in the near future. In this article, we discuss these parallel advances and the potential future synergy between AI-enabled antibiotic discovery and AI-assisted antibiotic prescribing. Although multiple challenges remain before these two domains meaningfully converge, their integration could amplify the strengths of each: discovery pipelines generating broader, more diverse classes of antibacterial agents, and prescribing tools capable of matching these agents to individual patients with unprecedented precision. Such a scenario could transform antibiotic therapy by enabling AI-supported, patient-specific treatment decisions while reinforcing the principles of precision medicine and antimicrobial stewardship.

Introduction: Respiratory syncytial virus (RSV) is an important cause of hospitalizations among adults. Following bivalent respiratory syncytial virus prefusion F (RSVpreF) vaccine licensure and implementation, two studies have documented population-level reductions in RSV hospitalizations in the United Kingdom (UK), ranging from 30% to 62% in England and Scotland, respectively. Separately, vaccine effectiveness (VE) studies have been conducted in a number of settings. The question arises: Is there a relationship between these population-level reductions in RSV hospitalizations and real-world VE estimates from the first season post-implementation of bivalent RSVpreF, and do the impact findings reflect what would be expected from the VE estimates?

Methods: Publicly available estimates for end-of-season-1 (EOS1) bivalent RSVpreF VE against RSV-related hospitalization were identified. Using these VE estimates, the expected vaccine impact across all potential vaccine coverage values was calculated using the formula impact = VE * uptake. We additionally estimated expected VE based on the impact findings from the RDD analyses.

Results: Six real-world studies evaluating bivalent RSVpreF VE were identified from the United States, UK, and Denmark; they documented 67-91% bivalent RSVpreF VE against RSV-related hospitalizations. Calculated impact using these six VE estimates closely aligned with the measured results estimated from the UK analyses. VEs calculated in turn from impact estimates ranged from 91% [Scotland] to 76% [England], closely aligning with expected results.

Conclusions: These early results indicate that the extent of expected population-level impact achieved can be reliably predicted from VE studies and national coverage data. Bivalent RSVpreF use can have a substantial public health and economic impact by reducing RSV-related hospitalizations, as seen in this initial UK vaccination program. Protection of older adults from severe RSV disease is off to a promising start and implementation efforts to boost vaccine uptake should be a priority for health care workers, public health practitioners, and policymakers.

Introduction: The molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) impact transmission, clinical presentation, and treatment. Contemporary data on the molecular epidemiology of MRSA causing healthcare-associated (HA) infections in Latin America are scarce. In this study, we aimed to assess the molecular epidemiology, virulence genes, and antimicrobial susceptibility of MRSA bloodstream infections (BSI) isolates from Brazil.

Methods: A multicenter, prospective study in 14 Brazilian hospitals was conducted from August/2022 to August/2023. MRSA isolates recovered from HA-BSIs were sent to a central laboratory for whole-genome sequencing (WGS) and antimicrobial susceptibility testing.

Results: Of 255 S. aureus, 66 (25.9%) were MRSA, and 47 were submitted to WGS. The most frequent clonal complex (CC) was CC5 (n = 34, 72.3%), mostly of sequence types (ST) 105 (19/34; 55.9%) and ST5 (6/34; 17.6%). ST105(CC5)-SCCmecII-t002 was the commonest strain (10/47, 56.2%), detected in three of four studied regions, followed by the ST8(CC8)-SCCmecIV strains with distinct spa types (9/47; 19.2%). Three new MLST alleles were discovered, resulting in new ST designations 10,174, 10,175, and 10,176. Furthermore, the resulting phylogeny revealed three well-defined clades. Twenty-eight virulence genes were detected. All isolates were susceptible to vancomycin, linezolid, and ceftaroline, while susceptibility to daptomycin and delafloxacin was 88.9% and 51.2%, respectively.

Conclusions: The recently reported ST105(CC5)-SCCmecII-t002 clone has disseminated in hospitals from different Brazilian regions, together with other lineages that have been previously associated with community-associated infections, composed a new molecular landscape of MRSA causing HA BSIs in Brazil.